The DOI matches its Crossref record; 122 of the 125 references it cites were found in a registry or an index; 46 of the 155 sources its claims cite were checked for support.
Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association
Open accessAbstract
Hypertriglyceridemia (triglycerides 200-499 mg/dL) is relatively common in the United States, whereas more severe triglyceride elevations (very high triglycerides, ≥500 mg/dL) are far less frequently observed. Both are becoming increasingly prevalent in the United States and elsewhere, likely driven in large part by growing rates of obesity and diabetes mellitus. In a 2002 American Heart Association scientific statement, the omega-3 fatty acids (n-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were recommended (at a dose of 2-4 g/d) for reducing triglycerides in patients with elevated triglycerides. Since 2002, prescription agents containing EPA+DHA or EPA alone have been approved by the US Food and Drug Administration for treating very high triglycerides; these agents are also widely used for hypertriglyceridemia. The purpose of this advisory is to summarize the lipid and lipoprotein effects resulting from pharmacological doses of n-3 FAs (>3 g/d total EPA+DHA) on the basis of new scientific data and availability of n-3 FA agents. In treatment of very high triglycerides with 4 g/d, EPA+DHA agents reduce triglycerides by ≥30% with concurrent increases in low-density lipoprotein cholesterol, whereas EPA-only did not raise low-density lipoprotein cholesterol in very high triglycerides. When used to treat hypertriglyceridemia, n-3 FAs with EPA+DHA or with EPA-only appear roughly comparable for triglyceride lowering and do not increase low-density lipoprotein cholesterol when used as monotherapy or in combination with a statin. In the largest trials of 4 g/d prescription n-3 FA, non-high-density lipoprotein cholesterol and apolipoprotein B were modestly decreased, indicating reductions in total atherogenic lipoproteins. The use of n-3 FA (4 g/d) for improving atherosclerotic cardiovascular disease risk in patients with hypertriglyceridemia is supported by a 25% reduction in major adverse cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With EPA Intervention Trial), a randomized placebo-controlled trial of EPA-only in high-risk patients treated with a statin. The results of a trial of 4 g/d prescription EPA+DHA in hypertriglyceridemia are anticipated in 2020. We conclude that prescription n-3 FAs (EPA+DHA or EPA-only) at a dose of 4 g/d (>3 g/d total EPA+DHA) are an effective and safe option for reducing triglycerides as monotherapy or as an adjunct to other lipid-lowering agents.
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Claims the paper makes
50 No full text of the sources · 31 Own interpretation · 18 Partly supported · 13 No basis given · 7 Supported so far · 5 Not supported · 5 Couldn’t confirm · 5 Sources not found · 4 Supported · 4 Not checked yet · 2 Own method · 1 Mixed support · 1 Own result · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Non-HDL-C decreased by 4% to 6% in all 3 groups at 12 and 52 weeks”
§ e673 > COMPARISON OF EPA+DHA VERSUS EPA-ONLY AGENTS ON LIPIDS AND LIPOPROTEINS IN INDIVIDUALS WITH HTG
What the sources say
- Disputedcites [52] 52. Shearer GC, Pottala JV, Hansen SN, Brandenburg V, Harris WS. Effects of prescription niacin and omega-3 fatty acids on lipids and vascular func- tion in metabolic syndrome: a randomized controlled trial. J Lipid Res. 2012;53:2429-2435. doi: 10.1194/jlr.P022392 sourceExperimental — accuracy not yet measured
The Methods (Study design; page unavailable) describe four groups treated for 16 weeks, not three groups assessed at 12 and 52 weeks. Results (Table 3; page unavailable) report non-HDL-C decreases in all four groups, but as changes in mg/dL (−5.9, −23, −11, and −7.3), not a 4%–6% decrease in three groups at those time points. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“Non-HDL-C decreased by 5% to 7% in the 3 largest studies of 4 g/d O3AEE, 22,33,34”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [22] 22. Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. Eicosapentaenoic acid ethyl ester (AMR101) therapy in pa- tients with very high triglyceride levels (from the Multi-center, plAcebo- controlled, Randomized, double-blINd, 12-week study with an open- label Extension [MARINE] trial). Am J Cardiol. 2011;108:682-690. doi: 10.1016/j.amjcard.2011.04.015 source
- Supportedcites [33] 33. Bays HE, McKenney J, Maki KC, Doyle RT, Carter RN, Stein E. Effects of prescription omega-3-acid ethyl esters on non-high-density lipoprotein cholesterol when coadministered with escalating doses of atorvastatin. Mayo Clin Proc. 2010;85:122-128. doi: 10.4065/mcp.2009.0397 source
The Efficacy section reports that 4 g/d of prescription omega-3-acid ethyl esters plus atorvastatin reduced median non-HDL-C by 6.5 percentage points more than placebo plus atorvastatin during the 10-mg atorvastatin phase. That supports the 5%–7% figure for this study; the other two cited studies are not being attributed to this source alone. (LLM, conf=0.88)
- Disputedcites [34] 34. Skulas-Ray AC, Kris-Etherton PM, Harris WS, Vanden Heuvel JP, Wagner PR, West SG. Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia. Am J Clin Nutr. 2011;93:243-252. doi: 10.3945/ajcn.110.003871 sourceExperimental — accuracy not yet measured
The study used four 1-g omega-3 fatty acid ethyl ester capsules per day at its higher dose (Design and interventions). Its lipid table (DISCUSSION; page not provided) reports non-HDL-C of 166.4 mg/dL with placebo and 164.7 mg/dL at the higher dose—about a 1% decrease, not 5% to 7%. The table also reports no significant treatment effect (P = 0.54). (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“The placebo-corrected LDL-C effect of 4 g/d IPE was -6% (control, 8.8%; active, 2%).36”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Disputedcites [36] 36. Metkus TS, Timpone J, Leaf D, Bidwell Goetz M, Harris WS, Brown TT. Omega-3 fatty acid therapy reduces triglycerides and interleu- kin-6 in hypertriglyeridemic HIV patients. HIV Med. 2013;14:530-539. doi: 10.1111/hiv.12046 sourceExperimental — accuracy not yet measured
The Methods (Treatment; page unavailable) identify the active treatment as Lovaza, a mixture of EPA and DHA, not IPE. The Results (Effect of O3A ethyl esters on lipid parameters; page unavailable) report no between-group difference in LDL cholesterol and do not report the claimed −6%, 8.8%, or 2% LDL-C figures. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Six published trials in which 3 to 4 g/d n-3 FA was administered to people with HTG not taking other lipidlowering medications were identified as meeting the inclusion criteria listed above.”
§ e673 > n-3 FA as Monotherapy
What the sources say
- Not checked — no full text of the sourcecites [28] 28. Roth EM, Bays HE, Forker AD, Maki KC, Carter R, Doyle RT, Stein EA. Prescription omega-3 fatty acid as an adjunct to fenofibrate therapy in hypertriglyceridemic subjects. J Cardiovasc Pharmacol. 2009;54:196-203. doi: 10.1097/FJC.0b013e3181b0cf71 source
- Not checked — no full text of the sourcecites [29] 29. Mackness MI, Bhatnagar D, Durrington PN, Prais H, Haynes B, Morgan J, Borthwick L. Effects of a new fish oil concentrate on plasma lipids and lipoproteins in patients with hypertriglyceridaemia. Eur J Clin Nutr. 1994;48:859-865. source
- Could not verifycites [33] 33. Bays HE, McKenney J, Maki KC, Doyle RT, Carter RN, Stein E. Effects of prescription omega-3-acid ethyl esters on non-high-density lipoprotein cholesterol when coadministered with escalating doses of atorvastatin. Mayo Clin Proc. 2010;85:122-128. doi: 10.4065/mcp.2009.0397 sourceExperimental — accuracy not yet measured
The Patients and Methods section describes eligibility for this paper’s own trial, and its treatment-flow figure shows omega-3 fatty acids given with atorvastatin. Our copy does not report identifying six published monotherapy trials that met inclusion criteria; searches for that wording and for six omega-3 monotherapy trials found no such passage. Page numbers were not available in the indexed passages. (LLM, conf=0.75)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“deed, such an effect on LDL particle size is supported by the results of more recent studies of HTG.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [24] 24. Sadovsky R, Kris-Etherton P. Prescription omega-3-acid ethyl esters for the treatment of very high triglycerides. Postgrad Med. 2009;121:145-153. doi: 10.3810/pgm.2009.07.2020 source
- Supportedcites [25] 25. Dunbar RL, Nicholls SJ, Maki KC, Roth EM, Orloff DG, Curcio D, Johnson J, Kling D, Davidson MH. Effects of omega-3 carboxylic acids on lipoprotein particles and other cardiovascular risk markers in high-risk statin-treated patients with residual hypertriglyceridemia: a random- ized, controlled, double-blind trial. Lipids Health Dis. 2015;14:98. doi: 10.1186/s12944-015-0100-8 source
The Lipoprotein particle sizes and concentrations section reports that LDL particle size increased significantly with both omega-3 carboxylic acid doses versus control in statin-treated patients with residual hypertriglyceridemia. It also reports an inverse correlation between changes in triglycerides and LDL particle size. Page numbers are not provided in our copy. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [26] 26. Maki KC, Bays HE, Dicklin MR, Johnson SL, Shabbout M. Effects of prescription omega-3-acid ethyl esters, coadministered with atorv- astatin, on circulating levels of lipoprotein particles, apolipoprotein CIII, and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia. J Clin Lipidol. 2011;5:483-492. doi: 10.1016/j.jacl.2011.09.001 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“In this study and another of O3AEE, there was a modest increase in LDL particle size.”
§ e673 > n-3 FA Added to Other Lipid-Lowering Therapies
What the sources say
- Supportedcites [25] 25. Dunbar RL, Nicholls SJ, Maki KC, Roth EM, Orloff DG, Curcio D, Johnson J, Kling D, Davidson MH. Effects of omega-3 carboxylic acids on lipoprotein particles and other cardiovascular risk markers in high-risk statin-treated patients with residual hypertriglyceridemia: a random- ized, controlled, double-blind trial. Lipids Health Dis. 2015;14:98. doi: 10.1186/s12944-015-0100-8 source
The Lipoprotein particle sizes and concentrations section reports significantly increased LDL particle size with both OM3-CA doses; Table 1 shows small increases of 0.3% and 0.6%. The Discussion also reports increased LDL particle size in studies of omega-3 acid ethyl esters. The cited paper therefore supports the statement about its own study and another O3AEE study. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [26] 26. Maki KC, Bays HE, Dicklin MR, Johnson SL, Shabbout M. Effects of prescription omega-3-acid ethyl esters, coadministered with atorv- astatin, on circulating levels of lipoprotein particles, apolipoprotein CIII, and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia. J Clin Lipidol. 2011;5:483-492. doi: 10.1016/j.jacl.2011.09.001 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In these studies, DHA consistently increased HDL-C compared with EPA, 60,61”
§ e673 > EFFECTS OF EPA-ONLY VERSUS DHA-ONLY ON LIPIDS AND LIPOPROTEINS
What the sources say
- Partly supportedcites [60] 60. Mozaffarian D, Wu JH. (n-3) fatty acids and cardiovascular health: are ef- fects of EPA and DHA shared or complementary? J Nutr. 2012;142:614S- 625S. doi: 10.3945/jn.111.149633 sourceExperimental — accuracy not yet measured
The Lipids section (page not supplied) says DHA slightly raised HDL-cholesterol compared with EPA in two trials. It also says effects on other lipid fractions were less consistent and total HDL-cholesterol was not appreciably altered in most trials, so it does not support a consistent increase across studies of people with above-optimal triglycerides. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [61] 61. Grimsgaard S, Bonaa KH, Hansen JB, Nordøy A. Highly purified eicosapen- taenoic acid and docosahexaenoic acid in humans have similar triacylglyc- erol-lowering effects but divergent effects on serum fatty acids. Am J Clin Nutr. 1997;66:649-659. doi: 10.1093/ajcn/66.3.649 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In studies of O3AEE in patients with HTG, 4 g/d (3.4 g/d EPA+DHA) has demonstrated greater efficacy (20%-30% reduction) than the 2-g/d dose (1.7 g/d EPA+DHA), which resulted in modest reductions of 11% to 15% 50,67 or no significant triglyceride reduction.36,68”
§ e673 > DOSING CONSIDERATIONS
What the sources say
- Not checked — no full text of the sourcecites [50] 50. Vecka M, Dušejovská M, Stankova B, Zeman M, Vavrova L, Kodydkova J, Slaby A, Zak A. N-3 polyunsaturated fatty acids in the treatment of ath- erogenic dyslipidemia. Neuro Endocrinol Lett. 2012;33(suppl 2):87-92.
