Fish Oil Supplementation Reduces the Number of Circulating Extracellular Vesicles

Written by Chrystal Moulton, Science Writer. Researchers observed a significant decrease in the number of extracellular vesicles in circulation in participants given the fish oil supplement compared to the oily fish meal group (p=0.023) and control (p=0.007).

fish oilVarious nutrients are transported between cells throughout the body via extracellular vesicles1. These vesicles play a vital role in tissue repair, cell communication, and various physiological processes2,3. Previous studies have shown that supplementation with omega-3 fatty acids could reduce the amount of extracellular vesicles in circulation4,5, including specific subtypes6. Little is known however, about the effect of dietary omega-3 consumption on the number of circulating extracellular vesicles nor the effect of EPA and DHA on circulating extracellular vesicles. In the current trial, researchers investigated the effect of dietary omega-3 fatty acid versus fish oil supplementation on circulating extracellular vesicles7.

This study was designed as a randomized placebo-controlled trial in which participants were randomly assigned to receive either:

  1. 2g/d of omega-3 in capsule form daily and 2 whitefish meals per week (control meal)
  2. Olive oil capsules (control) daily and 2 oily fish meals [1 salmon meal and 1 mackerel meal equivalent to 2.2g/d of omega-3]
  3. Olive oil capsules (control) daily and 2 whitefish meals per week (control meal)

All meals were delivered to participants twice a week. Three-day food records were collected 3 days prior to start of trial and the last 3 days of the trial. Study duration was 12 weeks and participants were followed-up at baseline and at the end of intervention after screening. Eligible participants were over the age of 40 years old with a relative risk of 1.5 for CVD based on Framingham Risk Score. Participants with a history of stroke, autoimmune disease, neurological disease, type 2 diabetes, HIV, immune disorders, alcohol misuse, taking medications and/or dietary supplements (such as fish oil once/week), pregnant or breastfeeding were excluded from this trial. Blood samples were collected from participants at baseline and end of trial. Concentration of total extracellular vesicles and vesicle subtypes were measured as well as fatty acid composition of red blood cells and extracellular vesicles. Thrombin generation and clot formation was also assessed in both platelet free plasma and vesicle depleted plasma. Plasma lipid profile was also measured in all volunteers.

Forty-two participants completed the trial [Fish oil supplement group (n=15), Oily Fish meal group (n=14), control (n=13)]. The average age of participants was 55 ±2years old with no significant differences between groups at baseline. Researchers observed no significant difference in lipid profile or clot formation between groups. EPA, DHA, and total PUFAs increased significantly in red blood cell and extracellular vesicles for both the fish oil and oily fish meal groups compared to placebo (p<0.05). Omega-6 in red blood cells decreased significantly in both groups also compared to placebo. Researchers also saw a significant decrease in the number of extracellular vesicles in circulation in participants given the fish oil supplement compared to the oily fish meal group (p=0.023) and control (p=0.007). Furthermore, participants supplemented with the fish oil showed a significantly lower concentration of thrombin compared to oily fish meal (p<0.001) and control (p=0.001) groups. There was also a significant decrease in overall concentration of thrombin (AUC) in the fish oil supplement group compared to the oily fish meal and control groups (p<0.05). Additionally, data showed the proportion EPA in extracellular vesicles and red blood cells was significantly associated with the number of extracellular vesicles in circulation and thrombin generation.

Overall, fish oil supplementation was more effective in lowering thrombin generation and circulating extracellular vesicles, which researchers found was strongly associated with the 1g/d of EPA present in the fish oil supplement. Additional studies will be needed to verify these findings.

Source: Sharman, Amal, Ruihan Zhou, Jamie Pugh, Graeme Close, Helena L. Fisk, Philip C. Calder, and Parveen Yaqoob. “High-dose fish oil supplements are more effective than oily fish in altering the number and function of extracellular vesicles in healthy human subjects: a randomised, double-blind, placebo-controlled, parallel trial.” British Journal of Nutrition (2025): 1-11.

© The Author(s), 2025. Published by Cambridge University Press on behalf of The Nutrition Society. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creative
commons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.

Click here to read the full text study.

Posted April 29, 2025.

Chrystal Moulton BA, PMP, is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Indianapolis, IN.

References:

  1. Badimon L, Padro T, Arderiu G, Vilahur G, Borrell-Pages M, Suades R. Extracellular vesicles in atherothrombosis: From biomarkers and precision medicine to therapeutic targets. Immunological reviews. Nov 2022;312(1):6-19. doi:10.1111/imr.13127
  2. Yáñez-Mó M, Siljander PR, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066. doi:10.3402/jev.v4.27066
  3. Villa F, Quarto R, Tasso R. Extracellular Vesicles as Natural, Safe and Efficient Drug Delivery Systems. Pharmaceutics. Oct 28 2019;11(11)doi:10.3390/pharmaceutics11110557
  4. Wu SY, Mayneris-Perxachs J, Lovegrove JA, Todd S, Yaqoob P. Fish-oil supplementation alters numbers of circulating endothelial progenitor cells and microparticles independently of eNOS genotype. Am J Clin Nutr. Nov 2014;100(5):1232-43. doi:10.3945/ajcn.114.088880
  5. Del Turco S, Basta G, Lazzerini G, et al. Effect of the administration of n-3 polyunsaturated fatty acids on circulating levels of microparticles in patients with a previous myocardial infarction. Haematologica. Jun 2008;93(6):892-9. doi:10.3324/haematol.11845
  6. Bozbas E, Zhou R, Soyama S, et al. Dietary n-3 polyunsaturated fatty acids alter the number, fatty acid profile and coagulatory activity of circulating and platelet-derived extracellular vesicles: a randomized, controlled crossover trial. Am J Clin Nutr. May 2024;119(5):1175-1186. doi:10.1016/j.ajcnut.2024.03.008
  7. Sharman A, Zhou R, Pugh J, et al. High-dose fish oil supplements are more effective than oily fish in altering the number and function of extracellular vesicles in healthy human subjects: a randomised, double-blind, placebo-controlled, parallel trial. Br J Nutr. Mar 21 2025:1-11. doi:10.1017/s0007114525000625

 

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