Cardiovascular disease

• 'There is also evidence that replacement of saturated fatty acids by n-6 polyunsaturated fatty acids (without changing total fat intake) decreases the number of cardiovascular events in the population'.

• 'Strong and consistent evidence […] shows that replacing SFA with PUFA reduces the risk of CVD events'.

Coronary Heart Disease

• 'Prospective epidemiological and dietary intervention studies indicate that oily fish consumption or dietary omega-3 long-chain PUFA supplements […] decrease the risk of mortality from coronary heart disease (CHD) and sudden cardiac death.
• 'Under iso-energetic conditions, the most favourable lipoprotein profile to lower atherosclerotic risk is achieved when a mixture of SFA and TFA is replaced by a mixture of oleic acid, linoleic acid and omega-3 long chain PUFA. These effects are dose-dependent'.

• 'Convincing evidence that replacing SFA with PUFA decreases the risk of CHD'.

• Probable evidence for 'primary prevention of CHD through an increase in the intake of PUFA with a simultaneous reduction in SFA intake […] The use of a mixture of n-3 and n-6 fatty acids as a substitute for SFA has proven to be particularly effective in protecting against CHD'.
• Possible evidence for a lack of association  'between primary prevention of CHD and an increase in the intake of PUFA without substitution for SFA'.
• Possible evidence that 'an increased intake of n-6 fatty acids reduces the risk of occurrence of CHD' and that 'an increased intake of ALA reduces CHD mortality'.
• Probable evidence for 'primary prevention of CHD through the intake of long-chain n-3 fatty acids'.  'This applies at least to an intake of up to 250 mg EPA and DHA per day'.

• 'Strong and consistent evidence […] shows that replacing SFA with PUFA reduces the risk of […] coronary mortality. For every 1 percent of energy intake from SFA replaced with PUFA, incidence of CHD is reduced by 2 to 3 percent'.

• 'Growing evidence suggests that dietary n-3 polyunsaturated fatty acids (EPA and DHA) may reduce the risk of many chronic diseases including CHD'.

Blood pressure

• 'n-3 LCPUFA from fish oil and other sources may have a slight beneficial effect on blood pressure, especially at higher intakes (>0.5 g per day)'.
• 'Intervention studies have demonstrated beneficial effects of preformed n-3 LCPUFA on recognised cardiovascular risk factors, such as […] platelet aggregation, and blood pressure'.

• Insufficient evidence on the association between the risk of hypertension and the intake of total PUFA and the ratio of n-6 to n-3 fatty acids.
• 'probable evidence that an increased intake of long-chain n-3 fatty acids lowers risk of hypertension. However, blood pressure […] lowering effects cannot be expected with the amounts of long-chain n-3 fatty acids usually ingested by diet'.
• Probable evidence for no association 'between the substitution of SFA through n-6 fatty acids and risk of hypertension in normotensive persons'.
• 'possible evidence that there is no association between a higher intake of ALA and hypertension risk'.

• Limited evidence (no conclusion) for 'an effect of any modification of the quality of dietary fat on blood pressure'.

Serum lipids

• 'There is a negative (beneficial), dose-dependent relationship between the intake of linoleic acid and blood LDL cholesterol concentrations, while this relationship is positive for HDL cholesterol concentrations. In addition, linoleic acid lowers fasting blood triacylglycerol concentrations, when compared to carbohydrates'.
• 'There is also evidence from dietary intervention studies that decreasing the intakes of products rich in SFA by a replacement of products rich in n-6 PUFA (without changing total fat intake) reduces the number of cardiovascular events'.
• 'Consumption of diets containing trans-monounsaturated fatty acids, like diets containing mixtures of saturated fatty acids, increases blood total and LDL cholesterol concentrations in a dose-dependent manner, compared with consumption of diets containing cis-monounsaturated fatty acids or cis-polyunsaturated fatty acids'.
• 'There is no convincing evidence that any of the conjugated linoleic acids isomers in the diet play a role in prevention or promotion of diet-related diseases'. Therefore, EFSA did not set any DRVs for CLA.
• 'Intervention studies have demonstrated beneficial effects of preformed n-3 LCPUFA on recognised cardiovascular risk factors, such as a reduction of plasma triacylglycerol concentrations…'.

