title: Impact of high dose n-3 polyunsaturated fatty acid treatment on measures of microvascular function and vibration perception in non-alcoholic fatty liver disease: results from the randomised WELCOME trial.
abstract: OBJECTIVE
  The effect of n-3 fatty acid treatment on vibration perception thresholds (VPTs) and cutaneous microvascular reactivity is not known. We tested whether: (1) a 15-18 month treatment with high dose (4 g/day) docosahexaenoic (DHA) plus eicosapentaenoic (EPA) acid improved VPT and microvascular reactivity in patients with non-alcoholic fatty liver disease; and (2) there are associations between VPT, microvascular reactivity and metabolic variables.
  
  
  METHODS
  In the completed single centre, randomised, parallel group, placebo controlled Wessex Evaluation of fatty Liver and Cardiovascular markers in non-alcoholic fatty liver disease with OMacor thErapy (WELCOME) trial, we tested the effect of DHA+EPA on VPT at 125 Hz (big toe) and the cutaneous hyperaemic response (forearm) to arterial occlusion (ratio of maximum to resting blood flux [MF/RF]). Allocation and dispensing was carried out by an independent research pharmacist; all participants and research team members were blinded to group assignment.
  
  
  RESULTS
  In all, 51 and 49 patients were randomised to placebo and DHA+EPA, respectively (mean age 51.4 years). Of these, 32 had type 2 diabetes. Forty-six (placebo) and 47 (DHA+EPA) patients completed the study; there were no important adverse (or unexpected) effects or side effects. In multivariable-adjusted regression models (intention-to-treat analyses), DHA+EPA treatment was associated with an increase in VPT (β coefficient 1.49 [95% CI 0.04, 2.94], p = 0.04). For VPT, the adjusted mean differences (95% CIs) in the placebo and DHA+EPA treatment groups were -0.725 (-1.71, 0.25) and 0.767 (-0.21, 1.75) m/s(2), respectively. With DHA+EPA treatment, there was no change in MF/RF (β coefficient 0.07 [95% CI -0.56, 0.70], p = 0.84), the adjusted mean differences (95% CIs) in the placebo and DHA+EPA treatment groups were -0.549 (-1.03, -0.07) and -0.295 (-0.77, 0.18) respectively. VPT was independently associated with age (β coefficient 0.019 [95% CI 0.010, 0.029], p < 0.0001) and MF/RF (β coefficient -0.074 [95% CI -0.132, -0.016], p = 0.013), but not with diabetes (p = 0.38).
  
  
  CONCLUSIONS
  High dose n-3 fatty acid treatment did not improve measures of microvascular function or vibration perception. Ageing and microvascular reactivity are associated with a measure of peripheral nerve function.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00760513.
  
  
  BACKGROUND
  The study was funded by the National Institute for Health Research UK and Diabetes UK.
authors.affiliation: Human Development and Health Academic Unit, Faculty of Medicine, University Hospital Southampton, MP887, IDS Building, Tremona Road, Southampton, SO166YD, UK.
authors.forename: Keith G
authors.initials: KG
authors.lastname: McCormick
authors.forename: Eleonora
authors.initials: E
authors.lastname: Scorletti
authors.forename: Lokpal
authors.initials: L
authors.lastname: Bhatia
authors.forename: Philip C
authors.initials: PC
authors.lastname: Calder
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Griffin
authors.forename: Geraldine F
authors.initials: GF
authors.lastname: Clough
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Byrne
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D055806:Microvessels / Q000187:drug effects* / Q000503:physiopathology; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000503:physiopathology*; D055698:Touch Perception / Q000187:drug effects*; D014732:Vibration
chemical_list: D015525:Fatty Acids, Omega-3