- Not checked — no full text of the sourcecites [67] 67. Balk EM, Adam GP, Langberg V, Halladay C, Chung M, Lin L, Robertson S, Yip A, Steele D, Smith BT. Omega-3 Fatty Acids and Cardiovascular Dis- ease: An Updated Systematic Review. Washington, DC: Agency for Healthcare Research and Quality, US Department of Health and Human Services; 2016. source
- Partly supportedcites [36] 36. Metkus TS, Timpone J, Leaf D, Bidwell Goetz M, Harris WS, Brown TT. Omega-3 fatty acid therapy reduces triglycerides and interleu- kin-6 in hypertriglyeridemic HIV patients. HIV Med. 2013;14:530-539. doi: 10.1111/hiv.12046 sourceExperimental — accuracy not yet measured
The Methods (Treatment; page unavailable) report four 1000-mg omega-3 capsules daily, and the Results (Effect of O3A ethyl esters on lipid parameters; page unavailable) report a statistically significant triglyceride reduction. The median reduction was 9% in the active-treatment group; the Discussion describes it as 24% versus placebo. This study did not test a 2-g/day dose or establish the claimed comparison between doses. (LLM, conf=0.85)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“and in 2 of these investigations, apo B was also reduced by 2% to 3%.22,33”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [22] 22. Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. Eicosapentaenoic acid ethyl ester (AMR101) therapy in pa- tients with very high triglyceride levels (from the Multi-center, plAcebo- controlled, Randomized, double-blINd, 12-week study with an open- label Extension [MARINE] trial). Am J Cardiol. 2011;108:682-690. doi: 10.1016/j.amjcard.2011.04.015 source
- Supportedcites [33] 33. Bays HE, McKenney J, Maki KC, Doyle RT, Carter RN, Stein E. Effects of prescription omega-3-acid ethyl esters on non-high-density lipoprotein cholesterol when coadministered with escalating doses of atorvastatin. Mayo Clin Proc. 2010;85:122-128. doi: 10.4065/mcp.2009.0397 source
The Other Lipid and Lipoprotein Parameters section reports a 3.2-percentage-point greater reduction in apo B with omega-3-acid ethyl esters plus atorvastatin than with atorvastatin alone during the 20-mg phase. That supports the approximately 3% reduction attributed to this study; the copy cannot establish the result of the other cited investigation. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“meta-analyses of older studies and more recent publications have shown that 4 g/d Downloaded from http://ahajournals.org by on September 1, 2023”
- Also stated in: § CLINICAL STATEMENTS AND GUIDELINES · plain
“prescription n-3 FA does not adversely affect glucose metabolism.[98][99][100]”
§ e673 > Glycemic Control
What the sources say
- Not checked — no full text of the sourcecites [98] 98. Mark BJ, Beaty AD, Slavin RG. Are fish oil supplements safe in finned fish-allergic patients? Allergy Asthma Proc. 2008;29:528-529. doi: 10.2500/aap.2008.29.3159 source
- Partly supportedcites [99] 99. Chen C, Yu X, Shao S. Effects of omega-3 fatty acid supplementation on glucose control and lipid levels in type 2 diabetes: a meta-analysis. PLoS One. 2015;10:e0139565. doi: 10.1371/journal.pone.0139565 sourceExperimental — accuracy not yet measured
The Effects of interventions section reports no significant overall change in fasting or postprandial glucose, insulin, or HbA1c with omega-3 supplementation in people with type 2 diabetes. It does not establish that a 4 g/day prescription formulation has no adverse effect: the Description of studies reports varying supplement doses, and the Subgroup analysis and heterogeneity section reports a significant increase in fasting glucose among Asian participants. Page numbers are unavailable in our copy. (LLM, conf=0.88)
- Partly supportedcites [100] 100. Akinkuolie AO, Ngwa JS, Meigs JB, Djoussé L. Omega-3 polyunsaturated fatty acid and insulin sensitivity: a meta-analysis of randomized controlled trials. Clin Nutr. 2011;30:702-707. doi: 10.1016/j.clnu.2011.08.013 100. sourceExperimental — accuracy not yet measured
The Discussion (section 3; page unavailable) says the meta-analysis found no overall association between omega-3 PUFA and insulin sensitivity and suggests it may not perturb glucose–insulin homeostasis. Although the study table includes trials using 4 g/day, the Discussion explicitly says the analysis did not address dose, and the paper does not establish the claim specifically for 4 g/day prescription products. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § CLINICAL STATEMENTS AND GUIDELINES · plain
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Apparently independently of formulation, some omega-3 dietary supplements contain cholesterol, oxidized fatty acids, saturated fatty acids, or other contaminants that can affect their net risk-benefit relationship.57,105”
§ e673 > Writing Group
What the sources say
- Not checked — no full text of the sourcecites [57] 57. Wei MY, Jacobson TA. Effects of eicosapentaenoic acid versus docosa- hexaenoic acid on serum lipids: a systematic review and meta-analysis. Curr Atheroscler Rep. 2011;13:474-483. doi: 10.1007/s11883-011-0210-3 source
- Could not verifycites [105] 105. Nicholls SJ, Lincoff AM, Bash D, Ballantyne CM, Barter PJ, Davidson MH, Kastelein JJP, Koenig W, McGuire DK, Mozaffarian D, Pedersen TR, Ridker PM, Ray K, Karlson BW, Lundström T, Wolski K, Nissen SE. Assess- ment of omega-3 carboxylic acids in statin-treated patients with high lev- els of triglycerides and low levels of high-density lipoprotein cholesterol: rationale and design of the STRENGTH trial. Clin Cardiol. 2018;41:1281- 1288. doi: 10.1002/clc.23055 105. Brinton EA, Mason RP. Prescription omega-3 fatty acid products con- taining highly purified eicosapentaenoic acid (EPA). Lipids sourceExperimental — accuracy not yet measured
Section 4, “Omega-3 Fatty Acids” (page unavailable), discusses variable formulation bioavailability and uncertain cardiovascular benefit, but not the composition or contamination of dietary supplements. Searches for cholesterol, oxidized fatty acids, saturated fatty acids, and contaminants in supplements found no passage addressing the claimed effect on their risk-benefit relationship. (LLM, conf=0.76)
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Prescription doses of n-3 FA appear to be as safe for the management of elevated triglycerides in adolescents and children as young as 10 years of age as they are for adults.78,79”
§ e673 > EFFECTS IN CHILDREN AND ADOLESCENTS WITH ELEVATED TRIGLYCERIDES
What the sources say
- Not checked — no full text of the sourcecites [78] 78. Celik S, Doesch A, Erbel C, Blessing E, Ammon K, Koch A, Katus HA, Dengler TJ. Beneficial effect of omega-3 fatty acids on sirolimus-or everolimus-induced hypertriglyceridemia in heart trans- plant recipients. Transplantation. 2008;86:245-250. doi: 10.1097/TP. 0b013e318177281e source
- Partly supportedcites [79] 79. Gidding SS, Prospero C, Hossain J, Zappalla F, Balagopal PB, Falkner B, Kwiterovich P. A double-blind randomized trial of fish oil to lower tri- glycerides and improve cardiometabolic risk in adolescents. J Pediatr. 2014;165:497-503.e2. doi: 10.1016/j.jpeds.2014.05.039 sourceExperimental — accuracy not yet measured
The Methods section enrolled adolescents eligible from ages 10–17 with elevated triglycerides, and the Results section says 4 g/day fish oil was well tolerated, with medication-related adverse events that were mild to moderate. The paper does not compare safety with adults, and eligibility from age 10 does not establish that a 10-year-old participant received treatment. (LLM, conf=0.85)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Clinical research has further established that doses of <2 g/d EPA+DHA are not effective for reducing triglycerides compared with higher doses, even in people with HTG.33”
§ e673 > DOSING CONSIDERATIONS
What the sources say
- Partly supportedcites [33] 33. Bays HE, McKenney J, Maki KC, Doyle RT, Carter RN, Stein E. Effects of prescription omega-3-acid ethyl esters on non-high-density lipoprotein cholesterol when coadministered with escalating doses of atorvastatin. Mayo Clin Proc. 2010;85:122-128. doi: 10.4065/mcp.2009.0397 sourceExperimental — accuracy not yet measured
The Other Lipid and Lipoprotein Parameters section (page unavailable) reports that 4 g/d prescription omega-3-acid ethyl esters significantly reduced triglycerides in patients with elevated triglycerides. The study compared that dose with placebo, not with doses below 2 g/d, so it does not establish that lower doses are ineffective. (LLM, conf=0.85)
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In extreme cases, dietary n-3 FA supplements may have up to 37% saturated fat content.106”
§ e673 > Writing Group
What the sources say
- Partly supportedcites [106] 106. Mason RP, Sherratt SCR. Omega-3 fatty acid fish oil dietary supple- ments contain saturated fats and oxidized lipids that may interfere with their intended biological benefits. Biochem Biophys Res Commun. 2017;483:425-429. doi: 10.1016/j.bbrc.2016.12.127 107. sourceExperimental — accuracy not yet measured
The Results (section 3; page not provided) report that saturated fats made up as much as 36% of total fatty acid content in three supplements tested. This supports the point that the content can be high, but not the stated maximum of 37%. (LLM, conf=0.88)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“This is consistent with trials reporting no increased risk of bleeding with n-3 FA added to either anticoagulants or antiplatelet drugs.94,95”
§ e673 > Bleeding
What the sources say
- Not checked — no full text of the sourcecites [94] 94. Davidson MH, Johnson J, Rooney MW, Kyle ML, Kling DF. A novel omega-3 free fatty acid formulation has dramatically improved bioavail- ability during a low-fat diet compared with omega-3-acid ethyl esters: the ECLIPSE (Epanova(®) compared to Lovaza(®) in a pharmacokinetic single-dose evaluation) study. J Clin Lipidol. 2012;6:573-584. doi: 10.1016/j.jacl.2012.01.002 source
- Supportedcites [95] 95. Wachira JK, Larson MK, Harris WS. n-3 Fatty acids affect haemo- stasis but do not increase the risk of bleeding: clinical observa- tions and mechanistic insights. Br J Nutr. 2014;111:1652-1662. doi: 10.1017/S000711451300425X source
The Randomised controlled studies section reports no excess bleeding when fish oil was added to aspirin or warfarin. It also reports no increased bleeding in a trial adding n-3 fatty acids to dual antiplatelet therapy. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Inhibition of diacyl-glycerol acyl transferase, the major triglyceride-synthesizing enzyme in the liver, has also been reported with n-3 FA use.83”
§ e673 > MECHANISMS OF N-3 FA EFFECTS ON LIPOPROTEIN METABOLISM
What the sources say
- Supportedcites [83] 83. Shearer GC, Savinova OV, Harris WS. Fish oil: how does it reduce plas- ma triglycerides? Biochim Biophys Acta. 2012;1821:843-851. doi: 10.1016/j.bbalip.2011.10.011 source
Section 8.1, “Liver,” reports that EPA-CoA inhibits diacylglycerol acyltransferase activity and thereby reduces triglyceride synthesis in rat liver microsomes. This supports the citing sentence’s reported mechanism; the paper specifies that the cited enzyme finding was in rat liver microsomes. (LLM, conf=0.90)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“the few studies of n-3 FA supplementation in children/ adolescents with HTG have not shown a significant triglyceride-lowering effect.78,79,81”
§ e673 > EFFECTS IN CHILDREN AND ADOLESCENTS WITH ELEVATED TRIGLYCERIDES
What the sources say
- Not checked — no full text of the sourcecites [78] 78. Celik S, Doesch A, Erbel C, Blessing E, Ammon K, Koch A, Katus HA, Dengler TJ. Beneficial effect of omega-3 fatty acids on sirolimus-or everolimus-induced hypertriglyceridemia in heart trans- plant recipients. Transplantation. 2008;86:245-250. doi: 10.1097/TP. 0b013e318177281e source
- Supportedcites [79] 79. Gidding SS, Prospero C, Hossain J, Zappalla F, Balagopal PB, Falkner B, Kwiterovich P. A double-blind randomized trial of fish oil to lower tri- glycerides and improve cardiometabolic risk in adolescents. J Pediatr. 2014;165:497-503.e2. doi: 10.1016/j.jpeds.2014.05.039 source
The Abstract Results report that triglycerides fell in adolescents receiving fish oil, but the reduction was not statistically significant compared with placebo. This supports the claim as it applies to this cited trial; the other studies in the citing sentence are covered by separate citations. (LLM, conf=0.92)
- Not matchedcites [81] 81. Lovaza (omega-3-acid ethyl esters) [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2009.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Thus, use of the Friedewald estimation for LDL-C becomes increasingly problematic as triglyceride concentrations increase in the 100-to 400-mg/dL range.115”
§ e673 > Writing Group
What the sources say
- Supportedcites [115] 115. Martin SS, Blaha MJ, Elshazly MB, Toth PP, Kwiterovich PO, Blumenthal RS, Jones SR. Comparison of a novel method vs the Frie- dewald equation for estimating low-density lipoprotein cholesterol lev- els from the standard lipid profile. JAMA. 2013;310:2061-2068. doi: 10.1001/jama.2013.280532 source
The Results show that, among samples with estimated LDL-C below 70 mg/dL, Friedewald classification concordance fell as triglycerides rose: 79.9% at 100–149 mg/dL, 61.3% at 150–199 mg/dL, and 40.3% at 200–399 mg/dL. The Discussion likewise identifies higher triglyceride concentrations as a setting in which estimation errors become more important, particularly at lower LDL-C levels. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Only 3 of the trials presented in Table 4 specified that results were based on 2 independent measurements separated by at least 1 day.32,33,39”
§ e673 > Writing Group
What the sources say
- Not checked — no full text of the sourcecites [32] 32. Davidson MH, Stein EA, Bays HE, Maki KC, Doyle RT, Shalwitz RA, Ballantyne CM, Ginsberg HN; COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double- blind, placebo-controlled study. Clin Ther. 2007;29:1354-1367. doi: 10.1016/j.clinthera.2007.07.018 source
- Supportedcites [33] 33. Bays HE, McKenney J, Maki KC, Doyle RT, Carter RN, Stein E. Effects of prescription omega-3-acid ethyl esters on non-high-density lipoprotein cholesterol when coadministered with escalating doses of atorvastatin. Mayo Clin Proc. 2010;85:122-128. doi: 10.4065/mcp.2009.0397 source
The End Points passage (page unavailable) says the trial calculated its baseline from two fasting measurements and its treatment-period results from measurements at separate weekly visits. This supports citing the trial as one that used two measurements separated by at least a day; this paper does not establish the citing document’s count of three trials. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [39] 39. Hedengran A, Szecsi PB, Dyerberg J, Harris WS, Stender S. n-3 PUFA es- terified to glycerol or as ethyl esters reduce non-fasting plasma triacylg- lycerol in subjects with hypertriglyceridemia: a randomized trial. Lipids. 2015;50:165-175. doi: 10.1007/s11745-014-3968-6 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“As reviewed in the 2011 AHA statement on triglycerides and cardiovascular disease, 1 alcohol consumption just before testing may elevate fasting triglyceride measurements.118,119”
§ e673 > Writing Group
What the sources say
- Partly supportedcites [1] 1. Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, Kris-Etherton PM, Lennie TA, Levi M, Mazzone T, Pennathur S; on behalf of the American Heart As- sociation Clinical Lipidology, Thrombosis, and Prevention Committee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Car- diovascular Nursing; Council on the Kidney in Cardiovascular Disease. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. sourceExperimental — accuracy not yet measured
Section 13.5 (Alcohol; page unavailable) reports that higher alcohol intake raises triglyceride levels. Sections 10 and 10.3 discuss factors affecting triglyceride measurements and fasting versus nonfasting tests, but do not establish that alcohol consumed just before testing elevates a fasting measurement. (LLM, conf=0.84)
- Could not verifycites [118] 118. Havel RJ. Early effects of fat ingestion on lipids and lipoproteins of serum in man. J Clin Invest. 1957;36(pt 1):848-854. doi: 10.1172/JCI103491 119. 113. Patsch JR, Karlin JB, Scott LW, Smith LC, Gotto AM. Inverse relationship between blood levels of high density lipoprotein subfraction 2 and mag- nitude of postprandial lipemia. Proc Natl Acad Sci U S A. 1983;80:1449- 1453. doi: 10.1073/pnas.80.5.1449 120. 114. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting com- pared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007;298:309-316. do sourceExperimental — accuracy not yet measured
The Methods describe fasting before a high-fat breakfast and using ethanol as a laboratory extraction solvent; the Serum lipids and Discussion sections report triglyceride changes after fat ingestion. Searches for alcohol consumption and fasting triglyceride measurements found no passage addressing whether drinking before testing elevates the measurement. The passages provided do not give page numbers. (LLM, conf=0.76)
- Not checked — no full text of the sourcecites [119] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When expressed as a percent change from baseline, there was no LDL-C effect of O3AEE, IPE, or O3CA in patients with HTG in these trials.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Head-to-head comparisons of EPA alone and EPA+DHA agents at FDA-approved doses are not available.”
