Pharmacokinetics of omega-3 fatty acids in patients with severe sepsis compared with healthy volunteers: A prospective cohort study
Clinical Nutrition, DOI: https://doi.org/10.1016/j.clnu.2019.03.040
Radhika Parikh a, Jason H.T. Bates a, Matthew E. Poynter a, Benjamin T. Suratt a, Polly E. Parsons a, C. Lawrence Kien a, Daren K. Heyland b, Karen I. Crain a, Julie Martin c, Jayanthi Garudathria, Renee D. Stapleton a,∗
- Sepsis mortality cut in half with Omega-3 – RCT Sept 2017
- Omega-3 reduced cost of Sepsis by 2900 dollars per patient (12 RCT) – April 2018
- Sepsis: 4 fewer days in ICU if add Omega-3 – meta-analysis of 12 RCT – June 2017
- Overview: Omega-3 many benefits include helping vitamin D
- Sepsis is both prevented and treated by Vitamin D - many studies 8 fewer ICU days with Vitamin D – RCT
- Wonder how many fewer days if had used BOTH Vitamin D and Omega-3
Omega-3 and Inflammation (items in both categories)
- Opioid addiction reduced by Omega-3 (gut inflammation in mice) – Aug 2019
- Treat wounds, stop inflammation with nanoemulsion textile of Omega-3 and Resveratrol - Sept 2019
- Inflammation is reduced by each of the following: Vitamin D, Omega-3, Diet
- Sepsis reduced the Omega-3 response and half life – April 2019
- Pollutants increase Respiratory problems, Vitamin D, Omega-3, etc. decrease them – May 2018
- Severe acute pancreatitis treated in 11 ways by Omega-3 in just 7 days – RCT April 2018
- Omega-3 treats animal inflammation better than human (those studies use higher doses and different ratios than for humans) - March 2018
- Omega-3 helps muscles and reduces inflammation, lipids, and insulin – Nov 2015
- Omega-3 improves gut bacteria, reduces inflammation and depression – Dec 2017
- Can burn pain be relieved by 4 g of Omega-3 and 2,000 IU of vitamin D – RCT due 2021
- 2.7 fewer days in hospital after surgery if had taken Omega-3 (19 RCT) – meta-analysis – June 2017
- Sepsis: 4 fewer days in ICU if add Omega-3 – meta-analysis of 12 RCT – June 2017
- Omega-3 reduces many psychiatric disorders – 2 reviews 2016
- Depression due to inflammation reduced by Omega-3 (children and pregnant) – Nov 2015
- Omega-7 - in addition to Omega-3
- Inflammation reduction through diet: Omega-3 etc. Feb 2014
- Traumatic brain injury treated by Vitamin D Progesterone Omega-3 and glutamine – May 2013
- Omega-3 reduced vitamin D3 inflammation for obese – RCT Jan 2013
 Download the PDF from Sci-Hub via VitaminDWiki
Half-Life
Background
Pharmacokinetics (PK) of pharmaceuticals and pharmaconutrients are poorly understood in critically ill patients, and dosing is often based on healthy subject data. This might be particularly problematic with enteral medications due to metabolic abnormalities and impaired gastrointestinal tract absorption common in critically ill patients. Utilizing enteral fish oil, this study was undertaken to better understand and define PK of enteral omega-3 fatty acids (eicospentaenoic acid [EPA] and docosahexaenoic acid [DHA]) in critically ill patients with severe sepsis.
Materials and methods
Healthy volunteers (n = 15) and mechanically ventilated (MV) adults with severe sepsis (n = 10) were recruited and received 9.75 g EPA and 6.75 g DHA daily in two divided enteral doses of fish oil for 7 days. Volunteers continued their normal diet without other sources of fish oil, and sepsis patients received standard enteral feeding. Blood was collected at frequent intervals during the 14-day study period. Peripheral blood mononuclear cells (PMBCs) and neutrophils were isolated and analyzed for membrane fatty acid (FA) content. Mixed linear models and t-tests were used to analyze changes in FA levels over time and FA levels at individual time points, respectively. PK parameters were obtained based on single compartment models of EPA and DHA kinetics.
Results
Healthy volunteers were 41.1 ± 10.3 years; 67% were women. In patients with severe sepsis (55.6 ± 13.4 years, 50% women), acute physiologic and chronic health evaluation (APACHE) II score was 27.2 ± 8.8 at ICU admission and median MV duration was 10.5 days. Serum EPA and DHA were significantly lower in sepsis vs. healthy subjects over time. PBMC EPA concentrations were generally not different between groups over time, while PBMC DHA was higher in sepsis patients. Neutrophil EPA and DHA concentrations were similar between groups. The half-life of EPA in serum and neutrophils was significantly shorter in sepsis patients, whereas other half-life parameters did not vary significantly between healthy volunteers and sepsis patients.
Conclusions
While incorporation of n-3 FAs into PBMC and neutrophil membranes was relatively similar between healthy volunteers and sepsis patients receiving identical high doses of fish oil for one week, serum EPA and DHA were significantly lower in sepsis patients. These findings imply that serum concentrations and EPA and DHA may not be the dominant driver of leukocyte membrane incorporation of EPA and DHA. Furthermore, lower serum EPA and DHA concentrations suggest that either these n-3 FAs were being metabolized rapidly in sepsis patients or that absorption of enteral medications and pharmaconutrients, including fish oil, may be impaired in sepsis patients. If enteral absorption is impaired, doses of enteral medications administered to critically ill patients may be suboptimal.