Protocol · graded by use, three uses
Seed oils: linoleic-acid vegetable oils in place of saturated fat
LDL Low-density lipoprotein cholesterol, the cholesterol fraction most closely tied to plaque in the arteries. and total cholesterol when linoleic-acid oils replace saturated fat.
At a glance
Seed oils are oils like corn, soybean, sunflower and safflower oil. In the trials, people used these oils instead of butter, lard and other hard fats. Their bad cholesterol went down. Whether that meant fewer heart attacks depends on which trials you count. Deaths from any cause did not change. Trials that checked for inflammation in the blood did not find it went up.
- What was measured
- LDL cholesterol in the blood, and in longer trials, heart attacks and deaths.
- How big
- Swapping in these oils lowered LDL cholesterol by 11% and total cholesterol by 9% more than the comparison diet.Read from the summary of PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 27737722.
- Who it applies to
- Adults with mildly raised cholesterol, not on statins, in trials lasting weeks to years.
- Safety
- Inflammation markers did not rise. In one old trial in men after a heart attack, more died on the oil diet.
- Compared with
- Diets that kept the saturated fat, such as butter, lard and fatty meat.
- Certainty
- Grade B, resting on: Meta-analyses A study that pools the numbers from several trials into one combined estimate. of randomized diet trials, recovered data from two 1960s and 1970s randomized trials, and randomized feeding trials of blood lipids and inflammatory markers; cohort studies An observational study that follows a group of people over time and compares what happens to them. and a non-randomized hospital trial are listed as excluded evidence and carry no letter.
- What would change this grade
- Could rise to A with: Randomized trial of linoleic-acid oil against saturated fat with the rest of the diet held equal, and a third arm of olive oil. Who: Adults at raised cardiovascular risk, several thousand per arm. Measured: Cardiovascular events and all-cause death, with LDL and inflammatory markers measured along the way. Length: At least 5 years.
- Cost
- No price recorded yet.
- Sources
- 18 studies cited on this record, listed under Sources.
The B belongs to one of the three uses graded on this record. The other two carry their own letters.
This record carries a separate letter for each thing it has been measured on. The headline grade is the best of them, and it does not transfer to the others.
Schwingshackl et al. (2018; PMID 30006369), network meta-analysis of 54 randomized trials: safflower, sunflower, corn, soybean and other oils lowered LDL cholesterol by 0.23 to 0.42 mmol/l against butter. Ulven et al. (2016; PMID 27737722), Norway, double-blind Neither the participants nor the people assessing them know who received the real treatment until the trial ends., 115 adults: total cholesterol 9 percent and LDL 11 percent lower after 8 weeks. Vafeiadou et al., DIVAS (2015; PMID 26016869), United Kingdom, 195 adults: n-6 polyunsaturated fat in place of saturated fat lowered LDL 13.6 percent. Bjermo et al. (2012; PMID 22492369), Sweden: LDL lower in compliant participants. Ramsden et al. (2016; PMID 27071971): serum cholesterol fell 13.8 percent against 1.0 percent in the Minnesota Coronary Experiment. Hooper et al. (2018; PMID 30488422): total cholesterol 0.33 mmol/L lower on high-quality evidence; LDL showed no clear change in the 2 trials that reported it. LDL is a surrogate, which caps the row at B.
For benefit: Mozaffarian et al. (2010; PMID 20351774), 8 trials and 13,614 participants: coronary events 19 percent lower (RR 0.81, 95% CI 0.70 to 0.95). Hooper et al. (2020; PMID 32827219), cutting saturated fat for at least 2 years: combined cardiovascular events RR 0.83 (0.70 to 0.98), with polyunsaturated fat and carbohydrate replacement not significantly different. Against: Hooper et al. (2018; PMID 30488422), 19 trials of more omega-6 fat: cardiovascular events RR 0.97 (0.81 to 1.15), myocardial infarction 0.88 (0.76 to 1.02). Hamley (2017; PMID 28526025), adequately controlled trials only: major coronary events RR 1.06 (0.86 to 1.31). Ramsden et al. (2013; PMID 23386268), Sydney Diet Heart Study: cardiovascular death 17.2 against 11.0 percent, HR 1.70 (1.03 to 2.80); updated meta-analysis of linoleic acid trials, coronary death HR 1.33 (0.99 to 1.79). Ramsden et al. (2016; PMID 27071971), five trials: coronary death 1.13 (0.83 to 1.54). Schwingshackl and Hoffmann (2014; PMID 24747790), secondary prevention: no significant risk reduction when polyunsaturated fat replaced saturated fat. Randomized trials exist with mixed results that turn on which trials are counted: C.