§ e673 > COMPARISON OF EPA+DHA VERSUS EPA-ONLY AGENTS ON LIPIDS AND LIPOPROTEINS IN INDIVIDUALS WITH HTG
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Overall, these results demonstrate that in patients with HTG, the combination of n-3 FA with fenofibrate or niacin can result in additive triglyceride reductions, but more research is needed.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Indeed, effects on LDL-C were nonsignificant or marginally significant (1 study, P=0.052) in studies of 4 g/d O3AEE in which triglyceride reductions were ≤30%.26,28,[30][31][32][33]36,37”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [26] 26. Maki KC, Bays HE, Dicklin MR, Johnson SL, Shabbout M. Effects of prescription omega-3-acid ethyl esters, coadministered with atorv- astatin, on circulating levels of lipoprotein particles, apolipoprotein CIII, and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia. J Clin Lipidol. 2011;5:483-492. doi: 10.1016/j.jacl.2011.09.001 source
- Not checked — no full text of the sourcecites [28] 28. Roth EM, Bays HE, Forker AD, Maki KC, Carter R, Doyle RT, Stein EA. Prescription omega-3 fatty acid as an adjunct to fenofibrate therapy in hypertriglyceridemic subjects. J Cardiovasc Pharmacol. 2009;54:196-203. doi: 10.1097/FJC.0b013e3181b0cf71 source
- Not checked — no full text of the sourcecites [30] 30. Grundt H, Nilsen DW, Hetland O, Aarsland T, Baksaas I, Grande T, Woie L. Improvement of serum lipids and blood pressure during intervention with n-3 fatty acids was not associated with changes in insulin levels in subjects with combined hyperlipidaemia. J Intern Med. 1995;237:249-259. doi: 10.111/j.1365-2796.1995.tb01173.x source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“An earlier open-label study of 2 g/d IPE found that triglycerides decreased only 5%.69”
§ e673 > DOSING CONSIDERATIONS
What the sources say
- Not checked — no full text of the sourcecites [69] 69. Koh KK, Quon MJ, Shin KC, Lim S, Lee Y, Sakuma I, Lee K, Han SH, Shin EK. Significant differential effects of omega-3 fatty acids and fenofibrate in patients with hypertriglyceridemia. Atherosclerosis. 2012;220:537-544. doi: 10.1016/j.atherosclerosis.2011.11.018 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“For instance, 4 g/d IPE (≈3.8 g/d EPA) resulted in a 22% decrease versus 10% with 2 g/d IPE (≈1.9 g/d EPA).39”
§ e673 > DOSING CONSIDERATIONS
What the sources say
- Not checked — no full text of the sourcecites [39] 39. Hedengran A, Szecsi PB, Dyerberg J, Harris WS, Stender S. n-3 PUFA es- terified to glycerol or as ethyl esters reduce non-fasting plasma triacylg- lycerol in subjects with hypertriglyceridemia: a randomized trial. Lipids. 2015;50:165-175. doi: 10.1007/s11745-014-3968-6 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“whereas in 1 study, the median LDL-C was marginally increased by 3.5% versus placebo (P=0.052).31”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [31] 31. Durrington PN, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, France M. An omega-3 polyunsaturated fatty acid concentrate adminis- tered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001;85:544-548. doi: 10.1136/heart.85.5.544 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“A similar finding for LDL-C was reported from REDUCE-IT, in which the effect of IPE was -6.6% (control, 10.2%; active, 3.1%).40”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [40] 40. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, Soni PN. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110:984-92. doi: 10.1016/j.amjcard.2012.05.031 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“but head-to-head comparisons of EPAonly versus DHA-only agents are not available in patients with HTG or VHTG.”
§ e673 > EFFECTS OF EPA-ONLY VERSUS DHA-ONLY ON LIPIDS AND LIPOPROTEINS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In 8 of these 9 studies, there Circulation.2019;140:e673-e691.DOI: 10.1161/CIR.0000000000000709September 17, 2019 e681”
- Also stated in: § CLINICAL STATEMENTS AND GUIDELINES · plain
“was no change in LDL-C versus placebo (4 of which used n-3 FA as an adjunct to statin therapy)”
§ e673 > COMPARISON OF EPA+DHA VERSUS EPA-ONLY AGENTS ON LIPIDS AND LIPOPROTEINS IN INDIVIDUALS WITH HTG
What the sources say
- Not checked — no full text of the sourcecites [31] 31. Durrington PN, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, France M. An omega-3 polyunsaturated fatty acid concentrate adminis- tered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001;85:544-548. doi: 10.1136/heart.85.5.544 source
plainn = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § CLINICAL STATEMENTS AND GUIDELINES · plain
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In summary, all 3 prescription agents were effective for reducing triglycerides and atherogenic lipoproteins when combined with statin therapy.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Eight trials evaluated 4 g/d prescription n-3 FA in people with HTG on background statin therapy.”
§ e673 > n-3 FA Added to Other Lipid-Lowering Therapies
What the sources say
- Not checked — no full text of the sourcecites [26] 26. Maki KC, Bays HE, Dicklin MR, Johnson SL, Shabbout M. Effects of prescription omega-3-acid ethyl esters, coadministered with atorv- astatin, on circulating levels of lipoprotein particles, apolipoprotein CIII, and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia. J Clin Lipidol. 2011;5:483-492. doi: 10.1016/j.jacl.2011.09.001 source
- Not checked — no full text of the sourcecites [30] 30. Grundt H, Nilsen DW, Hetland O, Aarsland T, Baksaas I, Grande T, Woie L. Improvement of serum lipids and blood pressure during intervention with n-3 fatty acids was not associated with changes in insulin levels in subjects with combined hyperlipidaemia. J Intern Med. 1995;237:249-259. doi: 10.111/j.1365-2796.1995.tb01173.x source
- Not checked — no full text of the sourcecites [31] 31. Durrington PN, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, France M. An omega-3 polyunsaturated fatty acid concentrate adminis- tered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001;85:544-548. doi: 10.1136/heart.85.5.544 source
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Effects on apo B did not differ between EPA and DHA.”
§ e673 > EFFECTS OF EPA-ONLY VERSUS DHA-ONLY ON LIPIDS AND LIPOPROTEINS
What the sources say
- Not checked — no full text of the sourcecites [61] 61. Grimsgaard S, Bonaa KH, Hansen JB, Nordøy A. Highly purified eicosapen- taenoic acid and docosahexaenoic acid in humans have similar triacylglyc- erol-lowering effects but divergent effects on serum fatty acids. Am J Clin Nutr. 1997;66:649-659. doi: 10.1093/ajcn/66.3.649 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, doses >4 g/d have not been systematically studied for any of the n-3 FA agents.”
§ e673 > DOSING CONSIDERATIONS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Furthermore, EPA reduces de novo lipogenesis by inhibiting transcription of the gene for SREBP (sterol regulatory element binding protein)-1c.85”
§ e673 > MECHANISMS OF N-3 FA EFFECTS ON LIPOPROTEIN METABOLISM
What the sources say
- Not checked — no full text of the sourcecites [85] 85. Miller M, Motevalli M, Westphal D, Kwiterovich PO Jr. Incorporation of oleic acid and eicosapentaenoic acid into glycerolipids of cultured normal human fibroblasts. Lipids. 1993;28:1-5. doi: 10.1007/BF02536351 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“n-3 FAs have uniformly been reported to lower triglycerides when used with interferon-α, 70 antipsychotics, 71,72 l-asparaginase, 73 oral estrogens, 74 protease inhibitors, 35,75 retinoic acid, 76 and sirolimus.77”
§ e673 > TREATMENT OF MEDICATION-INDUCED HTG WITH N-3 FAs
What the sources say
- Not checked — no full text of the sourcecites [70] 70. Saito Y, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; JELIS Investi- gators, Japan. Effects of EPA on coronary artery disease in hypercho- lesterolemic patients with multiple risk factors: sub-analysis of pri- mary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis. 2008;200:135-140. doi: 10.1016/j.atherosclerosis. 2008.06.003 source
- Not checked — no full text of the sourcecites [71] 71. Malaguarnera M, Restuccia N, Fazio ID, Panebianco MP, Gulizia G, Giugno I. Fish oil treatment of interferon-alpha-induced dyslipidaemia: study in patients with chronic hepatitis C. BioDrugs. 1999;11:285-291. doi: 10.2165/00063030-199911040-00007 source
- Not checked — no full text of the sourcecites [72] 72. Freeman MP, McInerney K, Sosinsky AZ, Kwiatkowski MA, Cohen LS. Omega-3 fatty acids for atypical antipsychotic-associated hypertriglyceri- demia. Ann Clin Psychiatry. 2015;27:197-202. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“However, the subset of patients (≈20% of the total cohort) who began the trial with triglycerides >200 mg/dL and HDL-C ≤35 mg/dL experienced a significantly greater risk reduction of the primary end point than those not meeting these criteria: 38% (95% CI, 23-49) versus 21% (95% CI, 12-29), respectively (P=0.04 for interaction).”
§ e673 > CARDIOVASCULAR OUTCOME TRIALS OF N-3 FA IN STATIN-TREATED INDIVIDUALS WITH HTG
What the sources say
- Not checked — no full text of the sourcecites [40] 40. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, Soni PN. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110:984-92. doi: 10.1016/j.amjcard.2012.05.031 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“At this dose, triglyceride lowering of ≥30% has been reported in clinical trials of subjects with VHTG (triglycerides ≥500 mg/dL), in whom these agents are FDA approved.”
§ e673 > SUMMARY AND CONCLUSIONS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Cardiovascular disease risk reduction did not differ between patients, with on-study triglycerides >150 or <150 mg/dL at 1 year.”
§ e673 > CARDIOVASCULAR OUTCOME TRIALS OF N-3 FA IN STATIN-TREATED INDIVIDUALS WITH HTG
What the sources say
- Not checked — no full text of the sourcecites [40] 40. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, Soni PN. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110:984-92. doi: 10.1016/j.amjcard.2012.05.031 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Kinetic studies have demonstrated that n-3 FAs reduce hepatic secretion of triglyceride-rich lipoproteins, the molecular mechanisms of which have not been fully characterized.82”
§ e673 > MECHANISMS OF N-3 FA EFFECTS ON LIPOPROTEIN METABOLISM
What the sources say
- Not checked — no full text of the sourcecites [82] 82. Engler MM, Engler MB, Malloy MJ, Paul SM, Kulkarni KR, Mietus-Snyder ML. Effect of docosahexaenoic acid on lipoprotein subclasses in hyperlipid- emic children (the EARLY study). Am J Cardiol. 2005;95:869-871. doi: 10.1016/j.amjcard.2004.12.014 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“a 25% reduction in major adverse cardiovascular end points in REDUCE-IT, a randomized placebo-controlled trial of EPA-only in high-risk patients on statin therapy.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not matchedcites REDUCE-IT
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In clinical trials completed to date, <5% of subjects have discontinued omega-3 agents because of side effects.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Subjects randomized to IPE had a 25% reduction in the primary end point, which was a 5-point composite of major adverse cardiovascular end points consisting of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, and unstable angina requiring hospitalization.40”
§ e673 > CARDIOVASCULAR OUTCOME TRIALS OF N-3 FA IN STATIN-TREATED INDIVIDUALS WITH HTG
What the sources say
- Not checked — no full text of the sourcecites [40] 40. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, Soni PN. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110:984-92. doi: 10.1016/j.amjcard.2012.05.031 source
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In the paper
“Nevertheless, there was no difference between those with and those without these criteria for the secondary composite end point consisting of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (P=0.5).”
§ e673 > CARDIOVASCULAR OUTCOME TRIALS OF N-3 FA IN STATIN-TREATED INDIVIDUALS WITH HTG
What the sources say
- Not checked — no full text of the sourcecites [40] 40. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, Soni PN. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110:984-92. doi: 10.1016/j.amjcard.2012.05.031 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“With regard to the clinical trials evaluated for this advisory, results were most commonly based on a single fasting triglyceride measurement.”
§ e673 > Writing Group
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Plasma triglyceride levels were reduced by 30% to 35% in individuals with baseline triglycerides of 600 to 800 mg/dL.”
§ e673 > EFFECTS OF PRESCRIPTION N-3 FA AT FDA-APPROVED DOSES IN INDIVIDUALS WITH VHTG (≥500 MG/DL)
What the sources say
- Not checked — no full text of the sourcecites [19] 19. Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety consid- erations with fibrate therapy. Am J Cardiol. 2007;99:3C-18C. doi: 10.1016/j.amjcard.2006.11.016 source
- Not checked — no full text of the sourcecites [20] 20. Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, Berglund L, Osmundsen K. Safety and efficacy of Omacor in severe hyper- triglyceridemia. J Cardiovasc Risk. 1997;4:385-391. source
- Not checked — no full text of the sourcecites [21] 21. Pownall HJ, Brauchi D, Kilinç C, Osmundsen K, Pao Q, Payton-Ross C, Gotto AM Jr, Ballantyne CM. Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipopro- teins. Atherosclerosis. 1999;143:285-297. doi: https://doi.org/10.1016/ S0021-9150(98)00301-3 source
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In the paper
“Limited evidence is available from randomized controlled trials on the effects of n-3 FA in combination with nonstatin therapy for the treatment of VHTG.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In patients with VHTG treated with prescription EPA+DHA products, LDL-C increased by ≈15% to 36% † (similar to fenofibrate; Table 3).”
§ e673 > EFFECTS OF PRESCRIPTION N-3 FA AT FDA-APPROVED DOSES IN INDIVIDUALS WITH VHTG (≥500 MG/DL)
What the sources say
- Not checked — no full text of the sourcecites [19] 19. Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety consid- erations with fibrate therapy. Am J Cardiol. 2007;99:3C-18C. doi: 10.1016/j.amjcard.2006.11.016 source
- Not checked — no full text of the sourcecites [20] 20. Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, Berglund L, Osmundsen K. Safety and efficacy of Omacor in severe hyper- triglyceridemia. J Cardiovasc Risk. 1997;4:385-391. source
- Not checked — no full text of the sourcecites [22] 22. Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. Eicosapentaenoic acid ethyl ester (AMR101) therapy in pa- tients with very high triglyceride levels (from the Multi-center, plAcebo- controlled, Randomized, double-blINd, 12-week study with an open- label Extension [MARINE] trial). Am J Cardiol. 2011;108:682-690. doi: 10.1016/j.amjcard.2011.04.015 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In treatment of very high triglycerides with 4 g/d, EPA+DHA agents reduce triglycerides by ≥30% with concurrent increases in low-density lipoprotein cholesterol, whereas EPA-only did not raise low-density lipoprotein cholesterol in very high triglycerides.”
§ e673 > Abstract
What the sources say
- Not checked — no full text of the sourcecites [19] 19. Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety consid- erations with fibrate therapy. Am J Cardiol. 2007;99:3C-18C. doi: 10.1016/j.amjcard.2006.11.016 source
- Not checked — no full text of the sourcecites [20] 20. Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, Berglund L, Osmundsen K. Safety and efficacy of Omacor in severe hyper- triglyceridemia. J Cardiovasc Risk. 1997;4:385-391. source
- Not checked — no full text of the sourcecites [22] 22. Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. Eicosapentaenoic acid ethyl ester (AMR101) therapy in pa- tients with very high triglyceride levels (from the Multi-center, plAcebo- controlled, Randomized, double-blINd, 12-week study with an open- label Extension [MARINE] trial). Am J Cardiol. 2011;108:682-690. doi: 10.1016/j.amjcard.2011.04.015 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In patients with VHTG (triglycerides, 500-2000 mg/dL), treatment with IPE did not raise LDL-C, and apo B decreased, suggesting differing effects from those of EPA+DHA.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“All 3 FDA-approved agents, O3AEE, 19,20 IPE, 21 and O3CA, 22 have been tested at 4 g/d in affected patients.”
