() Randomised, 3 crossover, single blind Determine whether the consumption of milk naturally or synthetically enriched with CLA alters blood lipids, liver function, C reactive protein, tumour necrosis factor alpha, body weight and body composition in moderately overweight, borderline hyperlipidaemia participants. Initial: 18 final: 15. Reason for loss: Personal reasons (n = 2) and pregnancy (n = 1) 46.6 years+/- 2.0, 44% female, moderately overweight, borderline Natural CLA: 4.2% of milk fats, iTFA: 4.2% and untreated control. 3 x 8 week dietary periods separated by 4 week wash out period. Participants consumed 1000mls/day of milk naturally enriched with CLA, milk synthetically enriched with CLA or untreated milk in addition to their usual diet (uncontrolled). Diet arm which included synthetic CLA did not meet review inclusion criteria and was therefore excluded from the analysis. Dose of CLA in natural products achieved via and therefore in the study, is limited by ability to naturally increase levels via animal feed. () Randomised, single multiple crossover trial Study the effect of high doses of CLA on lipoprotein levels in human RCTs Initial: 63 final: 61. Reason for loss: Illness and personal reasons. Both unrelated to the trial. 30.9 +/- 13.7, years, 59% female, healthy High oleic acid, CLA, and vegetable oil Total TFA intake was 1.6% higher in CLA diet compared to iTFA. were identical other than the 7% of total energy as CLA, industrial TFA or oleic acid. iTFA used as a positive control. CLA arm did not meet inclusion criteria of the current review and these results were excluded from the analysis. Men were more sensitive to the effects of TFA than women. No washout period between diets. CLA: conjugated linoleic acid, HDL: high density lipoprotein, iTFA: industrial trans fatty acids, LDL: low density lipoprotein, MUFA: monounsaturated fatty acids, rTFA: ruminant trans fatty acids, TFA: Trans fatty acids
Appendix 2 Figure 1. Assessment of publication bias for studies reporting total cholesterol outcomes Figure 2. Assessment of publication bias for studies reporting LDL cholesterol outcomes Figure 3. Assessment of publication bias for studies reporting HDL cholesterol outcomes Appendix 3 Table 1. Summary of GRADE findings Trans fatty acids and change in total, LDL and HDL blood cholesterol Patient or population: Humans Settings: Randomised controlled trials Intervention: One per cent increase in TFA intake in exchange for cis-MUFA (expressed as a percentage of energy intake) Comparison: Control Outcomes Illustrative comparative risks* (95% CI) Relative effect (95% CI) No of Participants (studies) Quality of the evidence (GRADE) Comments Assumed risk Corresponding risk Plasma blood lipids One per cent increase in TFA intake as a percentage of energy intake Total cholesterol Follow-up: 3-12 weeks The mean cholesterol in the intervention groups was 0.02 higher (0.02 lower to 0.07 higher) 411 (10 studies) ⊕⊕⊕⊝ moderate1,2 LDL cholesterol Follow-up: 3-32 weeks The mean LDL cholesterol in the intervention groups was 0.04 higher (0.03 to 0.06 higher) 2218 (9 studies and 1 existing ⊕⊕⊕⊕ high2,3 HDL cholesterol Follow-up: 3-32 weeks The mean HDL cholesterol in the intervention groups was 0.01 lower (0.02 lower to 0 higher) 2180 (8 studies and 1 existing ⊕⊕⊕⊕ high2,3 *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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). CI: Confidence interval; GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the