Every pooled analysis found no difference in deaths from any cause: Hooper et al. (2018; PMID 30488422) RR 1.00; Hamley (2017; PMID 28526025) 1.07 in adequately controlled trials and 1.00 in all trials; Ramsden et al. (2016; PMID 27071971) 1.07; Hooper et al. (2020; PMID 32827219) 0.96 for cutting saturated fat by any replacement. One trial found more deaths on the oil (Sydney Diet Heart Study, 17.6 against 11.8 percent, HR 1.62, 95% CI 1.00 to 2.64; PMID 23386268); the pooled analyses that include it did not reproduce that excess. Tested, no benefit: D on Route 2 Human randomized trials have been run and did not show benefit on the stated outcome. One of the two routes to the lowest letter on EBL's scale..
Lowering LDL and total cholesterol when linoleic-acid oils replace saturated fat (B). Coronary and cardiovascular events (C): mixed results that depend on which trials are pooled. All-cause mortality (D, tested, no benefit). Inflammatory markers: tested as a harm claim, no rise found, no letter.
Why this letter
Why this gradeThe reasoning, and what the grade does not cover.
Grade B on LDL cholesterol. Linoleic-acid oils in place of saturated fat lowered LDL in trials from independent groups in Norway (Ulven et al., 2016; PMID 27737722; LDL 11 percent lower), the United Kingdom (Vafeiadou et al., 2015; PMID 26016869; 13.6 percent lower) and Sweden, Bjermo et al. (2012; PMID 22492369), and in a network meta-analysis of 54 trials (Schwingshackl et al., 2018; PMID 30006369).
WHY NOT ALDL is a surrogate, and a surrogate caps at B; the outcomes LDL stands in for were measured and did not move consistently.
WHY EVENTS SIT AT Cone meta-analysis found 19 percent fewer coronary events (Mozaffarian et al., 2010; PMID 20351774), but the Cochrane review of omega-6 fats found no clear effect on cardiovascular events (Hooper et al., 2018; PMID 30488422; RR 0.97) and the trials judged adequately controlled showed none (Hamley, 2017; PMID 28526025; RR 1.06); C, mixed results, rather than D, because some pooled analyses do show benefit.
WHY MORTALITY IS Devery pooled analysis found no difference in deaths from any cause (PMIDs 30488422, 28526025, 27071971, 32827219).
INFLAMMATION, NO LETTERthe claim that these oils raise inflammation is a harm hypothesis; randomized trials found no significant rise in blood inflammatory markers (Johnson and Fritsche, 2012; PMID 22889633; Su et al., 2017; PMID 28752873), which answers the harm claim but is not a benefit to grade.
WHAT THIS GRADE DOES NOT COVERthe oils eaten on top of an unchanged diet rather than in place of saturated fat; linoleic-acid oils against olive oil or other monounsaturated fat; repeatedly heated frying oil; ultra-processed foods made with these oils; and gamma-linolenic acid supplements, which made up 7 of the 19 trials in the Cochrane omega-6 review.
A grade describes the human evidence for a named use. It is not advice, and it is not a judgment on any individual prescription. How the letters are decided →
Trials report an average. This box says whether any trial on this record looked at who the result applies to, and what it found.
For this record's Grade B · Subgroup tested, effect differedHooper et al. (Cochrane Database of Systematic Reviews A review that searches for every study on a question using a method set in advance, then assesses them together., 2018; PMID 30488422) saw a suggestion of greater protection in participants with lower baseline omega-6 intake. Su et al. (Food and Function, 2017; PMID 28752873) found in subgroup and meta-regression analysis that larger increases in linoleic acid might raise C-reactive protein. Mozaffarian et al. (PLoS Medicine, 2010; PMID 20351774) found longer trials showed greater benefit. A subgroup result shows who the effect appeared in within these trials. It does not change the letter.
Evidence notes: meta-analysis of randomized trials, randomized trial
Endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score. graded: LDL and total cholesterol (surrogate); coronary and cardiovascular events and all-cause mortality on separate rows (surrogate)
Last reviewed: October 2026
The trial that would change this grade.
Positive trials of this shape from independent research groups would move this entry to A.
Why the current trials fall short
The cholesterol fall is settled. Whether it carries through to fewer heart attacks rests on trials more than 45 years old, run in hospitals, nursing homes and clinics. A modern trial that isolates the oil would settle the event and mortality rows in either direction.
ClinicalTrials.gov, the public registry run by the U.S. National Library of Medicine, lists studies that are recruiting volunteers. The link below searches it for Linoleic Acid among studies recruiting now. EBL has no relationship with any listed study and receives no payment for this link.
Search recruiting studies of Linoleic Acid on ClinicalTrials.gov
Each marker links to its entry on the Longevity Lab Panel, which lists every graded record whose trials measured it. Moving a marker is not the same as preventing disease.