§ e673 > EFFECTS OF PRESCRIPTION N-3 FA AT FDA-APPROVED DOSES IN INDIVIDUALS WITH VHTG (≥500 MG/DL)
What the sources say
- Not checked — no full text of the sourcecites [19] 19. Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety consid- erations with fibrate therapy. Am J Cardiol. 2007;99:3C-18C. doi: 10.1016/j.amjcard.2006.11.016 source
- Not checked — no full text of the sourcecites [20] 20. Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, Berglund L, Osmundsen K. Safety and efficacy of Omacor in severe hyper- triglyceridemia. J Cardiovasc Risk. 1997;4:385-391. source
- Not checked — no full text of the sourcecites [21] 21. Pownall HJ, Brauchi D, Kilinç C, Osmundsen K, Pao Q, Payton-Ross C, Gotto AM Jr, Ballantyne CM. Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipopro- teins. Atherosclerosis. 1999;143:285-297. doi: https://doi.org/10.1016/ S0021-9150(98)00301-3 source
plain- Asserted: passes — The authors put it forward as true.
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“With regard to high-density lipoprotein cholesterol (HDL-C), 2 studies from the 1990s using O3AEE 19,20 reported net increases of ≈12%.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [19] 19. Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety consid- erations with fibrate therapy. Am J Cardiol. 2007;99:3C-18C. doi: 10.1016/j.amjcard.2006.11.016 source
- Not checked — no full text of the sourcecites [20] 20. Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, Berglund L, Osmundsen K. Safety and efficacy of Omacor in severe hyper- triglyceridemia. J Cardiovasc Risk. 1997;4:385-391. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“In treatment of very high triglycerides with 4 g/d, EPA+DHA agents reduce triglycerides by ≥30% with concurrent increases in low-density lipoprotein cholesterol, whereas EPA-only did not raise low-density lipoprotein cholesterol in very high triglycerides.”
§ e673 > Abstract
What the sources say
- Not checked — no full text of the sourcecites [21] 21. Pownall HJ, Brauchi D, Kilinç C, Osmundsen K, Pao Q, Payton-Ross C, Gotto AM Jr, Ballantyne CM. Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipopro- teins. Atherosclerosis. 1999;143:285-297. doi: https://doi.org/10.1016/ S0021-9150(98)00301-3 source
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When used to treat hypertriglyceridemia, n-3 FAs with EPA+DHA or with EPA-only appear roughly comparable for triglyceride lowering and do not increase low-density lipoprotein”
§ e673 > Abstract
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“In the only study examining effects in patients with overall mean triglycerides of ≈900 mg/dL, a placebo-adjusted triglyceride reduction of 60% was observed.”
§ e673 > EFFECTS OF PRESCRIPTION N-3 FA AT FDA-APPROVED DOSES IN INDIVIDUALS WITH VHTG (≥500 MG/DL)
What the sources say
- Not checked — no full text of the sourcecites [19] 19. Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety consid- erations with fibrate therapy. Am J Cardiol. 2007;99:3C-18C. doi: 10.1016/j.amjcard.2006.11.016 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In a subanalysis of the IPE study, the placebo-corrected triglyceride-lowering effect in patients with triglycerides >750 mg/dL (mean, ≈900 mg/dL) was 45% (control, 19%; active, -27%).”
§ e673 > EFFECTS OF PRESCRIPTION N-3 FA AT FDA-APPROVED DOSES IN INDIVIDUALS WITH VHTG (≥500 MG/DL)
What the sources say
- Not checked — no full text of the sourcecites [21] 21. Pownall HJ, Brauchi D, Kilinç C, Osmundsen K, Pao Q, Payton-Ross C, Gotto AM Jr, Ballantyne CM. Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipopro- teins. Atherosclerosis. 1999;143:285-297. doi: https://doi.org/10.1016/ S0021-9150(98)00301-3 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the largest trials of 4 g/d prescription n-3 FA, non-high-density lipoprotein cholesterol and apolipoprotein B were modestly decreased, indicating reductions in total atherogenic lipoproteins.”
§ e673 > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, there was no increase in apo B (apolipoprotein B) in the 1 study in which it was reported, 22 suggesting that the increase in LDL-C may reflect an increase in the average size of the LDL particles rather than an increase in LDL particle concentration.”
§ e673 > EFFECTS OF PRESCRIPTION N-3 FA AT FDA-APPROVED DOSES IN INDIVIDUALS WITH VHTG (≥500 MG/DL)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Risk of acute pancreatitis is increased in patients with VHTG, especially those with triglycerides ≥1000 mg/dL.”
§ e673 > E
What the sources say
- Not checked — no full text of the sourcecites [9] 9. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cho- lesterol in Adults. Executive summary of the Third Report of The Na- tional Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497. doi: 10.1001/jama. 285.19.2486 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The use of n-3 FA (4 g/d) for improving atherosclerotic cardiovascular disease risk in patients with hypertriglyceridemia is supported by a 25% reduction in major adverse cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With EPA Intervention Trial), a randomized placebo-controlled trial of EPA-only in high-risk patients treated with a statin.”
§ e673 > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The REDUCE-IT result with EPA-only can support the use of n-3 fatty acids generally for improving atherosclerotic cardiovascular disease risk in patients with hypertriglyceridemia.
In the paper
“However, there was no increase in apo B (apolipoprotein B) in the 1 study in which it was reported, 22 suggesting that the increase in LDL-C may reflect an increase in the average size of the LDL particles rather than an increase in LDL particle concentration.”
§ e673 > EFFECTS OF PRESCRIPTION N-3 FA AT FDA-APPROVED DOSES IN INDIVIDUALS WITH VHTG (≥500 MG/DL)
What the sources say
- Not checked — no full text of the sourcecites [22] 22. Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. Eicosapentaenoic acid ethyl ester (AMR101) therapy in pa- tients with very high triglyceride levels (from the Multi-center, plAcebo- controlled, Randomized, double-blINd, 12-week study with an open- label Extension [MARINE] trial). Am J Cardiol. 2011;108:682-690. doi: 10.1016/j.amjcard.2011.04.015 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“The use of n-3 FA (4 g/d) for improving atherosclerotic cardiovascular disease risk in patients with hypertriglyceridemia is supported by a 25% reduction in major adverse cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With EPA Intervention Trial), a randomized placebo-controlled trial of EPA-only in high-risk patients treated with a statin.”
§ e673 > Abstract
What the sources say
- Not matchedcites Bhatt et al., 40
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In the largest trials of 4 g/d prescription n-3 FA, non-high-density lipoprotein cholesterol and apolipoprotein B were modestly decreased, indicating reductions in total atherogenic lipoproteins.”
§ e673 > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In treatment of very high triglycerides with 4 g/d, EPA+DHA agents reduce triglycerides by ≥30% with concurrent increases in low-density lipoprotein cholesterol, whereas EPA-only did not raise low-density lipoprotein cholesterol in very high triglycerides.”
§ e673 > Abstract
What the sources say
- Not checked — no full text of the sourcecites [19] 19. Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety consid- erations with fibrate therapy. Am J Cardiol. 2007;99:3C-18C. doi: 10.1016/j.amjcard.2006.11.016 source
- Not checked — no full text of the sourcecites [20] 20. Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, Berglund L, Osmundsen K. Safety and efficacy of Omacor in severe hyper- triglyceridemia. J Cardiovasc Risk. 1997;4:385-391. source
- Not checked — no full text of the sourcecites [22] 22. Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. Eicosapentaenoic acid ethyl ester (AMR101) therapy in pa- tients with very high triglyceride levels (from the Multi-center, plAcebo- controlled, Randomized, double-blINd, 12-week study with an open- label Extension [MARINE] trial). Am J Cardiol. 2011;108:682-690. doi: 10.1016/j.amjcard.2011.04.015 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Changes in other lipoprotein classes are also important considerations for evaluating the effects of n-3 FA products; however, it should be noted that measurement of low-density lipoprotein (LDL) cholesterol (LDL-C) in the context of elevated triglycerides may not be accurate, as discussed further in the Appendix.”
§ e673 > EFFECTS OF PRESCRIPTION N-3 FA AT FDA-APPROVED DOSES IN INDIVIDUALS WITH VHTG (≥500 MG/DL)
What the sources say
- Not matchedcites Appendix
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, modest reductions in the atherogenic lipoproteins non-HDL-C or apo B are likely with n-3 FA treatment in this population.”
- Also stated in: § CLINICAL STATEMENTS AND GUIDELINES · plain
“Modest reductions in non-HDL-C (5%-14%) and apo B (2%-9%) have been reported with n-3 FA therapy in HTG, which may reflect improved atherogenic risk.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
plainconditional- Asserted: passes — The authors put it forward as true.
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- Also stated in: § CLINICAL STATEMENTS AND GUIDELINES · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The lack of studies directly comparing the 3 prescription n-3 FA agents limits firm conclusions about the comparative effects of these agents on triglycerides and other lipid measures.”
- Also stated in: § CLINICAL STATEMENTS AND GUIDELINES · plain
“The dearth of studies directly comparing the 3 prescription n-3 FA agents precludes any firm conclusions on the comparative effects of these agents on triglycerides, as well as other lipids and lipoproteins.”
§ e673 > COMPARISON OF EPA+DHA VERSUS EPA-ONLY AGENTS ON LIPIDS AND LIPOPROTEINS IN INDIVIDUALS WITH HTG
plain- Asserted: passes — The authors put it forward as true.
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- Also stated in: § CLINICAL STATEMENTS AND GUIDELINES · plain
None of the sources cited for this claim have been checked yet.
In the paper
“The triglyceride decrease was ≈21% (range, 15%-25%).”
§ e673 > n-3 FA Added to Other Lipid-Lowering Therapies
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“An earlier study of a dietary supplement that used a higher dose (4.5 g/d EPA+DHA) reported a 39% reduction in triglycerides after 6 months.”
§ e673 > n-3 FA as Monotherapy
What the sources say
- Not checked — no full text of the sourcecites [42] 42. Maki KC, Orloff DG, Nicholls SJ, Dunbar RL, Roth EM, Curcio D, Johnson J, Kling D, Davidson MH. A highly bioavailable omega-3 free fatty acid formulation improves the cardiovascular risk profile in high-risk, statin-treated patients with residual hypertriglyceridemia (the ESPRIT trial). Clin Ther. 2013;35:1400-11.e1. doi: 10.1016/j.clinthera. 2013.07.420
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, prescription n-3 FAs (regardless of whether they contain DHA) have slight or no effect on LDL-C in patients with HTG.”
- Also stated in: § SUMMARY OF LIPID EFFECTS FOR N-3 FA AT FDA-APPROVED PRESCRIPTION DOSES · plain
“Increased LDL-C with prescription n-3 FA treatment is uncommon in individuals with HTG, regardless of the agent used.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
plain- Asserted: passes — The authors put it forward as true.
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- Also stated in: § SUMMARY OF LIPID EFFECTS FOR N-3 FA AT FDA-APPROVED PRESCRIPTION DOSES · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For individuals with HTG, the effects of EPA-only products on LDL-C relative to DHA-containing products are unclear.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In conclusion, there is no strong evidence that DHA-containing prescription n-3 FA agents used as monotherapy or in combination with statins raise LDL-C in patients with HTG.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
hedged- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This result is consistent with the observation that reductions in triglycerides and increases in HDL-C induced by n-3 FA can correspond to increased LDL-C values resulting from increased LDL particle size.”
§ e673 > EFFECTS OF EPA-ONLY VERSUS DHA-ONLY ON LIPIDS AND LIPOPROTEINS
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This result supports the concept that triglyceride reduction achieved by n-3 FA is not affected by concurrent statin use.”
- Also stated in: § SUMMARY OF LIPID EFFECTS FOR N-3 FA AT FDA-APPROVED PRESCRIPTION DOSES · hedged
“Statin treatment does not appear to influence the degree of triglyceride reduction with n-3 FA administration in patients with HTG (≈20%-30% triglyceride reduction), although this has not been thoroughly evaluated.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § SUMMARY OF LIPID EFFECTS FOR N-3 FA AT FDA-APPROVED PRESCRIPTION DOSES · hedged
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We conclude that prescription n-3 FAs, whether EPA+DHA or EPA-only, at a dose of 4 g/d, are clinically useful for reducing triglycerides, after any underlying causes are addressed and diet and lifestyle strategies are implemented, either as monotherapy or as an adjunct to other triglyceride-lowering therapies (Table 5).”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the reduction in ASCVD risk may be independent of achieving a specific target for fasting triglycerides.”
§ e673 > CARDIOVASCULAR OUTCOME TRIALS OF N-3 FA IN STATIN-TREATED INDIVIDUALS WITH HTG
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Regardless of the type of agent, 4 g/d prescription n-3 FA agents (providing >3 g/d EPA+DHA) have consistently reduced triglyceride levels in patients with elevated triglycerides.”
§ e673 > DOSING CONSIDERATIONS
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hence, n-3 FAs appear to be effective for lowering triglycerides in patients with drug-induced HTG.”
§ e673 > TREATMENT OF MEDICATION-INDUCED HTG WITH N-3 FAs
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Prescription n-3 FAs at the FDA-approved dose of 4 g/d are safe and generally well tolerated.”
§ e673 > SUMMARY AND CONCLUSIONS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results suggest that HTG (particularly in combination with low HDL-C) could be a useful biomarker for identifying patients who may experience the greatest benefit from prescription n-3 FA.”
§ e673 > CARDIOVASCULAR OUTCOME TRIALS OF N-3 FA IN STATIN-TREATED INDIVIDUALS WITH HTG
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The use of n-3 FAs (4 g/d) for improving ASCVD risk in patients with HTG is supported by a 25% reduction in major adverse cardiovascular end points in REDUCE-IT, a randomized placebo-controlled trial of EPA-only in high-risk patients on statin therapy.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not matchedcites REDUCE-IT
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The error introduced by either the use of the Friedewald equation or direct measurements of LDL-C may confound the interpretation of clinical trial results.”
§ e673 > Writing Group
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Plasma lipid concentrations, particularly triglycerides, fluctuate day to day within individuals in response to diet, alcohol, physical activity, and other factors.113”
§ e673 > Writing Group
What the sources say
- Not checked — no full text of the sourcecites [113] 113. Warnick GR, Wood PD. National Cholesterol Education Program rec- ommendations for measurement of high-density lipoprotein choles- terol: executive summary: the National Cholesterol Education Program Working Group on Lipoprotein Measurement. Clin Chem. 1995;41: 1427-1433. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Furthermore, the EPA+DHA content of dietary supplements is not always confirmed by independent analysis.112”
§ e673 > Writing Group
What the sources say
- Not checked — no full text of the sourcecites [112] 112. Kleiner AC, Cladis DP, Santerre CR. A comparison of actual versus stated label amounts of EPA and DHA in commercial omega-3 dietary supple- ments in the United States. J Sci Food Agric. 2015;95:1260-1267. doi: 10.1002/jsfa.6816 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, as a result of inevitable decreases in average LDL particle size with increasing plasma triglycerides, even an accurately determined LDL-C level will tend to progressively underestimate the concentration of LDL particles for triglycerides levels in the 100-to 400-mg/dL range.”
