To explore the safety and efficacy of fish oil to modulate parameters of inflammation and immunosenescence in HIV-infected older adults.
Design:
This study uses a randomized, controlled, double-blind clinical trial.
Setting:
The study was conducted in an outpatient HIV/AIDS clinic in a large urban Midwestern city in the United States.
Subjects:
A total of 37 clinically stable HIV-infected adults between the ages of 40 and 70 years of age participated.
Interventions:
Fish oil 1.6 g/day was administered for 12 weeks or placebo.
Outcome measures:
Inflammatory cytokine production, surface markers of immunosenescence, and adverse events were measured.
Results:
After 12 weeks of supplementation, there were no significant differences between the treatment and control groups on any measures of inflammation or immunosenescence in both CD4+ and CD8+ T lymphocytes. More participants in the treatment group reported adverse gastrointestinal events compared with the control group.
Conclusions:
A 12-week supplementation regimen of 1.6 g/day of fish oil did not favorably modulate parameters of inflammation or immune senescence in HIV-infected adults. Future studies should test agents that directly target mechanisms that underlie HIV-related inflammation to determine whether reducing inflammation can reverse immunosenescence.
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References
1.
GnoniML, FriedstromS, BlattS, et al.Sources for inflammation and accelerated aging in well controlled HIV patients on antiretroviral therapy. J Infect Dis Ther, 2015; 3:239.
ShiveCL, ClagettB, McCauslandMR, et al.Inflammation perturbs the IL-7 axis, promoting senescence and exhaustion that broadly characterize immune failure in treated HIV infection. J Acquir Immune Defic Syndr, 2016; 71:483–492.
4.
TanaskovicS, FernandezS, PriceP, FrenchMA. Interleukin-7 signalling defects in naive CD4+ T cells of HIV patients with CD4+ T-cell deficiency on antiretroviral therapy are associated with T-cell activation and senescence. AIDS, 2014; 28:821–830.
5.
ChenL, FliesDB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol, 2013; 13:227–242.
6.
AppayV, SauceD. Immune activation and inflammation in HIV-1 infection: Causes and consequences. J Pathol, 2008; 214:231–241.
7.
DeeksSG. HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med, 2011; 62:141–155.
8.
BrenchleyJM, KarandakarNJ, BettsMR, et al.Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells. Blood, 2003; 101:2711–2720.
9.
NixonDE, LandayAL. Biomarkers of immune dysfunction in HIV. Curr Opin HIV AIDS, 2010; 5:498–503.
10.
BrenchleyJM, PriceDA, SchackerTW, et al.Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med, 2006; 12:1365–1371.
11.
EnioutinaEY, VisicDM, DaynesRA. Enhancement of common mucosal immunity in aged mice following their supplementation with various anti-oxidants. Vaccine, 2000; 18:2381–2393.
12.
ZhangK, MaX, HeW, et al.Extracts of Cistanche deserticola can antagonize immunosenescence and extend life span in senescence-accelerated mouse prone 8 (SAM-P8) mice. Evid Based Complement Altern Med, 2014; 2014:601383.
13.
CalderPC. Mechanisms of action of (n-3) fatty acids. J Nutr, 2012; 142:592S–599S.
14.
CalderPC. Functional roles of fatty acids and their effects on human health. J Parenter Enteral Nutr, 2015; 39:18S–32S.
15.
CalderPC. Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance. Biochim Biophys Acta, 2015; 1851:469–484.
16.
KremerJM. n-3 Fatty acid supplements in rheumatoid arthritis. Am J Clin Nutr, 2000; 71:349s–351s.
17.
AdamO, BeringerC, KlessT, et al.Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Rheumatol Int, 2008; 23:27–36.
18.
MickleboroughTD, LindleyMR, IonescuAA, FlyAD. Protective effect of fish oil supplementation on exercise-induced bronchoconstriction in asthma. Chest, 2006; 129:39–49.
19.
WangX, LiW, LiN, LiJ. ω-3 Fatty acids-supplemented parenteral decreases hyperinflammatory response and attenuates systemic disease sequelae in severe acute pancreatitis: A randomized and controlled study. J Parenter Enteral Nutr, 2008; 32:236–241.