- LDL-C: LDL and total cholesterol when linoleic-acid oils replace saturated fat (Grade B for this use)
Dose, form and timing
Measured outcomes: fasting LDL and total cholesterol in feeding trials of weeks to months (PMIDs 30006369, 27737722, 26016869); coronary events and deaths over one to eight years in diet-heart trials (PMIDs 30488422, 20351774, 27071971); blood inflammatory markers in randomized trials (PMIDs 22889633, 28752873).
As studiedDose, form, population and duration for every use.
A grade describes the intervention that was tested. Where the product on the shelf differs from it, this says so.
Safety
Deaths in one trial: in the Sydney Diet Heart Study, men after a coronary event who replaced saturated fat with safflower oil had more deaths from all causes (17.6 against 11.8 percent, HR 1.62, 95% CI 1.00 to 2.64) and from cardiovascular disease (Ramsden et al., 2013; PMID 23386268); pooled analyses including it found no difference in all-cause deaths (PMIDs 30488422, 27071971). Inflammation signals: Su et al. (2017; PMID 28752873) found in subgroup and meta-regression analysis that larger increases in linoleic acid might raise C-reactive protein; adipose tissue genes related to inflammation were upregulated after 7 weeks of safflower oil, while circulating markers fell (Grytten et al., 2025; PMID 40058591); and GlycA rose more after single meals of corn or flaxseed oil than after butter or coconut oil (Limani et al., 2026; PMID 42128091).
Cautions documented in human studies. Each caution on this record, sorted by what it rests on.
- Deaths: in the Sydney Diet Heart Study, men after a coronary event had more deaths on safflower oil (HR 1.62), while pooled analyses found no difference (PMID 23386268 PMID 30488422 PMID 27071971)
- Inflammation signals: subgroup C-reactive protein rises, upregulated adipose inflammation genes and higher GlycA after single meals, while circulating markers fell (PMID 28752873 PMID 40058591 PMID 42128091)
None recorded.
None recorded.
None recorded.
Does not apply: human harm data are listed above.
Grade history
How this letter has changedLatest: No. 396 · October 2026 · First graded.
Seed oils: linoleic-acid vegetable oils in place of saturated fat now has its own record, graded use by use after a full PubMed search in October 2026: LDL and total cholesterol when linoleic-acid oils replace saturated fat (B); Coronary and cardiovascular events when linoleic-acid oils replace saturated fat (C); All-cause mortality when linoleic-acid oils replace saturated fat (D). Lowering LDL and total cholesterol when linoleic-acid oils replace saturated fat (B). Coronary and cardiovascular events (C): mixed results that depend on which trials are pooled. All-cause mortality (D, tested, no benefit). Inflammatory markers: tested as a harm claim, no rise found, no letter. Applied the written grade definitions under the editor's standing instruction of October 2026 (Arnold Sandlow, D.C.).PMID 30488422 PMID 32827219 PMID 20351774 PMID 28526025 PMID 23386268 PMID 27071971 PMID 24747790 PMID 30006369 PMID 12716665 PMID 27737722 PMID 26016869 PMID 22492369
Every change to a letter on this site is dated and published. The full evidence log →
Sources
- Citations
- Every paper cited on this page is matched to its PubMed record on every build.
- Retractions
- None of these papers is retracted or under a journal expression of concern. PubMed is checked again on every build.
- Read against the papers
- October 2026. By a language model (AI-assisted reading), not yet reviewed by a clinician.
- Outside review
- Not yet done. No reviewer outside EBL has checked this record.
What each of these checks can and cannot show: evidence integrity.
The evidence, in full18 papers, each linked to its PubMed record.