§ e673 > Writing Group
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Unfortunately, homogeneous assays of LDL-C (so-called direct measurements of LDL-C) also lose accuracy in patients with HTG and in nonfasting samples.116”
§ e673 > Writing Group
What the sources say
- Not checked — no full text of the sourcecites [116] 116. Miller WG, Waymack PP, Anderson FP, Ethridge SF, Jayne EC. Perfor- mance of four homogeneous direct methods for LDL-cholesterol. Clin Chem. 2002;48:489-498. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 54
- Probably not a substantial claim. 9
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“IPE lowered non-HDL-C by 14% (control, 9.8%; active, -5.5%) and apo B by 9% (control, 7%; active, -2.2%).36”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Disputedcites [36] 36. Metkus TS, Timpone J, Leaf D, Bidwell Goetz M, Harris WS, Brown TT. Omega-3 fatty acid therapy reduces triglycerides and interleu- kin-6 in hypertriglyeridemic HIV patients. HIV Med. 2013;14:530-539. doi: 10.1111/hiv.12046 sourceExperimental — accuracy not yet measured
The Methods (Treatment; page unavailable) identify the intervention as Lovaza, an EPA/DHA mixture, not IPE. The Results (Effect of O3A ethyl esters on lipid parameters; page unavailable) report no difference between groups in non-HDL cholesterol or other lipid parameters apart from triglycerides. The copy does not report an apo B reduction or the cited percentages. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Disputed
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Triglyceride reductions from baseline were ≈22% in the 4 g/d O3AEE group and ≈11% for both the O3AEE and IPE 2 g/d groups after 12 weeks”
§ e673 > COMPARISON OF EPA+DHA VERSUS EPA-ONLY AGENTS ON LIPIDS AND LIPOPROTEINS IN INDIVIDUALS WITH HTG
What the sources say
- Disputedcites [52] 52. Shearer GC, Pottala JV, Hansen SN, Brandenburg V, Harris WS. Effects of prescription niacin and omega-3 fatty acids on lipids and vascular func- tion in metabolic syndrome: a randomized controlled trial. J Lipid Res. 2012;53:2429-2435. doi: 10.1194/jlr.P022392 sourceExperimental — accuracy not yet measured
The Methods (Study design; page unavailable) describe a 16-week trial with 60 participants assigned to placebo, 4 g/day prescription omega-3, 2 g/day niacin, or their combination—not the claimed 12-week, approximately 600-patient comparison of O3AEE and IPE doses. The Results (Effects on lipid and lipoprotein levels; page unavailable) report a 13% triglyceride reduction with omega-3 alone, rather than approximately 22%. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
plaindirectn = 600- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Disputed
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Although most trials presented in Table 4 specified direct LDL-C measurement in cases when triglycerides >400 mg/dL (as is standard for clinical practice), only 3 trials reported LDL-C results obtained from direct LDL measurement throughout the triglyceride range.28,30,45”
§ e673 > Writing Group
What the sources say
- Not checked — no full text of the sourcecites [28] 28. Roth EM, Bays HE, Forker AD, Maki KC, Carter R, Doyle RT, Stein EA. Prescription omega-3 fatty acid as an adjunct to fenofibrate therapy in hypertriglyceridemic subjects. J Cardiovasc Pharmacol. 2009;54:196-203. doi: 10.1097/FJC.0b013e3181b0cf71 source
- Not checked — no full text of the sourcecites [30] 30. Grundt H, Nilsen DW, Hetland O, Aarsland T, Baksaas I, Grande T, Woie L. Improvement of serum lipids and blood pressure during intervention with n-3 fatty acids was not associated with changes in insulin levels in subjects with combined hyperlipidaemia. J Intern Med. 1995;237:249-259. doi: 10.111/j.1365-2796.1995.tb01173.x source
- Disputedcites [45] 45. Minihane AM, Khan S, Leigh-Firbank EC, Talmud P, Wright JW, Murphy MC, Griffin BA, Williams CM. ApoE polymorphism and fish oil supplementation in subjects with an atherogenic lipoprotein phenotype. Arterioscler Thromb Vasc Biol. 2000;20:1990-1997. sourceExperimental — accuracy not yet measured
The Biochemical Analysis section states that this trial computed LDL-C using the Friedewald formula, rather than measuring LDL-C directly throughout the triglyceride range. Thus, the paper contradicts its apparent identification as one of the three trials using direct LDL-C measurement. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“The 2011 statement cited epidemiological evidence that a moderate elevation in triglycerides is often associated with increased atherosclerotic cardiovascular disease (ASCVD) risk.”
§ e673 > E
What the sources say
- Supportedcites [1] 1. Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, Kris-Etherton PM, Lennie TA, Levi M, Mazzone T, Pennathur S; on behalf of the American Heart As- sociation Clinical Lipidology, Thrombosis, and Prevention Committee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Car- diovascular Nursing; Council on the Kidney in Cardiovascular Disease. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. source
Section 3.3 (page not available in our copy) reports epidemiological meta-analyses linking higher triglyceride levels with higher CVD risk. The “Elevated Triglyceride Levels” section also describes an association between elevated triglycerides and increased CVD risk. The claim describes an association, not an independent or causal effect. (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“In a 2002 American Heart Association scientific statement, the omega-3 fatty acids (n-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were recommended (at a dose of 2-4 g/d) for reducing triglycerides in patients with elevated triglycerides.”
- Also stated in: § E · plain
“The 2002 AHA scientific statement on fish and n-3 FAs recommended increased dietary omega-3 intake plus dietary supplements to achieve 2 to 4 g/d n-3 FA (referring to the total amount of eicosapentaenoic acid [EPA] plus docosahexaenoic acid [DHA]) for triglyceride-lowering treatment (ie, medical management of HTG) under the supervision of a physician.”
§ e673 > Abstract
What the sources say
- Could not verifycites [12] 12. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC Jr, Sperling L, Virani SS, Yeboah J. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/ AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Circulation. 2019;139:e1182-e1186] sourceExperimental — accuracy not yet measured
The guideline’s Section 3.1 (page not available) discusses triglyceride-lowering drugs but does not mention EPA, DHA, or the claimed dose. Searches of our copy for omega-3 fatty acids, the 2002 AHA statement, and 2–4 g/day found no passage addressing that recommendation. (LLM, conf=0.73)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Also stated in: § E · plain
Every source the paper cites for this claim was checked and supports it.
In the paper
“Because statins are considered to be first-line lipid treatment in patients with HTG, 11 there have been no published monotherapy studies of the more recently available IPE or O3CA in this population.”
§ e673 > n-3 FA as Monotherapy
What the sources say
- Supportedcites [11] 11. Jacobson TA, Maki KC, Orringer CE, Jones PH, Kris-Etherton P, Sikand G, La Forge R, Daniels SR, Wilson DP, Morris PB, Wild RA, Grundy SM, Daviglus M, Ferdinand KC, Vijayaraghavan K, Deedwania PC, Aberg JA, Liao KP, McKenney JM, Ross JL, Braun LT, Ito MK, Bays HE, Brown WV, Underberg JA; NLA Expert Panel. National Lipid Association recommen- dations for patient-centered management of dyslipidemia: part 2. J Clin Lipidol. 2015;9(suppl):S1-122.e1. doi: 10.1016/j.jacl.2015.09.002 source
The paper’s “A High” recommendation identifies moderate- to high-intensity statins as first-line cholesterol-lowering drug therapy. In the citing sentence, the citation follows the statin-treatment premise; the subsequent assertion about the absence of IPE or O3CA monotherapy studies is not attributed to this source. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“On average, the triglyceride reduction was ≈27% (range, 21%-35%), apart from the study of a medical food (3.2 g/d EPA+DHA), which specifically recruited people with very low blood levels of n-3 FA and reported a 48% reduction.”
§ e673 > n-3 FA as Monotherapy
What the sources say
- Partly supportedcites [45] 45. Minihane AM, Khan S, Leigh-Firbank EC, Talmud P, Wright JW, Murphy MC, Griffin BA, Williams CM. ApoE polymorphism and fish oil supplementation in subjects with an atherogenic lipoprotein phenotype. Arterioscler Thromb Vasc Biol. 2000;20:1990-1997. sourceExperimental — accuracy not yet measured
The Results and Discussion (page unavailable) report a 35.3% reduction in fasting triglycerides after fish-oil supplementation in this study, supporting the upper end of the stated range. They do not report a 27% average across monotherapy trials or the medical-food study's 48% reduction in people with very low n-3 fatty acid levels. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“More recent evidence from mendelian randomization studies has shown that elevated triglycerides associated with genetic variants may be a causal factor for ASCVD and possibly for premature all-cause mortality.”
§ e673 > E
What the sources say
- Not checked — no full text of the sourcecites [2] 2. Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lan- cet. 2014;384:626-635. doi: 10.1016/S0140-6736(14)61177-6 source
- Partly supportedcites [3] 3. Stitziel NO. Human genetic insights into lipoproteins and risk of cardiomet- abolic disease. Curr Opin Lipidol. 2017;28:113-119. doi: 10.1097/MOL. 0000000000000389 sourceExperimental — accuracy not yet measured
In the section on triglycerides and coronary artery disease (page not provided), the review discusses Mendelian randomization and genetic variants linking triglyceride-rich lipoproteins to coronary disease risk; its annotated reference 25 explicitly describes evidence for a causal role. Our copy does not report an association with premature all-cause mortality, so that part of the claim is unsupported. (LLM, conf=0.88)
- Partly supportedcites [4] 4. Dewey FE, Gusarova V, Dunbar RL, O'Dushlaine C, Schurmann C, Gottesman O, McCarthy S, Van Hout CV, Bruse S, Dansky HM, Leader JB, Murray MF, Ritchie MD, Kirchner HL, Habegger L, Lopez A, Penn J, Zhao A, Shao W, Stahl N, Murphy AJ, Hamon S, Bouzelmat A, Zhang R, Shumel B, Pordy R, Gipe D, Herman GA, Sheu WHH, Lee IT, Liang KW, Guo X, Rotter JI, Chen YI, Kraus WE, Shah SH, Damrauer S, Small A, Rader DJ, Wulff AB, Nordestgaard BG, Tybjærg-Hansen A, van den Hoek AM, Princen HMG, Ledbetter DH, Carey DJ, Overton JD, Reid JG, Sasiela WJ, Banerjee P, Shuldiner AR, Borecki IB, Teslovich TM, Yancopou sourceExperimental — accuracy not yet measured
The Results section reports that ANGPTL3 loss-of-function carriers had lower triglyceride levels and lower odds of coronary artery disease. That supports a genetic link to coronary disease, but the paper does not establish triglycerides themselves as the causal factor: carriers also had lower LDL and HDL cholesterol. The paper does not report premature all-cause mortality (searched: “premature all-cause mortality”). (LLM, conf=0.84)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In 4 trials, 4 g/d O3AEE averaged a 26% reduction in triglycerides, whereas the reduction in a dietary supplement study of 3 g/d EPA+DHA was 35%.”
§ e673 > n-3 FA as Monotherapy
What the sources say
- Partly supportedcites [44] 44. Bairati I, Roy L, Meyer F. Double-blind, randomized, controlled trial of fish oil supplements in prevention of recurrence of stenosis after coronary an- gioplasty. Circulation. 1992;85:950-956. sourceExperimental — accuracy not yet measured
The Baseline Characteristics section (page not supplied) reports a triglyceride decrease from 2.3 to 1.5 mmol/L at one month—approximately 35%—in the fish-oil group. But the Study Design section specifies 4.5 g/day of EPA+DHA, not 3 g/day, and this single trial does not report an average 26% reduction across four O3AEE trials. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In this trial, DHA increased LDL-C, LDL particle size, and HDL2, but EPA did not.62”
§ e673 > EFFECTS OF EPA-ONLY VERSUS DHA-ONLY ON LIPIDS AND LIPOPROTEINS
What the sources say
- Partly supportedcites [62] 62. Allaire J, Couture P, Leclerc M, Charest A, Marin J, Lépine M-C, Talbot D, Tchernof A, Lamarche B. A randomized, crossover, head-to- head comparison of EPA and DHA supplementation to reduce inflam- mation markers in men and women: the Comparing EPA to DHA (Com- parED) Study. Am J Clin Nutr. 2016;104:280-287. doi: 10.3945/ajcn. 116.131896 sourceExperimental — accuracy not yet measured
The Blood lipids section reports that DHA increased LDL-C more than EPA, but EPA also significantly increased LDL-C versus control (+2.2%). The LCn-3PUFA and plasma lipids section says increased LDL particle size with DHA was an inference requiring measurement. The paper reports increased HDL cholesterol, not specifically HDL2. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This trial also reported an inverse relationship between triglyceride values and LDL particle size, whereas HDL-C was positively correlated with LDL particle size.”
§ e673 > EFFECTS OF EPA-ONLY VERSUS DHA-ONLY ON LIPIDS AND LIPOPROTEINS
What the sources say
- Partly supportedcites [62] 62. Allaire J, Couture P, Leclerc M, Charest A, Marin J, Lépine M-C, Talbot D, Tchernof A, Lamarche B. A randomized, crossover, head-to- head comparison of EPA and DHA supplementation to reduce inflam- mation markers in men and women: the Comparing EPA to DHA (Com- parED) Study. Am J Clin Nutr. 2016;104:280-287. doi: 10.3945/ajcn. 116.131896 sourceExperimental — accuracy not yet measured
The ‘LCn-3PUFA and plasma lipids’ discussion (page unavailable) says that lower triglycerides after DHA supplementation suggest larger LDL particles, but explicitly says this assumption needs verification by measuring LDL particle size. The Blood lipids results (page unavailable) report higher HDL cholesterol with DHA, not a positive correlation between HDL-C and LDL particle size. The trial therefore did not report either correlation as claimed. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“α-Linolenic acid, an 18-carbon plant-derived n-3 FA, has not been shown to reduce triglycerides substantially and is not indicated for the treatment of HTG.65,66”
§ e673 > OTHER N-3 FAs FOR MANAGEMENT OF ELEVATED TRIGLYCERIDES
What the sources say
- Not checked — no full text of the sourcecites [65] 65. Maki KC, Bobotas G, Dicklin MR, Huebner M, Keane WF. Effects of MAT9001 containing eicosapentaenoic acid and docosapentaenoic acid, compared to eicosapentaenoic acid ethyl esters, on triglycerides, lipopro- tein cholesterol, and related variables. J Clin Lipidol. 2017;11:102-109. doi: 10.1016/j.jacl.2016.10.010 Downloaded from http://ahajournals.org by on September 1, 2023 September 17, 2019 Circulation. 2019;140:e673-e691. DOI: 10.1161/CIR.0000000000000709 e690 CLINICAL STATEMENTS AND GUIDELINES source
- Partly supportedcites [66] 66. Wendland E, Farmer A, Glasziou P, Neil A. Effect of alpha linolenic acid on cardiovascular risk markers: a systematic review. Heart. 2006;92:166-169. doi: 10.1136/hrt.2004.053538 sourceExperimental — accuracy not yet measured
The Abstract and “Cholesterol and triglycerides” section report no significant triglyceride reduction with ALA, supporting the first part of the claim. The paper does not address whether ALA is indicated for treating hypertriglyceridemia; its recommendation concerns supplementation to reduce cardiovascular disease. Page numbers were not available in our copy. (LLM, conf=0.87)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“When IPE (4 g/d) was administered with statins, there were placebo-adjusted decreases of 22% in triglycerides, 5% in HDL-C, 14% in non-HDL-C, 9% in apo B, and 6% in LDL-C, 39 and LDL particle size was modestly increased.”
