Effect of Losartan and Fish Oil on Plasma IL-6 and Mobility in Older Persons. The ENRGISE Pilot Randomized Clinical Trial

Abstract

Background: Low-grade chronic inflammation, characterized by elevations in plasma Interleukin-6 (IL-6), is an independent risk factor of impaired mobility in older persons. Angiotensin receptor blockers and omega-3 polyunsaturated fatty acids (ω-3) may reduce IL-6 and may potentially improve physical function. To assess the main effects of the angiotensin receptor blocker losartan and ω-3 as fish oil on IL-6 and 400 m walking speed, we conducted the ENRGISE Pilot multicenter randomized clinical trial.

Methods: The ENRGISE Pilot enrolled participants between April 2016 and June 2017, who participated for 12 months. Participants were aged ≥70 years with mobility impairment, had IL-6 between 2.5 and 30 pg/mL, and were able to walk 400 m at baseline. Participants were randomized in three strata 2 × 2 factorial to: (i) losartan 50-100 mg/d or placebo (n = 43), (ii) fish oil 1,400-2,800 mg/d or placebo (n = 180), and (iii) with both (n = 66).

Results: Two hundred eighty-nine participants were randomized (mean age 78.3 years, 47.4% women, 17.0% black). There was no effect of losartan (difference of means = -0.065 ± 0.116 [SE], 95% confidence interval [CI]: -0.293-0.163, p = .58) or fish oil (-0.020 ± 0.077, 95% CI: -0.171-0.132, p = .80) on the log of IL-6. Similarly, there was no effect of losartan (-0.025 ± 0.026, 95% CI: -0.076-0.026, p = .34) or fish oil (0.010 ± 0.017, 95% CI: -0.025-0.044, p = .58) on walking speed (m/s).

Conclusions: These results do not support the use of these interventions to prevent mobility loss in older adults at risk of disability with low-grade chronic inflammation.

Registration: Clinicaltrials.gov NCT02676466.

Keywords: Aging; Factorial design; Inflammation; Multicenter trial; Walking speed.

Figure 1.

Consort flow chart. Potential participants could be ineligible for more than one reason. *No self-reported difficulty walking ¼ mile or climbing steps, n = 1,183. *Current use of ACEI or ARB for those ineligible for both Losartan and Fish Oil trials, n = 623. *Currently taking omega-3/fish oil for those ineligible for both Losartan and Fish Oil trials, n = 344. *Usually use a walker to get around, n = 246. * Known/active inflammatory disease, n = 230. *Prior or current atrial fibrillation, for those ineligible for both Losartan and *Unable to walk one block, n = 204. *Current smoker, n = 185. *Currently receiving physical therapy for gait, balance, n = 123. *Use of potassium sparing diuretics for those ineligible for both Losartan and Fish Oil trials, n = 96. *Lives outside area/relocations, n = 86. *Neurologic conditions, impaired mobility, n = 75. *Allergy to fish, shell fish, and/or fish oil for those ineligible for both Losartan and Fish Oil trials, n = 70. *Acute Infection, n = 66. *>14 alcohol drinks/week, n = 53. *Severe pulmonary disease, n = 47. *Participation in another intervention study, n = 47. *Consumed more than two servings per week of fish in the past year for those ineligible for both Losartan and Fish Oil trials, n = 44. *Age <70, n = 41.

Figure 2.

Change in IL-6 pg/mL over time. (A) Losartan (solid line) vs no losartan (dotted line). (B) Fish oil (solid line) vs no fish oil (dotted line). (C) Losartan + fish oil (solid line) vs placebo (dotted line).

Figure 3.

Change in 400 m walk speed m/s over time. (A) Losartan (solid line) vs no losartan (dotted line). (B) Fish oil (solid line) vs no fish oil (dotted line). (C) Losartan + fish oil (solid line) vs placebo (dotted line).