20.
BelluzziA, BrignolaC, CampieriM, et al.Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. N Engl J Med, 1996; 334:1557–1560.
21.
LiK, HuangT, ZhengJ, et al.Effect of marine-derived n-3 polyunsaturated fatty acids on C-reactive protein, interleukin 6 and tumor necrosis factor α: A meta-analysis. PLoS One, 2014; 9:e88103.
22.
LichtensteinAH, AppelLJ, BrandsM, et al.Summary of American Heart Association diet and lifestyle recommendations revision. Arterioscler Thromb Vasc Biol, 2006; 26:2186–2191.
23.
HellersteinMK, WuK, McGrathM, et al.Effects of dietary n-3 fatty acid supplementation in men with weight loss associated with the acquired immune deficiency syndrome: Relation to indices of cytokine production. J Acquir Immune Defic Syndr, 1996; 11:258–270.
24.
BellSJ, ChavaliS, BistrianBR, et al.Dietary fish oil and cytokine and eicosanoid production during human immunodeficiency virus infection. J Parenter Enteral Nutr, 1996; 20:43–49.
25.
DeutschL. Evaluation of the effects of Neptune krill oil on chronic inflammation and arthritic symptoms. J Am Coll Nutr, 2007; 26:39–48.
26.
MarsagliaG, AnanthanarayananK, PaulN. Random Number Generator Package–‘Super Duper’. Quebec, Canada: McGill University in Montreal, 1973.
27.
BuneaR, El FarrahK, DeutschL. Evaluation of the effects of Neptune krill oil on the clinical course of hyperlipidemia. Altern Med Rev, 2004; 9:420–428.
28.
SwansonB, ShaBE, KeithleyJK, et al.Policosanol for managing HIV-related dyslipidemia in a medically-underserved population: A randomized, controlled clinical trial. Altern Ther Health Med, 2011; 17:30–35.
29.
StarkKD. The percentage of n-3 highly unsaturated fatty acids in total HUFA as a biomarker for omega-3 fatty acid status in the tissues. Lipids, 2008; 43:45–53.
30.
ProudmanSM, JamesMJ, SpargoLD, et al.Fish oil in recent onset rheumatoid arthritis: A randomised, double-blind controlled trial within algorithm-based drug use. Ann Rheum Dis, 2015; 74:89–95.
31.
ArriensC, HynanLS, LermanRH, et al.Placebo-controlled randomized clinical trial of fish oil's impact on fatigue, quality of life, and disease activity in systemic lupus erythematosus. Nutr J, 2015; 14:1–11.
32.
MorrowJD, FreiB, LongmireAW, et al.Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers—smoking as a cause of oxidative damage. N Engl J Med, 1995; 332:1198–1203.
33.
PawloskyRJ, HibbelnJR, SalemN. Compartmental analyses of plasma n-3 essential fatty acids among male and female smokers and nonsmokers. J Lipid Res, 2007; 48:935–943.
34.
AlmanzarG, SchwaigerS, JeneweinB, et al.Long-term cytomegalovirus infection leads to significant changes in the composition of the CD8+ T-cell repertoire, which may be the basis for an imbalance in the cytokine production profile in elderly persons. J Virol, 2005; 79:3675–3683.
35.
HadrupSR, StrindhallJ, KøllgaardT, et al.Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly. J Immunol, 2006; 176:2645–2653.
36.
HuntPW, MartinJN, SinclairE, et al.Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+ T cell recovery on antiretroviral therapy. J Infect Dis, 2011; 203:1474–1483.
37.
LenkeiR, AnderssonB. High correlations of anti-CMV titers with lymphocyte activation status and CD57 antibody-binding capacity as estimated with three-color, quantitative flow cytometry in blood donors. Clin Immunol Immunopathol, 1995; 77:131–138.
38.
NapolitanoLA, SchmidtD, GotwayMB, et al.Growth hormone enhances thymic function in HIV-1-infected adults. J Clin Invest, 2008; 118:1085–1098.
39.
DelcenserieV, MartelD, LamoureuxM, et al.Immunomodulatory effects of probiotics in the intestinal tract. Curr Issues Mol Biol, 2008; 10:37–54.