§ e673 > n-3 FA Added to Other Lipid-Lowering Therapies
What the sources say
- Not checked — no full text of the sourcecites [39] 39. Hedengran A, Szecsi PB, Dyerberg J, Harris WS, Stender S. n-3 PUFA es- terified to glycerol or as ethyl esters reduce non-fasting plasma triacylg- lycerol in subjects with hypertriglyceridemia: a randomized trial. Lipids. 2015;50:165-175. doi: 10.1007/s11745-014-3968-6 source
- Partly supportedcites [47] 47. Leigh-Firbank EC, Minihane AM, Leake DS, Wright JW, Murphy MC, Griffin BA, Williams CM. Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential associations with lipid responses. Br J Nutr. 2002;87:435-445. doi: 10.1079/BJNBJN2002556 sourceExperimental — accuracy not yet measured
The Plasma lipids, glucose, insulin section reports lower triglycerides, and the Discussion describes a shift toward larger LDL particles. But this was a trial of 6 g/day fish oil (EPA plus DHA), not 4 g/day IPE with statins; the reported percentages do not match, HDL cholesterol changed little, and LDL cholesterol increased rather than decreased. Our copy gives no corresponding non-HDL cholesterol or apo B reductions. (LLM, conf=0.89)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In addition, n-3 FAs lead to intracellular degradation of apo B, which may be a result of decreased triglyceride availability or autophagic destruction of apo B via post-Golgi oxidation, 90 thereby diminishing the assembly of VLDL particles in the hepatocyte and decreasing VLDL secretion.91,92”
§ e673 > MECHANISMS OF N-3 FA EFFECTS ON LIPOPROTEIN METABOLISM
What the sources say
- Could not verifycites [90] 90. Botolin D, Wang Y, Christian B, Jump DB. Docosahexaneoic acid (22:6,n- 3) regulates rat hepatocyte SREBP-1 nuclear abundance by Erk-and 26S proteasome-dependent pathways. J Lipid Res. 2006;47:181-192. doi: 10.1194/jlr.M500365-JLR200 sourceExperimental — accuracy not yet measured
The Discussion reports that DHA accelerates degradation of nuclear SREBP-1 in rat hepatocytes, not apo B. Searches of our copy for apo B, VLDL assembly and VLDL secretion found no passage addressing the attributed mechanism or its proposed outcome. (LLM, conf=0.75)
- Partly supportedcites [91] 91. Pan M, Maitin V, Parathath S, Andreo U, Lin SX, St Germain C, Yao Z, Maxfield FR, Williams KJ, Fisher EA. Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: a pathway for late-stage quality control. Proc Natl Acad Sci U S A. 2008;105:5862-5867. doi: 10.1073/pnas.0707460104 sourceExperimental — accuracy not yet measured
The Abstract reports that omega-3 PUFAs increase presecretory apoB degradation and inhibit apoB secretion, and the Results describe DHA-induced intracellular aggregation preceding degradation. The Discussion places this destruction late in the secretory pathway, but the paper does not establish that it diminishes VLDL assembly specifically, rather than destroying apoB-containing particles before secretion. (LLM, conf=0.82)
- Partly supportedcites [92] 92. Wang H, Chen X, Fisher EA. N-3 fatty acids stimulate intracellular degra- dation of apoprotein B in rat hepatocytes. J Clin Invest. 1993;91:1380- 1389. doi: 10.1172/JCI116340 sourceExperimental — accuracy not yet measured
The Abstract and the discussion on p. 1387 report that EPA and DHA increased intracellular apoB degradation in rat hepatocytes, accounting for decreased secretion of newly synthesized apoB. The paper does not establish that degradation thereby diminishes VLDL assembly; on p. 1387 it treats interference with assembly as a possible cause of apoB degradation, rather than a demonstrated consequence. (LLM, conf=0.86)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Absorption of the ethyl ester formulations (O3AEE and IPE), although low in a fasting state, is greatly increased by taking them with food, and they are so labeled.93”
§ e673 > Gastrointestinal
What the sources say
- Could not verifycites [93] 93. Maitin V, Andreo U, Guo L, Fisher EA. Docosahexaenoic acid impairs the maturation of very low density lipoproteins in rat hepatic cells. J Lipid Res. 2014;55:75-84. doi: 10.1194/jlr.M043026 sourceExperimental — accuracy not yet measured
The Abstract discusses how DHA and EPA affect apoB degradation, and the Results examine lipoprotein secretion in rat hepatic cells. Searches for O3AEE, IPE, fasting-state absorption, and food effects found no passage addressing the claimed absorption or labeling of these formulations. (LLM, conf=0.76)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Secondary post hoc analyses of previous trials of triglyceride-lowering pharmacotherapy support the finding with the primary but not the key secondary REDUCE-IT end point.102,103”
§ e673 > CARDIOVASCULAR OUTCOME TRIALS OF N-3 FA IN STATIN-TREATED INDIVIDUALS WITH HTG
What the sources say
- Not matchedcites [102] 102. Bhatt DL, Steg PG, Brinton EA, Jacobson TA, Miller M, Tardif JC, Ketchum SB, Doyle RT Jr, Murphy SA, Soni PN, Braeckman RA, Juliano RA, Circulation. 2019;140:e673-e691. DOI: 10.1161/CIR.0000000000000709 September 17, 2019 e691 CLINICAL STATEMENTS AND GUIDELINES
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites [103] 103. Ballantyne CM; REDUCE-IT Investigators. Rationale and design of RE- DUCE-IT: Reduction of Cardiovascular Events with Icosapent Ethyl-Inter- vention Trial. Clin Cardiol. 2017;40:138-148. doi: 10.1002/clc.22692 102. sourceExperimental — accuracy not yet measured
The Discussion reports that subgroup and post hoc analyses of earlier trials suggest possible reductions in major cardiovascular events with triglyceride-lowering therapy. The Methods define the primary and key secondary REDUCE-IT endpoints, but this 2017 design paper does not say those analyses support a finding for the primary endpoint but not the key secondary endpoint; REDUCE-IT follow-up was still ongoing. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, these trials used lower doses (<2 g/d EPA+DHA) 81 or had relatively small sample sizes (<20 participants per study arm) 79,81 that in some cases included patients with only mildly elevated triglycerides.81”
§ e673 > EFFECTS IN CHILDREN AND ADOLESCENTS WITH ELEVATED TRIGLYCERIDES
What the sources say
- Not matchedcites [81] 81. Lovaza (omega-3-acid ethyl esters) [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2009.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites [79] 79. Gidding SS, Prospero C, Hossain J, Zappalla F, Balagopal PB, Falkner B, Kwiterovich P. A double-blind randomized trial of fish oil to lower tri- glycerides and improve cardiometabolic risk in adolescents. J Pediatr. 2014;165:497-503.e2. doi: 10.1016/j.jpeds.2014.05.039 sourceExperimental — accuracy not yet measured
The Methods report 42 adolescents in a crossover trial, supporting the description of a relatively small study, but the available passages do not establish fewer than 20 participants per study arm. The Methods also specify at least 1.5 g DHA plus 1.86 g EPA daily—more than 2 g combined, contrary to the dose attributed to this trial. Enrollment allowed triglycerides from 150 mg/dL, but the Results describe the groups overall as having severely increased triglycerides; they do not establish that participants had only mildly elevated levels. (LLM, conf=0.84)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Some, 107 but not all, 108 supplements also contain unacceptable levels of oxidation products that have been shown to interfere with the beneficial effects of n-3 FAs in some, 109,110 but not all, 111 studies.”
§ e673 > Writing Group
What the sources say
- Not checked — no full text of the sourcecites [107] 107. Ritter JC, Budge SM, Jovica F. Quality analysis of commercial fish oil prep- arations. J Sci Food Agric. 2013;93:1935-1939. doi: 10.1002/jsfa.5994 108. source
- Supportedcites [108] 108. Nichols PD, Dogan L, Sinclair A. Australian and New Zealand fish oil prod- ucts in 2016 meet label omega-3 claims and are not oxidized. Nutrients. 2016;8:E703. doi: 10.3390/nu8110703 109. source
Citation 108 is attached to “but not all” supplements, not to the later claim about effects on benefits. The Results (section 3.2) report that all 10 tested products met the recommended peroxide-value level; the two elevated anisidine readings were attributed to flavorings that interfere with that test. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [109] 109. Rupp TP, Rupp KG, Alter P, Rupp H. Replacement of reduced highly unsatu- rated fatty acids (HUFA deficiency) in dilative heart failure: dosage of EPA/ DHA and variability of adverse peroxides and aldehydes in dietary supple- ment fish oils. Cardiology. 2013;125:223-231. doi: 10.1159/000350656 110. source
- Not checked — no full text of the sourcecites [110] 110. García-Hernández VM, Gallar M, Sánchez-Soriano J, Micol V, Roche E, García-García E. Effect of omega-3 dietary supplements with different oxidation levels in the lipidic profile of women: a random- ized controlled trial. Int J Food Sci Nutr. 2013;64:993-1000. doi: 10.3109/09637486.2013.812619 111. source
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Only 2 trials presented in Table 4 specified avoiding alcohol for at least 48 hours before testing.29,33”
§ e673 > Writing Group
What the sources say
- Not checked — no full text of the sourcecites [29] 29. Mackness MI, Bhatnagar D, Durrington PN, Prais H, Haynes B, Morgan J, Borthwick L. Effects of a new fish oil concentrate on plasma lipids and lipoproteins in patients with hypertriglyceridaemia. Eur J Clin Nutr. 1994;48:859-865.
- Could not verifycites [33] 33. Bays HE, McKenney J, Maki KC, Doyle RT, Carter RN, Stein E. Effects of prescription omega-3-acid ethyl esters on non-high-density lipoprotein cholesterol when coadministered with escalating doses of atorvastatin. Mayo Clin Proc. 2010;85:122-128. doi: 10.4065/mcp.2009.0397 sourceExperimental — accuracy not yet measured
The Patients and Methods section describes eligibility and exclusions, and the End Points passage describes fasting measurements, but neither specifies avoiding alcohol before testing. Searches for alcohol and a 48-hour restriction found no such instruction in our copy. This paper also cannot establish the citing document’s count of two trials in Table 4. (LLM, conf=0.75)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Although it is widely recognized that the Friedewald estimation of LDL-C is inappropriate with triglycerides >400 mg/dL, this estimation progressively loses accuracy even at more modest triglyceride elevations.”
§ e673 > Writing Group
What the sources say
- Partly supportedcites [115] 115. Martin SS, Blaha MJ, Elshazly MB, Toth PP, Kwiterovich PO, Blumenthal RS, Jones SR. Comparison of a novel method vs the Frie- dewald equation for estimating low-density lipoprotein cholesterol lev- els from the standard lipid profile. JAMA. 2013;310:2061-2068. doi: 10.1001/jama.2013.280532 sourceExperimental — accuracy not yet measured
The Results (page unavailable) show that Friedewald estimates of LDL-C below 70 mg/dL agreed progressively less often with direct measurements across triglyceride ranges of 100–149, 150–199, and 200–399 mg/dL. The paper reports its comparison for triglycerides below 400 mg/dL, but the passages do not establish that Friedewald estimation is inappropriate above 400 mg/dL. (LLM, conf=0.86)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
In the paper
“10 weeks of supplementation with 2.7 g/d DHA increased both LDL-C and HDL-C more than 2.7 g/d EPA did, 61 whereas DHA was modestly more effective in reducing triglycerides.61”
§ e673 > EFFECTS OF EPA-ONLY VERSUS DHA-ONLY ON LIPIDS AND LIPOPROTEINS
What the sources say
- Not checked — no full text of the sourcecites [61] 61. Grimsgaard S, Bonaa KH, Hansen JB, Nordøy A. Highly purified eicosapen- taenoic acid and docosahexaenoic acid in humans have similar triacylglyc- erol-lowering effects but divergent effects on serum fatty acids. Am J Clin Nutr. 1997;66:649-659. doi: 10.1093/ajcn/66.3.649 source
plaindirectn = 100- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In 2 older monotherapy studies of dietary supplements (providing 3 and 4.5 g/d total EPA+DHA) that included at least 50 people per arm, a 7% to 8% increase in LDL-C was reported (only marginally significant for the lower dose; P=0.054); however, these studies reported a 35% and 39% reduction in triglycerides. 28,31”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [28] 28. Roth EM, Bays HE, Forker AD, Maki KC, Carter R, Doyle RT, Stein EA. Prescription omega-3 fatty acid as an adjunct to fenofibrate therapy in hypertriglyceridemic subjects. J Cardiovasc Pharmacol. 2009;54:196-203. doi: 10.1097/FJC.0b013e3181b0cf71 source
- Not checked — no full text of the sourcecites [31] 31. Durrington PN, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, France M. An omega-3 polyunsaturated fatty acid concentrate adminis- tered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001;85:544-548. doi: 10.1136/heart.85.5.544 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similarly, in REDUCE-IT, non-HDL-C was reduced by 12.2% (control, 8.2%; active -4.0%) and apo B was reduced by 9.7% (control, 7.8%; active, -2.5%).40”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [40] 40. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, Soni PN. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110:984-92. doi: 10.1016/j.amjcard.2012.05.031 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“With regard to O3CA, the 2-g/d dose examined in the ESPRIT trial (Epanova Combined with a Statin in Patients with Hypertriglyceridemia to Reduce Non-HDL Cholesterol; ≈1.5 g/d EPA+DHA) reduced triglycerides by 9% versus 15% with 4 g/d.41”
§ e673 > DOSING CONSIDERATIONS
What the sources say
- Not checked — no full text of the sourcecites [41] 41. Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11-22. doi: 10.1056/NEJMoa1812792 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In a 2-week open-label crossover comparison of 4 g/d MAT9001 (containing unspecified amounts of free docosapentaenoic acid and EPA) versus 4 g/d IPE in people with HTG, plasma triglycerides were reduced 33% by MAT9001, which was significantly more than the 11% reduction with IPE.64”
§ e673 > OTHER N-3 FAs FOR MANAGEMENT OF ELEVATED TRIGLYCERIDES
What the sources say
- Not checked — no full text of the sourcecites [64] 64. Maki KC, Keane WF, Bouhajib M, Pop R, Bobotas G. Pharmacokinetics of MAT9001, an omega-3 fatty acid medication, compared with eicos- apentaenoic acid ethyl esters in hypertriglyceridemic subjects. FASEB J. 2016;30(suppl):1198.7. Abstract. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“O3CA lowered non-HDL-C by 6% and apo B by 2%, 41”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [41] 41. Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11-22. doi: 10.1056/NEJMoa1812792 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Use of n-3 FA may be accompanied by mild gastrointestinal complaints (such as”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“the product inserts suggest substantial differences in the rates of gastrointestinal side effects for each agent relative to placebo: O3CA, 27% versus 8%; O3AEE, 3% to 4% versus <1% to 2%; and IPE, <1% to 7% versus 4% to 7% for active agent compared with placebo, respectively.”
§ e673 > Gastrointestinal
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“n-3 FAs are highly purified oils and do not appear to be allergenic.97”
§ e673 > Bleeding
What the sources say
- Not checked — no full text of the sourcecites [97] 97. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; Japan EPA Lipid Intervention Study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open- label, blinded endpoint analysis. Lancet. 2007;369:1090-1098. doi: 10.1016/S0140-6736(07)60527-3 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Risk for each of the individual components of the primary composite end point was also significantly reduced, including a 20% reduction in cardiovascular death.”
