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/hypothesisThe 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.MethodsIn 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.ResultsIn 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/interpretationHigh 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 NCT00760513Funding: The study was funded by the National Institute for Health Research UK and Diabetes UK

Hydrogen Bonding in Phosphonate Cavitands: Investigation of Host-Guest Complexes with Ammonium Salts

The H-bonding in alkylammonium complexes of phosphonate cavitands were studied by mass spectrometric methods and theoretical calculations. The alkylammonium ions included primary, secondary, and tertiary methyl- and ethylammonium ions. Their complexation with mono-, tetra-, and two di-phosphonate cavitands, which differ according to the number and position of H-bond acceptor P = O groups, was evaluated by using different competition experiments, energy-resolved CID, gas-phase H/D-exchange, and ligand-exchange reactions, together with ab initio theoretical optimization of the complexes. The phosphonate cavitands with two or more adjacent P = O groups were found to be selective towards secondary alkylammonium ions, due to simultaneous formation of two stable hydrogen bonds. In the ion-molecule reactions (both H/D- and ligand-exchange), the formation of two stable hydrogen bonds was observed either to slow down the reaction or to completely prevent it. This was, however, limited to situations where two hydrogen bonds are formed between the H-bond donor sites of the alkyl ammonium ion and the vicinal H-bond acceptor sites of the cavitand