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Omega-3 fatty acids supplementation may improve inflammation and endothelial activation in HIV-infected adults on stable antiretroviral therapy
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Reported by Jules Levin
11th Workshop on Adverse Drug Reactions and Co-morbidities in HIV
Philadelphia, USA
Oct 26-28 2009
CO Hileman, MD1, M O'Riordan, MS1 and GA McComsey, MD1
1University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH, USA
AUTHOR CONCLUSIONS:
Omega-3 fatty acids may decrease inflammation and improve endothelial dysfunction in HIV-infected patients with good virologic control.
"High sensitivity-CRP (p=0.002), sVCAM-1 (p<0.001) and sICAM-1 (p<0.001) showed a significant decrease after fish oil. The decrease in these markers was independent of changes in total cholesterol, triglycerides, CD4+ cell counts, HIV-1 RNA and ART regimens as these did not change significantly over the study period. Although sTNFR I and II and IL-6 did not change, plasma TNF-a (p<0.001) increased significantly and adiponectin levels (p<0.001) decreased significantly. Conclusion: This pilot study supports our hypothesis that omega-3 fatty acids have potential to decrease inflammation and improve endothelial activation in HIV-infected patients with good virologic control."
LIMITATIONS
This is an uncontrolled, observational study in which the dose, components and adherence to fish oil could not be confirmed. We are in the process of obtaining control samples for this study. Despite this, hs-CRP, sVCAM-1 and sICAM-1 decreased without alternate explanation, results not expected in a population on stable ART with good virologic control.
Unobserved factors may have contributed to the increase in TNF-α and decrease in adiponectin.
Results may be explained by the duration of certain antiretrovirals, as increased TNF-α and reduced secretion of adiponectin have been seen in vivo and in vitro.5-7
ABSTRACT
Objectives/Aim: Omega-3 fatty acids in fish oil decrease coronary artery disease (CAD) risk and cardiovascular mortality. This may be due to anti-inflammatory effect. Inflammation and endothelial dysfunction may play a role in the enhanced cardiovascular risk of HIV infected patients. Our aim was to evaluate changes in markers of inflammation and endothelial activation in virologically-suppressed, HIV-infected adults taking fish oil for 3-6 months.
Methods: We utilized stored plasma from the Case Center for AIDS Research sample repository. Eligibility criteria included: HIV-1 infected, ≥ 18 years, on stable antiretroviral therapy (ART), HIV-1 RNA < 400 copies/ml for study duration, on fish oil for > 3 months, had stored paired plasma samples from before and 3-6 months after initiating fish oil. We excluded subjects with CAD and active infectious or inflammatory conditions. High sensitivity-CRP (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), soluble TNF receptors I and II (sTNFR-I and II), osteoprotegerin, adiponectin, soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) were tested on pre- and post-fish oil samples. The mean of the difference between baseline and follow-up levels were determined for each marker and paired Student's t-tests or Wilcoxon signed rank tests were performed as appropriate.
Results: 47 patients met eligibility criteria. High sensitivity-CRP (p=0.002), sVCAM-1 (p<0.001) and sICAM-1 (p<0.001) showed a significant decrease after fish oil. The decrease in these markers was independent of changes in total cholesterol, triglycerides, CD4+ cell counts, HIV-1 RNA and ART regimens as these did not change significantly over the study period. Although sTNFR I and II and IL-6 did not change, plasma TNF-a (p<0.001) increased significantly and adiponectin levels (p<0.001) decreased significantly.
Conclusion: This pilot study supports our hypothesis that omega-3 fatty acids have potential to decrease inflammation and improve endothelial activation in HIV-infected patients with good virologic control.
Discussion: The most significant limitation of this study is that it is an uncontrolled observational study in which the dose, components and adherence to fish oil could not be confirmed and examined in relation to the magnitude of the outcome. Despite this, hs-CRP, sVCAM-1 and sICAM-1 decreased without alternate explanation, results not expected in a population on stable ART with good virologic control.
However, the same positive effect was not seen for TNF-a or adiponectin. It is possible that despite our careful selection of study participants and samples, there were factors not controlled for that may have contributed to the increase in TNF-a and decrease in adiponectin. One possible explanation is that our entire study population was on ART for the duration of the study. Indeed, in the presence of certain antiretrovirals, increased TNF-a and reduced secretion of adiponectin have been seen in vivo and in vitro.
BACKGROUND
-- Omega-3 fatty acids in fish oil decrease CAD risk and cardiovascular mortality.1,2
-- This may be due to anti-inflammatory effect.3
-- Inflammation and endothelial dysfunction may play a role in the enhanced cardiovascular risk of HIV-infected patients.4
METHODS
We utilized stored plasma from the Case CFAR sample repository.
Inclusion: HIV-1 infected, ≥ 18 years, on ART, HIV-1 RNA < 400 copies/ml for study duration, on fish oil for > 3 months, had stored paired plasma samples from before and 3-6 months after initiating fish oil
Exclusion: CAD, infectious/ inflammatory condition
Inflammatory and endothelial activation markers were tested on pre- and post-fish oil samples. Markers were measured in duplicate and averaged using commercially available enzyme-labeled immunosorbent sandwich assays (Searchlight; Thermo Fisher Scientific, Woburn, MA).
The mean of the difference between baseline and follow-up were determined for each marker. Paired Student's t-tests or Wilcoxon signed rank tests were performed as appropriate.
RESULTS
![](../images/052410/052410-3/image002.gif)
*Mean ± SD
**One person with missing data
***Dose available for 33/47 participants; range
![](../images/052410/052410-3/image004.gif)
*Mean ± SD
**The decreases in hs-CRP, sVCAM-1 and sICAM-1 were similar in participants who took ≥ 2 g vs < 2 g per day
References
1. Rissanen T, et al. Circulation. 2000;102(22):2677-2679.
2. Kromhout D, et al. NEJM. 1985;312(19):1205-1209.
3. Mishra A, et al. Arterioscler Thromb Vasc Biol. 2004;24(9):1621-1627.
4. Kuller LH, et al. PLoS Med. 2008;5(10):e203.
5. Lagathu C, et al. Antivir Ther. 2004;9(6):911-920.
6. Jones SP, et al. Antivir Ther. 2005;10(2):207-213.
7. Lagathu C, et al. Antivir Ther. 2007;12(4):489-500
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