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. 2018 Jul 18;2018(7):CD003177. doi: 10.1002/14651858.CD003177.pub3

Summary of findings 3.

High versus low omega‐3 fats for modification of CVD risk factors (adiposity and lipids): key outcomes

High versus low omega‐3 fats for modification of CVD risk factors (adiposity and lipids)
Patient or population: adults with or without existing CVD
Setting: participants were living at home for most or all of the duration of their trials. Most studies were carried out in high‐income economies (World Bank 2018), but four trials were carried out in upper‐middle income countries. No studies took place in low‐ or low‐middle income countries.
Intervention: higher omega‐3 intake (LCn3 or ALA) Comparison: lower omega‐3 intake (LCn3 or ALA)
The intervention was dietary supplementation, a provided diet or advice on diet. Supplementation may have been in oil or capsule form or as foodstuffs provided, to be consumed by mouth (excluding enteral and parenteral feeds and enemas). The foodstuffs or supplements must have been: oily fish; fish oils; linseed (flax), canola (rapeseed), perilla, purslane, mustard seed, candlenut, stillingia or walnut as a food, oil, made into a spreading fat or supplementing another food (such as bread or eggs). For ALA sources the product consumed had to have an omega‐3 fat content of at least 10% of the total fat content. Refined eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or alpha‐linolenic acids, or concentrated fish or algal oils, were also accepted.
Outcomes
All in trials of 12 to 72 months' duration 		Anticipated absolute effects* (95% CI) № of participants (studies) Certainty of the evidence (GRADE) Comments
Risk with low omega‐3 Risk with high omega‐3
Measures of adiposity – LCn3 – Weight, kg Mean body weight was 81.2 kg MD 0.01 kg lower (0.84 lower to 0.82 higher) 15812 (12 RCTs) ⊕⊕⊕⊕ Higha LCn3 intake makes little or no difference to body weight.
Measures of adiposity – LCn3 – BMI, kg/m2 Mean BMI was 27.3 kg/m2 MD 0.04 higher (0.16 lower to 0.24 higher) 15234 (14 RCTs) ⊕⊕⊕⊕ Highb LCn3 intake makes little or no difference to BMI.
Serum total cholesterol – LCn3 – TC, mmol/L Mean TC was 5.61 mmol/L MD 0.01 lower (0.05 lower to 0.04 higher) 37281 (28 RCTs) ⊕⊕⊕⊝ Moderatec LCn3 intake probably makes little or no difference to serum total cholesterol.
Serum triglyceride, fasting – LCn3 – TG, mmol/L Mean TG was 1.59 mmol/L MD 0.24 lower (0.32 lower to 0.17 lower) 35534 (24 RCTs) ⊕⊕⊕⊕ Highd Increasing LCn3 intake reduces serum triglyceride.
Serum high density lipoprotein – LCn3 – HDL, mmol/L Mean HDL was 1.32 mmol/L MD 0.02 higher (0 to 0.04 higher) 37237 (27 RCTs) ⊕⊕⊕⊕ Highe Increasing LCn3 intake increases serum HDL.
Serum low density lipoprotein – LCn3 – LDL, mmol/L Mean LDL was 3.27 mmol/L MD 0.01 higher (0.01 lower to 0.03 higher) 35035 (23 RCTs) ⊕⊕⊕⊝ Moderatef LCn3 intake probably makes little or no difference to serum LDL.
Measures of adiposity – ALA – Weight, kg Mean weight was 80.9 kg MD 0.17 higher (0.61 lower to 0.96 higher) 664 (4 RCTs) ⊕⊝⊝⊝ Very lowg The effect of ALA intake on body weight is unclear as the evidence is of very low quality.
Measures of adiposity – ALA – BMI, kg/m2 Mean BMI was 27.4 kg/m2 MD 0.12 higher (0.06 lower to 0.3 higher) 1581 (3 RCTs) ⊕⊕⊝⊝ Lowh ALA intake may make little or no difference to BMI.
Serum total cholesterol – ALA – TC, mmol/L Mean TC was 5.02 mmol/L MD 0.09 lower (0.23 lower to 0.05 higher) 2164 (6 RCTs) ⊕⊕⊝⊝ Lowi ALA intake may make little or no difference to serum total cholesterol (low‐quality/certainty evidence).
Serum Triglyceride, fasting – ALA – TG, mmol/L Mean TG was 1.48 mmol/L MD 0.03 lower (0.11 lower to 0.05 higher) 1776 (6 RCTs) ⊕⊕⊕⊝ Moderatej ALA intake probably makes little or no difference to serum triglycerides (moderate‐quality/certainty evidence).
Serum high density lipoprotein – ALA – HDL, mmol/L Mean HDL was 1.49 mmol/L MD 0.02 lower (0.08 lower to 0.03 higher) 1776 (6 RCTs) ⊕⊕⊕⊝ Moderatek ALA intake probably reduces serum HDL.
Serum low density lipoprotein – ALA – LDL, mmol/L Mean LDL was 2.88 mmol/L MD 0.05 lower (0.15 lower to 0.04 higher) 2201 (7 RCTs) ⊕⊕⊝⊝ Lowl ALA intake may make little or no difference to serum LDL.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). BMI: body mass index; CI: confidence interval; HDL: high‐density lipoprotein; LCn3: long‐chain omega‐3 fatty acids; LDL: low‐density lipoprotein; MD: mean difference; RCT: randomised controlled trial; TC: total cholesterol; TG: triglycerides.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aMeasures of adiposity, weight, LCn3

