Caldwell 2011

Methods	RCT, parallel, (n‐3 EPA + DHA vs n‐6 LA), 12 months Summary risk of bias: low
Participants	Participants with non‐cirrhotic NASH (non‐alcoholic steatohepatitis) N: 20 intervention, 21 control (analysed 17 intervention, 17 control) Level of risk for CVD: moderate Men: 35.3% intervention, 41.2% control Mean age in years (SD): 46.4 (12.1) intervention, 47.2 (12) control Age range: 25‐72 years Smokers: not reported Hypertension: not reported Medications taken by at least 50% of those in the control group: not reported Medications taken by 20%‐49% of those in the control group: not reported Medications taken by some, but less than 20% of the control group: not reported Location: USA Ethnicity: intervention, 100% white, control 94.% white, 5.9% other
Interventions	Type: supplement (capsule) Comparison: EPA + DHA vs omega 6 Intervention: 3 × 1 g fish oil capsules/d (Nordic Natural) for a total 2.1 g/d n‐3, each capsule contained 70% of n‐3 (1050 mg EPA, 750 mg DHA + 300 mg other n‐3). Dose: 1.8 g/d EPA + DHA Control: 3 × 1 g identical placebo (soybean) capsules per day containing 8% fish oils Both groups had dietary counselling on caloric intake and physical activity Compliance: unclear (measured n‐6‐n‐3 ratio due to its link to hepatic lipid composition) Length of intervention: 12 months
Outcomes	Main study outcome: NASH activity score Dropouts: 3 intervention, 3 control Available outcomes: lipids (TG too unbalanced at baseline to use), measures of adiposity (weight, BMI, visceral fat – all unbalanced at baseline so not used), fasting glucose, insulin, HOMA‐IR, QUICKI (also NASH progression, hepatic fat, ALT, VO2 max, activity level, markers of cell injury, adiponectin not used) Response to contact: yes, change data supplied for BMI and body weight, confirmed no deaths, cardiovascular events, diabetes, depression, breast cancer or IBD diagnoses
Notes	Data on; BMI, weight, visceral fat, TG and glucose were not used as they were different between groups at baseline. Study funding: study was supported by NIH NCCAM Grant 5R21AT2901–2 and 5 M01 RR00847. Study medication and identical appearing placebo was provided at no charge by Nordic Natural. RBC phospholipid profile was performed by Metametrix (www.metametrix.com). M30, M65, adiponectin, and IGFBP‐1 electro chemiluminescence assays were performed by Wellstat Diagnostics (www.wellstatdiagnostics.com).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomised to n‐3 or placebo using a stratified block 1:1 randomisation scheme. An independent biostatistician generated the randomisation list which was confidentially forwarded to the Investigational pharmacy
Allocation concealment (selection bias)	Low risk	As above
Blinding of participants and personnel (performance bias) All outcomes	Low risk	All staff and subjects were blinded to therapy assignment throughout the study period. Both capsules were identical. However no information provided on capsules taste or smell
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinded for main outcome
Incomplete outcome data (attrition bias) All outcomes	Low risk	15% dropouts explained and equal in both groups
Selective reporting (reporting bias)	Low risk	The trial was prospectively registered
Attention	Low risk	Both groups had the same attention
Compliance	Unclear risk	No details on compliance measurement
Other bias	Low risk	None noted