• Long chain n-3 fatty acids.
  • Intake reduces plasma triglyceride concentrations (convincing evidence). However, 'triglyceride-lowering effects cannot be expected with the amounts of long-chain n-3 fatty acids usually ingested by diet […] the amounts required for that can be achieved only through the intake of supplements'.
  • Increased dietary intake has no association with total cholesterol concentration in plasma (probable evidence).
  • Increased intake increases LDL cholesterol  plasma concentration (possible evidence)
  • Intake lacks an association with HDL cholesterol plasma concentration (possible evidence)
  • Insufficient evidence for an association between their intake and ratio of total to HDL cholesterol or the ratio of total to LDL cholesterol.
  • Insufficient evidence  for an effect of the ratio of n-6 to n-3 fatty acids on the plasma lipoproteins and lipids.
• ALA
  • lowers the LDL cholesterol concentration in plasma (convincing evidence).
  • lowers the total cholesterol concentration and has no influence on the HDL cholesterol concentration (probable evidence).
  • insufficient evidence for an influence on the plasma triglyceride concentration, ratio of total to HDL cholesterol, and ratio of LDL to HDL cholesterol.
• N-6 fatty acids
  • Increase in their proportion in the diet lowers plasma concentrations of total and LDL cholesterol and reduces HDL cholesterol (convincing evidence).
  • Increase in their proportion in the diet, at the expense of carbohydrates, lowers the plasma triglyceride concentration (convincing evidence).
  • Their increase (by replacing other fatty acids) has no effect on the plasma triglyceride concentration (probable evidence).
  • Reduce the ratio of total to HDL cholesterol (convincing evidence).
  • Insufficient evidence for an influence on the ratio of LDL to HDL cholesterol.
• CLA
  • Insufficient evidence for effects on plasma concentrations of total, LDL and HDL cholesterol, triglycerides, and ratio of total to LDL and LDL to HDL cholesterol.

• Convincing evidence that ' serum/plasma concentrations of total cholesterol and LDL-cholesterol are reduced when SFA is replaced by […] PUFA'.
• Limited evidence (no conclusion) 'for replacing SFA by […] PUFA in regard to concentrations of serum/plasma HDL-cholesterol'.
• Replacing SFA by PUFA in regard of concentration of serum/plasma total triglyceride levels was 'unlikely' to have any effects.
• Limited evidence (no conclusion) for effects on serum/plasma concentrations of total cholesterol, HDL-cholesterol, and total triglycerides from replacing carbo­hydrates with PUFA.
• Replacing carbohydrates by PUFA in regard of concentration of serum/plasma LDL-cholesterol levels was 'unlikely' to have any effects.
• 'evidence for the hypotriglyceridemic effect of fish oil supplementation compared with cis-MUFA was probable, whereas DHA supplementation did not seem to have a hypotriglyceridemic effect.
• Effect on serum/plasma total cholesterol concentration was evaluated as unlikely when comparing fish oil with other types of PUFA.
• Limited evidence (no conclusion) when comparing fish oil with other types of PUFA 'for its effect on concentrations of LDL- and HDL-cholesterol and total triglycerides'.

• 'Strong and consistent evidence […] shows that replacing SFA with unsaturated fats, especially PUFA, significantly reduces total and LDL cholesterol'.

• Moderate evidence that in controlled feeding trials among adults, for every 1% of energy from SFA that is replaced by 1% of energy from PUFA, LDL and HDL cholesterol is lowered by 1.8 mg/dL and 0.2 mg/dL respectively, while triglycerides decrease by 0.4 mg/dL.
• Moderate evidence that in controlled feeding trials among adults, for every 1% of energy from TFA that is replaced by 1% of energy from PUFA, LDL is lowered by 2.0 mg/dL, HDL cholesterol is increased by 0.5 mg/dL respectively, while triglycerides are lowered by 1.3 mg/dL.

Stroke

• 'probable evidence that intake of PUFA as a whole does not influence risk of stroke'.
• 'possible evidence that the intake of n-6 fatty acids does not influence risk of stroke'.
• Probable evidence for no association between stroke risk and the intake of ALA or long chain n-3 fatty acids.

• 'growing evidence suggests that dietary n-3 polyunsaturated fatty acids (EPA and DHA) may reduce the risk of many chronic diseases including […] stroke'.

Metabolic syndrome

• 'Possible evidence that PUFA affect the risk of alterations in indices related to the metabolic syndrome'.

• Possible evidence for 'an inverse association between PUFA intake and the occurrence of metabolic syndrome'.

• 'Limited studies have shown an inverse relationship between linoleic status and risk factors for type 2 diabetes mellitus including […] metabolic syndrome'.