Hooper et al. (Cochrane Database of Systematic Reviews, 2018; PMID 30488422): 19 randomized trials, 6,461 participants, one to eight years, higher against lower omega-6 intake (12 trials of linoleic acid, 7 of gamma-linolenic acid supplements); the omega-6 fats usually displaced saturated or monounsaturated fat. All-cause mortality RR 1.00 (95% CI 0.88 to 1.12, low quality); cardiovascular events RR 0.97 (0.81 to 1.15); myocardial infarction RR 0.88 (0.76 to 1.02, low quality); total cholesterol 0.33 mmol/L lower (high quality); LDL -0.04 mmol/L in 2 trials (low quality). Hooper et al. (Cochrane Database of Systematic Reviews, 2020; PMID 32827219): 15 trials, 56,675 participants, at least 2 years of reduced saturated fat; combined cardiovascular events RR 0.83 (0.70 to 0.98), number needed to treat 56 in primary prevention and 53 in secondary prevention; all-cause mortality RR 0.96 (0.90 to 1.03); cardiovascular mortality 0.95 (0.80 to 1.12); replacement with polyunsaturated fat or carbohydrate not significantly different. Mozaffarian et al. (PLoS Medicine, 2010; PMID 20351774): 8 trials, 13,614 participants, 1,042 coronary events; polyunsaturated fat in place of saturated fat, RR 0.81 (0.70 to 0.95), 10 percent lower risk per 5 percent of energy. Hamley (Nutrition Journal, 2017; PMID 28526025): adequately controlled trials only, major coronary events RR 1.06 (0.86 to 1.31), coronary mortality 1.13 (0.91 to 1.40), total mortality 1.07 (0.90 to 1.26); with inadequately controlled trials included, total coronary events 0.80 (0.65 to 0.98). Ramsden et al. (BMJ, 2013; PMID 23386268): recovered data from the Sydney Diet Heart Study, 458 men aged 30 to 59 after a coronary event, safflower oil and safflower margarine in place of saturated fat; all-cause death 17.6 against 11.8 percent (HR 1.62, 1.00 to 2.64), cardiovascular death 17.2 against 11.0 percent (HR 1.70, 1.03 to 2.80). Ramsden et al. (BMJ, 2016; PMID 27071971): recovered data from the Minnesota Coronary Experiment, 9,423 women and men aged 20 to 97, corn oil and corn oil margarine in place of saturated fat; serum cholesterol -13.8 against -1.0 percent; no mortality benefit; in five trials (10,808 participants) coronary death 1.13 (0.83 to 1.54) and all-cause death 1.07 (0.90 to 1.27). Schwingshackl and Hoffmann (BMJ Open, 2014; PMID 24747790): 12 trials, 7,150 people with coronary heart disease; no significant reduction in deaths or events when polyunsaturated fat replaced saturated fat. Schwingshackl et al. (Journal of Lipid Research, 2018; PMID 30006369): network meta-analysis of 54 trials; vegetable oils lowered LDL cholesterol by 0.23 to 0.42 mmol/l against butter. Mensink et al. (American Journal of Clinical Nutrition, 2003; PMID 12716665): 60 controlled trials; the total to HDL cholesterol ratio fell when cis unsaturated fats replaced saturated fats. Ulven et al. (British Journal of Nutrition, 2016; PMID 27737722): 115 adults, 8 weeks, double-blind; total cholesterol -9 and LDL -11 percent, with no difference in C-reactive protein, IL-6, soluble TNF receptor 1 or interferon-gamma. Vafeiadou et al., DIVAS (American Journal of Clinical Nutrition, 2015; PMID 26016869): 195 adults, 16 weeks; n-6 polyunsaturated fat in place of saturated fat lowered LDL cholesterol 13.6 percent; flow-mediated dilatation unchanged. Bjermo et al. (American Journal of Clinical Nutrition, 2012; PMID 22492369): 67 adults with abdominal obesity, 10 weeks; liver fat lower and no signs of inflammation or oxidative stress with n-6 polyunsaturated fat. Drouin-Chartier et al. (American Journal of Clinical Nutrition, 2018; PMID 29381796): 36 men, crossover, 4 weeks per diet; LDL apoB-100 production rate 10.0 percent lower. Johnson and Fritsche (Journal of the Academy of Nutrition and Dietetics, 2012; PMID 22889633): 15 randomized trials in healthy people; no significant rise in C-reactive protein, fibrinogen, plasminogen activator inhibitor 1, cytokines, soluble adhesion molecules or tumor necrosis factor alpha. Su et al. (Food and Function, 2017; PMID 28752873): 30 randomized trials, 1,377 participants; no significant effect on tumor necrosis factor, interleukin-6 or C-reactive protein (16 studies, SMD 0.09, -0.05 to 0.24); subgroup analysis suggested larger increases in linoleic acid might raise C-reactive protein. Grytten et al. (Journal of Lipid Research, 2025; PMID 40058591): 39 adults with abdominal obesity, crossover, 15 to 20 g a day of linoleic acid from safflower oil against fish oil for 7 weeks; no difference between oils in circulating inflammatory markers; adipose tissue inflammatory genes were upregulated after the omega-6 oil. Limani et al. (Clinical Nutrition ESPEN, 2026; PMID 42128091): 18 adults, single high-fat test meals; GlycA rose more after corn and flaxseed oil than after butter or coconut oil, with no consistent pattern across markers.
How EBL searched for the trials (1 search)
The search that was run, what it returned, and what was left out and why, so the absence of evidence can be checked as well as its presence.
("linoleic acid"[tiab] OR "omega-6"[tiab] OR "n-6"[tiab] OR "vegetable oil"[tiab] OR "polyunsaturated fat"[tiab] OR "seed oil*"[tiab]) AND ("saturated fat"[tiab] OR "saturated fatty acids"[tiab]) AND (randomized controlled trial[pt] OR meta-analysis[pt])PubMed watch: does a new study change the grade? (nothing new)
No new paper matching the search behind this grade has been added to PubMed since October 2026.
Last run October 2026. A letter on EBL moves only after a logged review. A new paper never moves a letter by arriving: it is read, the answer is written here, and any change to the letter is published in the evidence log.
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