  • Risk of bias: there was little or no effect in the main analysis or in any sensitivity analysis. Not downgraded.
  • Inconsistency: I2 was < 60%; not downgraded.
  • Indirectness: representative, generalisable adult population including men and women, including healthy participants and participants with previous CVD. However, low‐ and middle‐income countries were underrepresented. Not downgraded.
  • Imprecision: large numbers of participants have taken part in RCTs in long‐term studies with consistent results. 95% confidence intervals exclude important benefits or harms. Not downgraded.
  • Publication bias: funnel plot was not interpretable, no clear small study bias. However, we are aware of several studies whose data could not be included; not downgraded.

bMeasures of adiposity, BMI, LCn3

  • Risk of bias: there was little or no effect in the main analysis or in any sensitivity analysis. Not downgraded.
  • Inconsistency: I2 was < 60%; not downgraded.
  • Indirectness: representative, generalisable adult population including men and women, including healthy participants and participants with previous CVD. However, low‐ and middle‐income countries were underrepresented. Not downgraded.
  • Imprecision: large numbers of participants have taken part in RCTs in long‐term studies with consistent results. 95% confidence intervals exclude important benefits or harms. Not downgraded.
  • Publication bias: funnel plot was not interpretable, no clear small study bias. However, we are aware of several studies whose data could not be included. Not downgraded.

cLipids, serum total cholesterol, LCn3

  • Risk of bias: there was little or no effect in the main analysis or in any sensitivity analysis. Not downgraded.
  • Inconsistency: I2 was < 60%; not downgraded.
  • Indirectness: representative, generalisable adult population including men and women, including healthy participants and participants with previous CVD. However, low‐ and middle‐income countries were not represented. Not downgraded.
  • Imprecision: when we ran fixed‐effect analysis, a statistically significant effect was suggested. The 95% CI included null but excluded important benefits or harms. Downgraded once..
  • Publication bias: funnel plot was not interpretable, no clear small study bias. However, we are aware of several studies whose data could not be included; not downgraded.

dLipids, serum triglycerides, LCn3

  • Risk of bias: there was a statistically significant effect overall and in all sensitivity analyses, including when data were limited to RCTs at low summary risk of bias. Not downgraded.
  • Inconsistency: I2 was < 60%; not downgraded.
  • Indirectness: representative, generalisable adult population including men and women, including healthy participants and participants with previous CVD. However, low‐ and middle‐income countries were not represented. Not downgraded.
  • Imprecision: large numbers of participants have taken part in RCTs in long‐term studies with consistent results. 95% confidence intervals exclude harms. Not downgraded.
  • Publication bias: funnel plot was not interpretable, no clear small study bias. However, we are aware of several studies whose data could not be included; not downgraded.

eLipids, HDL, LCn3

  • Risk of bias: the suggested increase in HDL with increased LCn3 was apparent in all sensitivity analyses. Not downgraded.
  • Inconsistency: I2 was < 60%; not downgraded.
  • Indirectness: representative, generalisable adult population including men and women, including healthy participants and participants with previous CVD. However, low‐ and middle‐income countries were not represented. Not downgraded.
  • Imprecision: large numbers of participants have taken part in RCTs in long‐term studies with consistent results. 95% confidence intervals exclude harms. Not downgraded.
  • Publication bias: funnel plot was not interpretable, no clear small study bias. However, we are aware of several studies whose data could not be included; not downgraded.

