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Impact of high dose omega-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

Impact of high dose omega-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
Impact of high dose omega-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
Aims/hypothesis

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 (? 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/s2, respectively. With DHA+EPA treatment, there was no change in MF/RF (? 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 (? coefficient 0.019 [95% CI 0.010, 0.029], p?<?0.0001) and MF/RF (? coefficient ?0.074 [95% CI ?0.132, ?0.016], p?=?0.013), but not with diabetes (p?=?0.38).

Conclusions/interpretation

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.

Trial registration: ClinicalTrials.gov NCT00760513

Funding: The study was funded by the National Institute for Health Research UK and Diabetes UK.
n-3 fatty acid, insulin resistance, microcirculation, non-alcoholic fatty liver disease, omacor/lovaza, sensory nerves, type 2 diabetes, vibration perception threshold
0012-186X
1916-1925
McGormick, Keith G.
95d56eea-74aa-4b48-b950-ab8207e57d08
Scorletti, Eleonora
5d46801d-a34a-453c-a3f5-86ebb6e20195
Bhatia, Lokpal
41232d21-eef2-43a9-a129-994b81ccedaf
Calder, Philip C.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Griffin, Michael .J.
24112494-9774-40cb-91b7-5b4afe3c41b8
Clough, Geraldine F.
9f19639e-a929-4976-ac35-259f9011c494
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
McGormick, Keith G.
95d56eea-74aa-4b48-b950-ab8207e57d08
Scorletti, Eleonora
5d46801d-a34a-453c-a3f5-86ebb6e20195
Bhatia, Lokpal
41232d21-eef2-43a9-a129-994b81ccedaf
Calder, Philip C.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Griffin, Michael .J.
24112494-9774-40cb-91b7-5b4afe3c41b8
Clough, Geraldine F.
9f19639e-a929-4976-ac35-259f9011c494
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c

McGormick, Keith G., Scorletti, Eleonora, Bhatia, Lokpal, Calder, Philip C., Griffin, Michael .J., Clough, Geraldine F. and Byrne, Christopher D. (2015) Impact of high dose omega-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. Diabetologia, 58 (8), 1916-1925. (doi:10.1007/s00125-015-3628-2). (PMID:26021488)

Record type: Article

Abstract

Aims/hypothesis

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 (? 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/s2, respectively. With DHA+EPA treatment, there was no change in MF/RF (? 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 (? coefficient 0.019 [95% CI 0.010, 0.029], p?<?0.0001) and MF/RF (? coefficient ?0.074 [95% CI ?0.132, ?0.016], p?=?0.013), but not with diabetes (p?=?0.38).

Conclusions/interpretation

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.

Trial registration: ClinicalTrials.gov NCT00760513

Funding: The study was funded by the National Institute for Health Research UK and Diabetes UK.

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More information

Accepted/In Press date: 29 April 2015
e-pub ahead of print date: 29 May 2015
Published date: August 2015
Keywords: n-3 fatty acid, insulin resistance, microcirculation, non-alcoholic fatty liver disease, omacor/lovaza, sensory nerves, type 2 diabetes, vibration perception threshold
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 376679
URI: http://eprints.soton.ac.uk/id/eprint/376679
ISSN: 0012-186X
PURE UUID: 223e71eb-9174-4961-9766-2caf958c46fb
ORCID for Michael .J. Griffin: ORCID iD orcid.org/0000-0003-0743-9502
ORCID for Geraldine F. Clough: ORCID iD orcid.org/0000-0002-6226-8964
ORCID for Christopher D. Byrne: ORCID iD orcid.org/0000-0001-6322-7753

Catalogue record

Date deposited: 06 May 2015 13:56
Last modified: 18 Feb 2021 16:53

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Contributors

Author: Eleonora Scorletti
Author: Lokpal Bhatia

University divisions

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