Bioavailability of omega-3 fatty acids (FA) depends on their chemical form. Superior bioavailability has been suggested for phospholipid (PL) bound omega-3 FA in krill oil, but identical doses of different chemical forms have not been compared. In a double-blinded crossover trial, we compared the uptake of three EPA+DHA formulations derived from fish oil (re-esterified triacylglycerides [rTAG], ethyl-esters [EE]) and krill oil (mainly PL). Changes of the FA compositions in plasma PL were used as a proxy for bioavailability. Twelve healthy young men (mean age 31 y) were randomized to 1680 mg EPA+DHA given either as rTAG, EE or krill oil. FA levels in plasma PL were analyzed pre-dose and 2, 4, 6, 8, 24, 48, and 72 h after capsule ingestion. Additionally, the proportion of free EPA and DHA in the applied supplements was analyzed. The highest incorporation of EPA+DHA into plasma PL was provoked by krill oil (mean AUC_{0-72 h}: 80.03 ± 34.71%*h), followed by fish oil rTAG (mean AUC_{0-72 h}: 59.78 ± 36.75%*h) and EE (mean AUC_{0-72 h}: 47.53 ± 38.42%*h). Due to high standard deviation values, there were no significant differences for DHA and the sum of EPA+DHA levels between the three treatments. However, a trend (p = 0.057) was observed for the differences in EPA bioavailability. Statistical pair-wise group comparison's revealed a trend (p = 0.086) between rTAG and krill oil. FA analysis of the supplements showed that the krill oil sample contained 22% of the total EPA amount as free EPA and 21% of the total DHA amount as free DHA, while the two fish oil samples did not contain any free FA. Further studies with a larger sample size carried out over a longer period are needed to substantiate our findings and to determine differences in EPA+DHA bioavailability between three common chemical forms of LC n-3 FA (rTAG, EE and krill oil). The unexpected high content of free EPA and DHA in krill oil, which might have a significant influence on the availability of EPA+DHA from krill oil, should be investigated in more depth and taken into consideration in future trials.

In 2016, the first worldwide n3 PUFA status map was published using the Omega-3 Index (O3I) as standard biomarker. The O3I is defined as the percentage of EPA + DHA in red blood cell (RBC) membrane FAs. The purpose of the present study was to update the 2016 map with new data. In order to be included, studies had to report O3I and/or blood EPA + DHA levels in metrics convertible into an estimated O3I, in samples drawn after 1999. To convert the non-RBC-based EPA + DHA metrics into RBC we used newly developed equations. Baseline data from clinical trials and observational studies were acceptable. A literature search identified 328 studies meeting inclusion criteria encompassing 342,864 subjects from 48 countries/regions. Weighted mean country O3I levels were categorized into very low ≤4%, low >4-6%, moderate >6-8%, and desirable >8%. We found that the O3I in most countries was low to very low. Notable differences between the current and 2016 map were 1) USA, Canada, Italy, Turkey, UK, Ireland and Greece (moving from the very low to low category); 2) France, Spain and New Zealand (low to moderate); and 3) Finland and Iceland (moderate to desirable). Countries such as Iran, Egypt, and India exhibited particularly poor O3I levels.

The bioavailability of long-chain omega-3 fatty acids is a critical yet often overlooked factor influencing their efficacy. This review evaluates the bioavailability of EPA/DHA from acute (single-dose) and chronic human studies, focusing on (a) chemical forms such as triacylglycerols (TAG, natural and re-esterified, rTAG), free fatty acids (FFA), and phospholipids (PL) from sources like fish, krill, and microalgae, and (b) delivery methods like microencapsulation and emulsification. Bioavailability for isolated chemically forms followed the order: FFA > PL > rTAG > unmodified TAG > ethyl esters (EE). However, varying oil compositions complicate conclusions about source-specific bioavailability. Significant differences observed in acute bioavailability studies (e.g., faster absorption) often did not translate into long-term impacts in chronic supplementation studies. This raises questions about the clinical relevance of acute findings, especially given that n-3 PUFA supplements are typically consumed long-term. Methodological limitations, such as inappropriate biomarkers, short sampling windows, and inadequate product characterization, hinder the reliability and comparability of studies. The review emphasizes the need for standardized protocols and robust chronic studies to clarify the clinical implications of bioavailability differences. Future research should prioritize biomarkers that reflect sustained n-3 PUFA status to better understand the health benefits of various EPA and DHA formulations.