fLipids, LDL, LCn3

  • Risk of bias: there was little or no effect in the main analysis or in any sensitivity analysis. Not downgraded.
  • Inconsistency: I2 was < 60%; not downgraded.
  • Indirectness: representative, generalisable adult population including men and women, including healthy participants and participants with previous CVD. However, low‐ and middle‐income countries were not represented. Not downgraded.
  • Imprecision: large numbers of participants have taken part in RCTs in long‐term studies with consistent results. 95% confidence intervals included the null but excluded important benefits or harms. Downgraded once.
  • Publication bias: funnel plot was not interpretable, no clear small study bias. However, we are aware of several studies whose data could not be included; not downgraded.

gMeasures of adiposity, weight, ALA

  • Risk of bias: no included trials were at low summary risk of bias. Downgraded once.
  • Inconsistency: I2 was > 60%, downgraded once.
  • Indirectness: representative, generalisable adult population including men and women, including healthy participants and participants with previous CVD. However, low‐ and middle‐income countries were not represented. Not downgraded.
  • Imprecision: large numbers of participants have taken part in RCTs in long‐term studies with consistent results. 95% confidence intervals include some benefits or harms. Downgraded once.
  • Publication bias: funnel plot was not interpretable, no clear small study bias. However, we are aware of several studies whose data could not be included; not downgraded.

hMeasures of adiposity, BMI, ALA

  • Risk of bias: there was little or no effect in the main analysis or in any sensitivity analysis. Not downgraded.
  • Inconsistency: I2 was > 60%, downgraded once.
  • Indirectness: representative, generalisable adult population including men and women, including healthy participants and participants with previous CVD. However, low‐ and middle‐income countries were not represented. Not downgraded.
  • Imprecision: large numbers of participants have taken part in RCTs in long‐term studies with consistent results. 95% confidence intervals include some benefits and harms. Downgraded once.
  • Publication bias: funnel plot was not interpretable, no clear small study bias. However, we are aware of several studies whose data could not be included; not downgraded.

iLipids, serum total cholesterol, ALA

  • Risk of bias: there was little or no effect in the main analysis or in any sensitivity analysis. Not downgraded.
  • Inconsistency: I2 was > 60%. Downgraded once.
  • Indirectness: representative, generalisable adult population including men and women, including healthy participants and participants with previous CVD. However, low‐ and middle‐income countries were not represented. Not downgraded.
  • Imprecision: when we ran fixed‐effect analysis a statistically significant effect was suggested, but main analysis includes some benefits and harms. Downgraded once.
  • Publication bias: funnel plot was not interpretable, no clear small study bias. However, we are aware of several studies whose data could not be included; not downgraded.

jLipids, serum triglycerides, ALA

  • Risk of bias: there was little or no effect in the main analysis or in any sensitivity analysis. Not downgraded.
  • Inconsistency: I2 was < 60%; not downgraded.
  • Indirectness: representative, generalisable adult population including men and women, including healthy participants and participants with previous CVD. However, low‐ and middle‐income countries were not represented. Not downgraded.
  • Imprecision: large numbers of participants have taken part in RCTs in long‐term studies with consistent results. 95% include benefits and harms. Downgraded once.
  • Publication bias: funnel plot was not interpretable, no clear small study bias. However, we are aware of several studies whose data could not be included; not downgraded.

kLipids, HDL, ALA

  • Risk of bias: there was a statistically significant effect with fixed effects analysis and when data were limited to RCTs at low summary risk of bias, but the main analysis and other sensitivity analyses also suggested reductions om HDL. Not downgraded.
  • Inconsistency: I2 was < 60%; not downgraded.
  • Indirectness: representative, generalisable adult population including men and women, including healthy participants and participants with previous CVD. However, low‐ and middle‐income countries were not represented. Not downgraded.
  • Imprecision: large numbers of participants have taken part in RCTs in long‐term studies with consistent results. 95% CI includes benefits and harms. Downgraded once.
  • Publication bias: funnel plot was not interpretable, no clear small study bias. However, we are aware of several studies whose data could not be included; not downgraded.

lLipids, LDL, ALA

  • Risk of bias: apparent effect altered from slight benefit to slight harm when data were limited to RCTs at low summary risk of bias. Downgraded once.
  • Inconsistency: I2 was < 60%; not downgraded.
  • Indirectness: representative, generalisable adult population including men and women, including healthy participants and participants with previous CVD. However, low‐ and middle‐income countries were not represented. Not downgraded.
  • Imprecision: when we ran fixed‐effect analysis a statistically significant effect was suggested. For main analysis 95% CI included benefits and harms. Downgraded once.
  • Publication bias: funnel plot was not interpretable, no clear small study bias. However, we are aware of several studies whose data could not be included; not downgraded.