§ e673 > CARDIOVASCULAR OUTCOME TRIALS OF N-3 FA IN STATIN-TREATED INDIVIDUALS WITH HTG
What the sources say
- Not checked — no full text of the sourcecites [40] 40. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, Soni PN. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110:984-92. doi: 10.1016/j.amjcard.2012.05.031 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“studies of 4 g/d EPA+DHA or EPA-only as adjuncts to statin therapy, non-HDL-C and apo B were modestly decreased, suggesting reductions in total atherogenic lipoproteins.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“but taking n-3 FA with meals may reduce gastrointestinal side effects and improve absorption of O3AEE and IPE.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“REDUCE-IT did not find an increase in hemoglobin A 1c or in new-onset diabetes mellitus.40”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [40] 40. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, Soni PN. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110:984-92. doi: 10.1016/j.amjcard.2012.05.031 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In clinical trials of prescription n-3 FA agents, tolerability issues have generally been relatively minor (see sections titled Gastrointestinal, Bleeding, Fish/Seafood Allergies, and Glycemic Control) and resulted in drug discontinuation in only a small percentage of subjects (usually <5%).”
§ e673 > SAFETY AND TOLERABILITY OF PRESCRIPTION N-3 FA PRODUCTS General
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Notably, lipid effects were consistent with earlier IPE trials, with a placebo-adjusted triglyceride reduction of 20% at assessments at 4 months to 3 years and changes in non-HDL-C of -12.2% (control, 8.2%; active, -4.0%), in LDL-C of -6.6% (control, 10.2%; active, 3.1%), in apo B of -9.7% (control, 7.8%; active, -2.5%), and in HDL-C of -7.2% (control, 4.7%; active, -2.8%).”
§ e673 > CARDIOVASCULAR OUTCOME TRIALS OF N-3 FA IN STATIN-TREATED INDIVIDUALS WITH HTG
What the sources say
- Not checked — no full text of the sourcecites [40] 40. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, Soni PN. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110:984-92. doi: 10.1016/j.amjcard.2012.05.031 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similarly, REDUCE-IT reported a trend toward an increase in bleeding events (2.7% vs 2.1%; P=0.06) but no significant increase for any site (gastrointestinal, central nervous system, or other), and there were no fatal bleeding events in the trial.40”
§ e673 > Bleeding
What the sources say
- Not checked — no full text of the sourcecites [40] 40. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, Soni PN. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110:984-92. doi: 10.1016/j.amjcard.2012.05.031 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“there was a small but statistically significant increase in total hemorrhagic events (cerebral, fundal, epistaxis, or subcutaneous; 1.1% for EPA versus 0.6% for control; P=0.0006), although no significant increase was reported for cerebral hemorrhage as a single hemorrhagic outcome.96”
§ e673 > Bleeding
What the sources say
- Not checked — no full text of the sourcecites [96] 96. Harris WS. Fish oils and bleeding: where is the evidence? JAMA Intern Med. 2016;176:1405-1406. doi: 10.1001/jamainternmed.2016.3968 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In contrast, neither IPE 21 nor O3CA 22 significantly changed HDL-C.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [21] 21. Pownall HJ, Brauchi D, Kilinç C, Osmundsen K, Pao Q, Payton-Ross C, Gotto AM Jr, Ballantyne CM. Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipopro- teins. Atherosclerosis. 1999;143:285-297. doi: https://doi.org/10.1016/ S0021-9150(98)00301-3 source
- Not checked — no full text of the sourcecites [22] 22. Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. Eicosapentaenoic acid ethyl ester (AMR101) therapy in pa- tients with very high triglyceride levels (from the Multi-center, plAcebo- controlled, Randomized, double-blINd, 12-week study with an open- label Extension [MARINE] trial). Am J Cardiol. 2011;108:682-690. doi: 10.1016/j.amjcard.2011.04.015 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Fibrates, the most commonly used drug class (especially fenofibrate), lower triglycerides by 15% to 60%, with efficacy depending primarily on the baseline triglyceride level.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not matchedcites [16] 16. Herink M, Ito MK. Medication induced changes in lipid and lipopro- teins. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, eds. Endotext. South Dartmouth, MA: MDText. com, Inc; 2000. Accessed December 5, 2018.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim have been checked yet.
In the paper
“Ezetimibe and proprotein con-vertase subtilisin kexin type 9 monoclonal antibodies have minimal to modest effects and are not indicated for triglyceride lowering.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not matchedcites [17] 17. Robinson JG. Clinical Lipid Management. 1st ed. West Islip, NY: Profes- sional Communications, Inc; 2016.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [18] 18. Guyton JR, Bays HE. Safety considerations with niacin therapy. Am J Car- diol. 2007;99:22C-31C. doi: 10.1016/j.amjcard.2006.11.018 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“n-3 FAs with EPA+DHA or with EPA-only appear roughly comparable for triglyceride lowering and do not increase low-density lipoprotein cholesterol when used as monotherapy or in combination with a statin.”
§ e673 > Abstract
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The degree of triglyceride lowering with full-dose prescription n-3 FA (4 g/d providing >3 g/d EPA+DHA) appears to be similar to that of fibrates, although studies directly comparing these 2 drug classes in patients with VHTG are lacking.”
§ e673 > EFFECTS OF PRESCRIPTION N-3 FA AT FDA-APPROVED DOSES IN INDIVIDUALS WITH VHTG (≥500 MG/DL)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In patients with VHTG (triglycerides, 500-2000 mg/dL), treatment with IPE did not raise LDL-C, and apo B decreased, suggesting differing effects from those of EPA+DHA.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [21] 21. Pownall HJ, Brauchi D, Kilinç C, Osmundsen K, Pao Q, Payton-Ross C, Gotto AM Jr, Ballantyne CM. Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipopro- teins. Atherosclerosis. 1999;143:285-297. doi: https://doi.org/10.1016/ S0021-9150(98)00301-3 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To evaluate and summarize the existing clinical evidence for n-3 FA effects on HTG, we identified and compared studies meeting the following criteria: administration of 4 g/d prescription n-3 FA or an equivalent amount of EPA+DHA from dietary supplements (>3 g/d EPA+DHA), mean/median baseline triglyceride values between 200 and 499 mg/dL, results reported from at least 20 people per study arm, and”
§ e673 > EFFICACY OF N-3 FA AT FDA-APPROVED DOSES IN INDIVIDUALS WITH HTG (200-499 MG/DL)
plainn = 20- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The studies of O3AEE in VHTG were of monotherapy with no background statin use, whereas more recent studies of IPE and O3CA in VHTG included subjects taking statins (25% and 33% of the study population, respectively).”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [21] 21. Pownall HJ, Brauchi D, Kilinç C, Osmundsen K, Pao Q, Payton-Ross C, Gotto AM Jr, Ballantyne CM. Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipopro- teins. Atherosclerosis. 1999;143:285-297. doi: https://doi.org/10.1016/ S0021-9150(98)00301-3 source
- Not checked — no full text of the sourcecites [22] 22. Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. Eicosapentaenoic acid ethyl ester (AMR101) therapy in pa- tients with very high triglyceride levels (from the Multi-center, plAcebo- controlled, Randomized, double-blINd, 12-week study with an open- label Extension [MARINE] trial). Am J Cardiol. 2011;108:682-690. doi: 10.1016/j.amjcard.2011.04.015 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Highintensity statins and niacin also may have substantial triglyceride-lowering effects, which are proportional to baseline triglycerides.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In patients treated with a combination of 130 mg/d fenofibrate and 4 g/d O3AEE, triglyceride lowering of 61% was observed, which was only marginally better (P=0.06)than the 54% reduction achieved with fenofibrate alone.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [27] 27. Maki KC, McKenney JM, Reeves MS, Lubin BC, Dicklin MR. Effects of add- ing prescription omega-3 acid ethyl esters to simvastatin (20 mg/day) on lipids and lipoprotein particles in men and women with mixed dyslipidemia. Am J Cardiol. 2008;102:429-433. doi: 10.1016/j.amjcard.2008.03.078 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We conclude that prescription n-3 FAs (EPA+DHA or EPA-only) at a dose of 4 g/d (>3 g/d total EPA+DHA) are an effective and safe option for reducing triglycerides as monotherapy or as an adjunct to other lipid-lowering agents.”
§ e673 > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The effects of n-3 fatty acids on triglycerides and lipoproteins observed in the reviewed trials apply to the broader population of patients with elevated triglycerides.
In the paper
“Relative to baseline, the combination of fenofibrate and O3AEE resulted in LDL-C increases of 52%, although non-HDL-C significantly decreased by 7% and apo B was unchanged.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
What the sources say
- Not checked — no full text of the sourcecites [27] 27. Maki KC, McKenney JM, Reeves MS, Lubin BC, Dicklin MR. Effects of add- ing prescription omega-3 acid ethyl esters to simvastatin (20 mg/day) on lipids and lipoprotein particles in men and women with mixed dyslipidemia. Am J Cardiol. 2008;102:429-433. doi: 10.1016/j.amjcard.2008.03.078 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In a third study, in which all patients were on a stable dose of statin before beginning O3AEE treatment, there was a 25% reduction in triglycerides and a marginally significant increase in LDL-C relative to placebo (median, 3.5% increase; P=0.052).”
§ e673 > n-3 FA Added to Other Lipid-Lowering Therapies
What the sources say
- Not checked — no full text of the sourcecites [31] 31. Durrington PN, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, France M. An omega-3 polyunsaturated fatty acid concentrate adminis- tered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001;85:544-548. doi: 10.1136/heart.85.5.544 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Of the 5 O3AEE studies, 2 administered O3AEE in combination with statin therapy as part of the trial design, 26,32 and triglycerides were reduced 17% to 19% beyond the reduction achieved by statins, non-HDL-C was decreased 5% to 7%, and LDL-C was unchanged versus the statin-only control.”
§ e673 > n-3 FA Added to Other Lipid-Lowering Therapies
What the sources say
- Not checked — no full text of the sourcecites [26] 26. Maki KC, Bays HE, Dicklin MR, Johnson SL, Shabbout M. Effects of prescription omega-3-acid ethyl esters, coadministered with atorv- astatin, on circulating levels of lipoprotein particles, apolipoprotein CIII, and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia. J Clin Lipidol. 2011;5:483-492. doi: 10.1016/j.jacl.2011.09.001 source
- Not checked — no full text of the sourcecites [32] 32. Davidson MH, Stein EA, Bays HE, Maki KC, Doyle RT, Shalwitz RA, Ballantyne CM, Ginsberg HN; COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double- blind, placebo-controlled study. Clin Ther. 2007;29:1354-1367. doi: 10.1016/j.clinthera.2007.07.018 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that purified DHA may modestly increase LDL-C and HDL-C more than purified EPA but may also lower triglycerides more than EPA.”
§ e673 > EFFECTS OF EPA-ONLY VERSUS DHA-ONLY ON LIPIDS AND LIPOPROTEINS
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The unusual placebo effect on LDL-C in the 2 IPE trials and the lack of trials directly comparing the 3 prescription n-3 FA agents prevent the drawing of any firm conclusions about the comparative effects of these agents on triglycerides, LDL-C, and other lipids and lipoproteins.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the context of HTG (triglycerides, 200-499 mg/dL), 4 g/d prescription n-3 FA effectively lowers triglycerides by ≈20% to 30% and does not significantly increase LDL-C.”
§ e673 > SUMMARY AND CONCLUSIONS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On the basis of available data, all prescription agents appear comparably effective, but head-to-head comparisons are lacking”
§ e673 > SUMMARY AND CONCLUSIONS
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Prescription n-3 FA at a dose of 4 g/d has consistently produced significant reductions in triglyceride levels in patients with HTG or VHTG, and this effect is greater in patients with VHTG than in those with HTG (as for triglyceride-lowering agents in general).”
§ e673 > SUMMARY OF LIPID EFFECTS FOR N-3 FA AT FDA-APPROVED PRESCRIPTION DOSES
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All forms of n-3 FA products have relatively benign side-effect profiles and are generally safe; however, the evidence for safety of FDA-approved prescription n-3 FA agents comes primarily from short-term randomized clinical trials.”
§ e673 > SAFETY AND TOLERABILITY OF PRESCRIPTION N-3 FA PRODUCTS General
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Prescription n-3 FAs at doses of 2 g/d provided roughly one-half the triglyceride-lowering efficacy of 4 g/d, the former in some cases not differing significantly from placebo.”
§ e673 > CLINICAL STATEMENTS AND GUIDELINES
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Such an approach has been recommended by the National Lipid Association 10 and International Atherosclerosis Society 117 for patients with HTG or VHTG.”
§ e673 > Writing Group
What the sources say
- Not checked — no full text of the sourcecites [10] 10. Ewald N, Hardt PD, Kloer HU. Severe hypertriglyceridemia and pancreati- tis: presentation and management. Curr Opin Lipidol. 2009;20:497-504. doi: 10.1097/MOL.0b013e3283319a1d source
- Not checked — no full text of the sourcecites [117] 117. Expert Panel on Dyslipidemia. An International Atherosclerosis So- ciety position paper: global recommendations for the manage- ment of dyslipidemia. Atherosclerosis. 2014;232:410-413. doi: 10.1016/j.atherosclerosis.2013.11.031 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because of the problems with typical measurement and interpretation of LDL-C levels in clinical care, non-HDL-C is preferred over LDL-C as a parameter of atherogenic lipids to guide therapy in patients with HTG and VHTG.”
§ e673 > Writing Group
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper relies on this without support.
The reviewed trials are sufficiently comparable that their results can be combined or compared to summarize the effects of prescription n-3 fatty acids in hypertriglyceridemia and very high triglycerides.
“To evaluate and summarize the existing clinical evidence for n-3 FA effects on HTG, we identified and compared studies meeting the following criteria: administration of 4 g/d prescription n-3 FA or an equivalent amount of EPA+DHA from dietary supplements (>3 g/d EPA+DHA), mean/median baseline triglyceride values between 200 and 499 mg/dL, results reported from at least 20 people per study arm, and”
The paper relies on this without support.
The effects of n-3 fatty acids on triglycerides and lipoproteins observed in the reviewed trials apply to the broader population of patients with elevated triglycerides.
“We conclude that prescription n-3 FAs (EPA+DHA or EPA-only) at a dose of 4 g/d (>3 g/d total EPA+DHA) are an effective and safe option for reducing triglycerides as monotherapy or as an adjunct to other lipid-lowering agents.”
The paper relies on this without support.
The REDUCE-IT result with EPA-only can support the use of n-3 fatty acids generally for improving atherosclerotic cardiovascular disease risk in patients with hypertriglyceridemia.
“The use of n-3 FA (4 g/d) for improving atherosclerotic cardiovascular disease risk in patients with hypertriglyceridemia is supported by a 25% reduction in major adverse cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With EPA Intervention Trial), a randomized placebo-controlled trial of EPA-only in high-risk patients treated with a statin.”
The paper relies on this without support.
The lipid effects reported across different trials can be compared despite differences in populations, background therapies, and assay methods.
“However, a descriptive comparison of the triglyceride and LDL-C effects in major studies of the 3 n-3 FA agents in patients with HTG is shown in the Figure.31,[39][40][41]”
The paper relies on this without support.
No FDA-regulated n-3 FA preparations are available without a prescription.
“there are no over-the-counter n-3 FA products; that is, no FDA-regulated n-3 FA preparations are available without a prescription.”
The paper relies on this without support.
The potency, quality, and efficacy of dietary supplements are not initially reviewed or approved, nor subsequently monitored or assured by the FDA, so they are not indicated for the treatment of disease.
“The potency, quality, and efficacy of dietary supplements are not initially reviewed or approved, nor are they subsequently monitored or assured by the FDA; thus, they are not indicated for the treatment of disease.”
