NAFLD patients who raised their red blood cell (RBC) docosahexaenoic acid (DHA) level by more than 2%, showed significant improvements in liver metabolism and hepatic insulin sensitivity, reported the multi-centre research team from the Universities of Oxford, Southampton and Surrey.
The increase in RBC DHA content, induced by 15-18 month supplementation of high-dose (4 grams per day (g/d)) long-chain omega-3 fatty acids (FA), improved FA oxidation and insulin sensitivity in the liver. Supplementation also reduced the amount of new fat deposited in the liver – a process called de novo lipogenesis (DNL). Existing liver fat content was also reduced by 26%, although this was not statistically significant.
“The findings from our pilot study indicate that individuals who achieved a change in erythrocyte DHA enrichment greater than or equal to2% show favourable changes in hepatic FA metabolism and insulin sensitivity, which may contribute to decreasing hepatic fat content,” wrote co-author Professor Leanne Hodson of Oxford University.
Another important finding was that increasing RBC DHA content by greater than 2% reduced hepatic, but not whole-body (peripheral) insulin sensitivity. Previous researchers had reported mixed results on the effects of short-term omega-3 FA on whole-body insulin sensitivity.
This investigation was a pre-specified sub-study of the Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy (WELCOME) trial – a double-blinded randomised controlled trial (RCT).
Sixteen NAFLD patients were randomised to receive either 4 g/d of omega-3 FA (Omacor formulation, containing DHA 1.84 g/d of and EPA 1.56 g/d) or 4 g/d olive oil placebo over 15-18 months.
RBC DHA content was measured at baseline and at the end of the study. Assessment was made of various parameters of NAFLD including hepatic and whole-body insulin sensitivity, existing liver fat, DNL, FA oxidation and triglycerides. Results were compared between patients displaying RBC DHA enrichments of either >2% or <2%.
Unexpectedly, one of the placebo group displayed an RBC DHA increase of over 2%. The researchers suggested this might have been due to possible increased consumption of oily fish during the trial period. However, this raises the question of why trial participants were not given guidelines on avoiding dietary changes that might confound the trial outcome, or least notifying the researchers of any substantial intake of dietary omega-3.
In this study, the prime outcome was to examine the effect of raising RBC DHA on markers of NAFLD. No attempt was made to assess if EPA had an influence on these parameters. Thus, individual beneficial effects on NAFLD of EPA and DHA could not be isolated.
However, a previous meta-analysis covered by NutraIngredients earlier this year concluded that DHA is more effective than EPA; although outcomes in the range of studies included in the meta-analysis placed more emphasis on liver enzyme changes rather than insulin sensitivity and DNL reduction.
The researchers suggested that measuring the effect of a DHA-only oil would be an appropriate subject of further research.
“It would be of interest to study the effect of a DHA treatment only on hepatic metabolism and insulin sensitivity,” they concluded.
Source: European Journal of Clinical Nutrition
Volume 71, issue 8, pp 973-979. DOI: 10.1038/ejcn.2017.9
“Docosahexaenoic acid enrichment in NAFLD is associated with improvements in hepatic metabolism and hepatic insulin sensitivity: a pilot study”
Authors: L. Hodson, L. Bhatia et al.