• 'limited number of human intervention studies in non-diabetic subjects does not provide consistent evidence that fatty acids change insulin sensitivity'.
• 'Epidemiological prospective cohort studies have not found consistent relationships between […] the intake of specific fatty acids […] with the risk to develop type 2 diabetes mellitus'.
• 'n-3 PUFA intake may improve insulin sensitivity […]. Clear dose-response relationships have, however, not been established'.

• 'Possible evidence of a relationship between PUFA intake and reduced risk of diabetes'.

• Insufficient evidence that a higher intake of PUFA or the substitution of SFA with PUFA lowers risk of T2DM
• Possible evidence of no association between T2DM risk and intake of linoleic acid, α-linolenic acid, n-3 long chain fatty acids, and the ratio of n-6 to n-3 fatty acids.

• Unlikely evidence for 'an effect on blood glucose by replacing SFA with […] PUFA'.
• Probable evidence that linoleic acid intake has a 'favourable effect' on the risk of T2DM.
• Suggestive evidence  that the proportion of linoleic acid in plasma phospholipids and cholesteryl esters has a 'favourable effect' on the risk of T2DM.

• 'There is fair evidence that linoleic acid status is inversely associated with risk of type 2 diabetes mellitus. Limited studies have shown an inverse relationship between linoleic status and risk factors for type 2 diabetes mellitus including insulin resistance, metabolic syndrome, inflammation, nerve function/neuropathy, and the liver enzyme, alanine transaminase, as a marker of liver fat'.

• 'Growing evidence suggests that dietary n-3 polyunsaturated fatty acids (EPA and DHA) may reduce the risk of many chronic diseases including […] diabetes'.

• 'For many specific fatty acids, results from prospective cohort studies are still too limited, and sometimes contradictory, to conclude on clear associations between their intakes and the risk of a particular type of cancer'.
• 'Evidence is not sufficient to define a DRV for […] specific fatty acids based on cancer outcome'.

• 'insufficient evidence for establishing any relationship of PUFA consumption with cancer'.

• Suggestive evidence for an inverse association between risk of prostate cancer and intake of α-linolenic acid.

• Probable evidence that 'For most cancers there is […] no association between PUFA intake and the risk of disease'.
• Probable evidence that an 'increased intake of n-6 fatty acids is not associated with the risk of individual cancers'.
• Probable evidence that 'For most of the cancers that were studied […] no association exists between intake of n-3 fatty acids and risk of disease'.
• Probable evidence that 'there is no association between the ratio of n-6 to n-3 fatty acids and risk of cancer'.
• Possible evidence that 'an increasing intake of PUFA may increase the risk of breast cancer'.
• Possible evidence that 'the risk of individual cancers may increase with an increased intake of n-3 fatty acids'.
• Possible evidence that 'an increasing ratio of n-6 to n-3 fatty acids can lead to a decrease in the risk of individual cancers'.

• 'no evidence that, at habitual intakes n-3 PUFA […] and CLA have a discernible impact on energy balance'.

• 'insufficient evidence for relationships of PUFA consumption and body weight and percent adiposity'.

• There is possible evidence for 1) a positive association in women and 2) a lack of an association in men for primary prevention of obesity through a diet with a moderate proportion of PUFA (based on studies with energy adjustment and a biomarker study).
• 'Based on studies without energy adjustment and a biomarker study, there is insufficient evidence for an association between the proportion of n-6 fatty acids in the diet and the primary prevention of obesity'
• Insufficient evidence for the primary prevention of obesity through a diet with an increased proportion of n-3 fatty acids, both with and without energy adjustment.
• ' convincing evidence for a practically insignificant decrease in body fat mass through short-term supplementation with CLA'.
• ' insufficient evidence for the primary prevention of obesity through a long-term diet with an increased proportion of CLA'.

• 'no evidence that the quality of fat has any effect on body weight'.

• 'Fair evidence indicates that 3 to 6 months of CLA supplementation results in a decrease in fat mass and an increase in fat-free mass in healthy adults; however, fair evidence indicates that CLA does not affect body weight'.

• Related to inflammation and immune function, 'There are indications that n-3 LCPUFA from fish oil may have beneficial effects, but results between studies are not consistent', while 'No consistent picture has emerged on the effects of […] CLA and n-6 PUFA on parameters related to inflammation and immune function'.
• 'evidence available is not sufficient to define a DRV for n-3 LCPUFA based on cognitive decline or dementia outcomes'.

• 'Further research is needed to determine whether EPA, DHA, and fish consumption has a protective effect for all-cause dementia'.