The paper relies on this without support.
Prescription n-3 FA agents are reviewed, approved, monitored, and assured by the FDA.
“Prescription n-3 FA agents, in contrast, are reviewed, approved, monitored, and assured by the FDA.”
The paper relies on this without support.
Dietary supplement omega-3 preparations are considerably less expensive per 1 g EPA+DHA than pharmaceutical products.
“Dietary supplement omega-3 preparations are considerably less expensive (per 1 g EPA+DHA) than pharmaceutical products”
The paper relies on this without support.
Many n-3 FA dietary supplements meet all their label claims and do not contain oxidation products or environmental contaminants.
“Although many n-3 FA dietary supplements meet all their label claims and do not contain oxidation products or environmental contaminants”
The paper relies on this without support.
Dietary supplement n-3 FA products are not indicated for the treatment of HTG or VHTG because they are not approved by the FDA for this purpose.
“these products are not indicated for the treatment of HTG or VHTG because they are not approved by the FDA for this purpose.”
The authors state this as an assumption.
The Friedewald equation assumes a constant triglycerides/cholesterol ratio of 5 in VLDL regardless of plasma triglyceride concentration.
“The Friedewald equation assumes a constant triglycerides/cholesterol ratio of 5 in VLDL, regardless of the plasma triglyceride concentration.”
The paper relies on this without support.
As total plasma triglyceride increases, the triglycerides carried by VLDL increase disproportionately to its cholesterol content.
“As total plasma triglyceride increases, the triglycerides carried by VLDL increase disproportionately to its cholesterol content.”
The paper relies on this without support.
Patients with HTG may have delayed postprandial clearance of chylomicrons.
“because patients with HTG (in addition to VHTG) may have delayed postprandial clearance of chylomicrons”
The paper relies on this without support.
No published data directly compare fasting and nonfasting triglycerides in the same patients.
“no published data directly compare fasting and nonfasting triglycerides in the same patients”
The paper relies on this without support.
Standard reference ranges do not currently exist for nonfasting triglyceride values.
“standard reference ranges do not currently exist for nonfasting triglyceride values”
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?
The cited source doesn’t support the claim as written.
In the citing paper
“The latter study was terminated for futility, and so far, data remain unpublished and thus difficult to speculate on.”
From Effects of n-3 Fatty Acid Supplements in Elderly Patients After Myocardial Infarction (2021) · cites this paper as [36]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In light of the strong results in REDUCE-IT, several national and international guidelines have incorporated icosapent ethyl into their recommendations.10–13”
From REDUCE-IT USA: Results From the 3146 Patients Randomized in the United States (2020) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Omega-3 PUFAs in doses of 2 to 4 g/day typically lower blood triglyceride levels by 25% to 40%.”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [19]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The American Heart Association scientific statements currently recommend n-3 PUFA supplements for secondary prevention of coronary heart disease 15 and in management of hypertriglyceridemia 16 .”
From Effects of n-3 Fatty Acid Supplements in Elderly Patients After Myocardial Infarction (2021) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The lack of effects on ALT, HDL, and LDL may reflect the selective action of omega-3 fatty acids. Their lipid-lowering effects primarily target the triglyceride metabolic pathway, including promoting fatty acid oxidation and reducing lipogenesis by activating PPAR-α and inhibiting SREBP-1c,42,43 while exerting weaker direct effects on cholesterol reverse transport and synthesis.44,45”
From The Impact of Omega-3 Fatty Acids on Triglyceride Levels in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Meta-Analysis of Randomized Controlled Trials with Subgroup Analysis by Diabetes Status (2026) · cites this paper as [42]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Because the magnitude of the absolute effect is a function of both baseline risk and ef fi cacy of therapy, patients with higher baseline cardiovascular risk and those receiving higher doses of omega-3 FAs may demonstrate incremental absolute event reductions [12,13,18].”
From Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis (2021) · cites this paper as [18]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Because the magnitude of the absolute effect is a function of both baseline risk and ef fi cacy of therapy, patients with higher baseline cardiovascular risk and those receiving higher doses of omega-3 FAs may demonstrate incremental absolute event reductions [12,13,18].”
From Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis (2021) · cites this paper as [18]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“After REDUCE-IT, several national and international guidelines endorsed EPA in their therapeutic recommendations [18,34].”
From Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis (2021) · cites this paper as [18]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For patients with elevated triglycerides, 4 grams per day of EPA + DHA is recommended, an amount that requires pharmacotherapy to achieve a consistent dose on an ongoing basis (89).”
From 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia (2021) · cites this paper as [89]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“at higher doses (2 to 4 g/day), fish oil dietary supplements have been used to lower triglycerides”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [19]
The cited source says what the claim attributes to it.
In the citing paper
“Nevertheless, the dosage used in OMEMI was about twice that used in comparable earlier trials 5, 7, 23, 30 , although considerably lower than the dosage used in REDUCE-IT 14 , and also in the STRENGTH trial 36 .”
From Effects of n-3 Fatty Acid Supplements in Elderly Patients After Myocardial Infarction (2021) · cites this paper as [36]
The cited source says what the claim attributes to it.
In the citing paper
“which is less than previous n-3 PUFA studies in patients who were younger and with higher baseline triglyceride levels 36 .”
From Effects of n-3 Fatty Acid Supplements in Elderly Patients After Myocardial Infarction (2021) · cites this paper as [36]
In the citing paper
“there are now prescription omega-3 PUFAs, which have been approved by the U.S. Food and Drug Administration for this indication”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [19]
In the citing paper
“Neither fish oil dietary supplements nor prescription omega-3 PUFAs have been proven to lower the risk of chylomicron syndrome or pancreatitis, owing to lack of trial data.”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [19]
In the citing paper
“approximately 10% per 1 g of EPA or DHA”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [19]
In the citing paper
“The mechanisms by which omega-3 PUFAs lower triglycerides reflects, in part, increased uptake into cellular phospholipids, rather than into triacylglycerol, due to inhibition of phosphatidic acid phosphatase”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [19]
In the citing paper
“High-dose DHA and EPA (4 g/day) typically lower triglycerides by 20% to 30%, with higher reductions in patients with more severe hypertriglyceridemia”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [19]
In the citing paper
“Omega-3 PUFAs are well tolerated, and side effects occur typically in <5% of persons”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [19]
In the citing paper
“The American Heart Association (AHA) recently issued a science advisory on OM-3s for treatment of hypertriglyceridemia, stating that Rx OM-3s, at 4 g/day, produce TG reductions of approximately 20–30% in patients with high TG (200–499 mg/dl) and reductions of ≥ 30% in those with higher TG (≥ 500 mg/dl), noting LDL-C increases with DHA-containing products in the latter group [21].”
From Critical Differences Between Dietary Supplement and Prescription Omega-3 Fatty Acids: A Narrative Review (2020) · cites this paper as [21]
In the citing paper
“The 2019 AHA advisory concluded that Rx OM-3s (DHA + EPA or EPA-only) are clinically useful for reducing TG after any underlying causes have been addressed and diet and lifestyle strategies implemented, either as monotherapy or an adjunct to other TG-lowering therapies [21].”
From Critical Differences Between Dietary Supplement and Prescription Omega-3 Fatty Acids: A Narrative Review (2020) · cites this paper as [21]
In the citing paper
“The American Heart Association (AHA) recently issued a science advisory on OM-3s for treatment of hypertriglyceridemia, stating that Rx OM-3s, at 4 g/day, produce TG reductions of approximately 20–30% in patients with high TG (200–499 mg/dl) and reductions of ≥ 30% in those with higher TG (≥ 500 mg/dl), noting LDL-C increases with DHA-containing products in the latter group [21].”
From Critical Differences Between Dietary Supplement and Prescription Omega-3 Fatty Acids: A Narrative Review (2020) · cites this paper as [21]
In the citing paper
“The American Heart Association (AHA) recently issued a science advisory on OM-3s for treatment of hypertriglyceridemia, stating that Rx OM-3s, at 4 g/day, produce TG reductions of approximately 20–30% in patients with high TG (200–499 mg/dl) and reductions of ≥ 30% in those with higher TG (≥ 500 mg/dl), noting LDL-C increases with DHA-containing products in the latter group [21].”
From Critical Differences Between Dietary Supplement and Prescription Omega-3 Fatty Acids: A Narrative Review (2020) · cites this paper as [21]
In the citing paper
“The AHA concluded that prescription of n-3 fatty acids (EPA + DHA or EPA-only) at a dose of 4 g/day (> 3 g/day total EPA + DHA) would be an effective and safe option for reducing triglycerides, either as a monotherapy or as an adjunct to other lipid-lowering agents.”
From Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: Review of recent studies and recommendations (2021) · cites this paper as [43]
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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ e673 > n-3 FA as Monotherapy
“Six published trials in which 3 to 4 g/d n-3 FA was administered to people with HTG not taking other lipidlowering medications were identified as meeting the inclusion criteria listed above.28,29,33,36,[44][45][46]”
§ e673 > n-3 FA Added to Other Lipid-Lowering Therapies
“Shaikh et al, 45 2014 (Canada) Parallel 8 wk Statin (20%) Omega Score (EPA+DPA+DHA in whole blood) <6% 3.2 (2.7 EPA, 0.4 DHA)”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ e673 > DOSING CONSIDERATIONS
“Regardless of the type of agent, 4 g/d prescription n-3 FA agents (providing >3 g/d EPA+DHA) have consistently reduced triglyceride levels in patients with elevated triglycerides.”
§ e673 > Writing Group
“iv.Epanova: 550 mg EPA and 200 mg DHA fatty acid per 1000mg capsule (ie, 75% EPA+DHA; no correction necessary for this non-ethyl ester, carboxylic acid product), 3 g EPA+DHA per 4-g dose”
Citations
Cites
Friedewald, W. T., Levy, R. I., & Fredrickson, D. S. (1972) · Clinical Chemistry · doi:10.1093/clinchem/18.6.499 · Cited by 32,423
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Grundy, S. M., Stone, N. J., Bailey, A. L., Beam, C., Birtcher, K. K., Blumenthal, R. S., Braun, L. T., de Ferranti, S., Faiella-Tommasino, J., Forman, D. E., et al. (2019) · Circulation · doi:10.1161/cir.0000000000000625 · Cited by 6,185
Self-citationFish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease
Kris-Etherton, P. M., Harris, W. S., & Appel, L. J. (2002) · Circulation · doi:10.1161/01.cir.0000038493.65177.94 · Cited by 3,707
Self-citationJournal of Biological Chemistry
Kurkinensp, M., CondongT, M. R., Blumberg, B., Barlow, D. P., Quiñones, S., Sausg, J., & Pihlajaniemisyy, T. (2021) · Journal of Biological Chemistry · doi:10.1074/jbc · Cited by 3,427
Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia
Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Doyle, R. T., Juliano, R. A., Jiao, L., Granowitz, C., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812792 · Cited by 3,317
Self-citationYokoyama, M., Origasa, H., Matsuzaki, M., Matsuzawa, Y., Saito, Y., Ishikawa, Y., Oikawa, S., Sasaki, J., Hishida, H., Itakura, H., et al. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60527-3 · Cited by 2,516
Nordestgaard, B. G., Benn, M., Schnohr, P., & Tybjærg-Hansen, A. (2007) · JAMA · doi:10.1001/jama.298.3.299 · Cited by 2,058
Triglycerides and Cardiovascular Disease: A Scientific Statement From the American Heart Association
Miller, M., Stone, N. J., Ballantyne, C., Bittner, V., Criqui, M. H., Ginsberg, H. N., Goldberg, A. C., Howard, W. J., Jacobson, M. S., Kris-Etherton, P. M., et al. (2011) · Circulation · doi:10.1161/cir.0b013e3182160726 · Cited by 1,871
Self-citationFasting compared with nonfasting triglycerides and risk of cardiovascular events in women
Bansal, S., Buring, J. E., Rifai, N., Mora, S., Sacks, F. M., & Ridker, P. M. (2007) · JAMA · doi:10.1001/jama.298.3.309 · Cited by 1,619
Research works printed but not linked: 1
- Robinson, JG. Clinical Lipid Management. 1st ed. West Islip, NY: Professional Communications, Inc; 2016.
Cited by
Sorted by citations
Ginsberg, H. N., Packard, C. J., Chapman, M. J., Borén, J., Aguilar-Salinas, C. A., Averna, M., Ference, B. A., Gaudet, D., Hegele, R. A., Kersten, S., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab551 · Cited by 979
Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease
Abdelhamid, A. S., Brown, T. J., Brainard, J. S., Biswas, P., Thorpe, G., Moore, H. J., Deane, K. H., AlAbdulghafoor, F. K., Summerbell, C., Worthington, H. V., et al. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003177.pub3 · Cited by 647
Soppert, J., Lehrke, M., Marx, N., Jankowski, J., & Noels, H. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.07.019 · Cited by 440
Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis
Khan, S. U., Lone, A. N., Khan, M. S., Virani, S. S., Blumenthal, R. S., Nasir, K., Miller, M., Michos, E. D., Ballantyne, C. M., Boden, W. E., et al. (2021) · eClinicalMedicine · doi:10.1016/j.eclinm.2021.100997 · Cited by 411
“After REDUCE-IT, several national and international guidelines endorsed EPA in their therapeutic recommendations [18,34].”
BackgroundSelf-citationMarine Omega-3 (N-3) Fatty Acids for Cardiovascular Health: An Update for 2020
Innes, J. K., & Calder, P. C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041362 · Cited by 408
Metadata
- Authors
- Skulas-Ray, A. C., Wilson, P. W. F., Harris, W. S., Brinton, E. A., Kris-Etherton, P. M., Richter, C. K., Jacobson, T. A., Engler, M. B., Miller, M., Robinson, J. G., Blum, C. B., Rodriguez-Leyva, D., de Ferranti, S. D., Welty, F. K., & On behalf of the American Heart Association Council on Arteriosclerosis, T. A. V. B. C. O. L. A. C. H. C. O. C. D. I. T. Y. C. O. C. A. S. N. A. C. O. C. C.
- Affiliations
- United States Department of Health and Human Services (US)
- Uniformed Services University of the Health Sciences (US)
- ORCID
- Venue
- Circulation
- Published
- 2019-09-17
- Volume
- 140
- Issue
- 12
- Pages
- e673-e691
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2969523838
- Semantic Scholar
- ac70ecb78df51c94dbc3f1040f152c15e0b86612
- Cited by
- 512
- References
- 120
- Citations by year
- 2026: 65 · 2025: 67 · 2024: 59 · 2023: 89 · 2022: 70 · 2021: 64 · 2020: 86 · 2019: 11
- FWCI
- 43.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- U.S. Department of Health and Human Services
- National Institutes of Health
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- omega-3 fatty acids, hypertriglyceridemia, eicosapentaenoic acid, docosahexaenoic acid, triglyceride lowering, LDL cholesterol, non-HDL cholesterol, apolipoprotein B, atherosclerotic cardiovascular disease risk, REDUCE-IT trial, statin combination therapy
- MeSH terms
- American Heart Association, Cardiovascular Diseases, Clinical Trials as Topic, Humans, Risk, Triglycerides, United States, Hypertriglyceridemia, Fatty Acids, Omega-3, Atherosclerosis
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.
A language model drew the claims from the paper on 2026-09-30, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-09-30 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
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