Effect of losartan and fish oil on plasma IL-6 and mobility in older persons. The ENRGISE Pilot randomized clinical trial

Authors: PAHOR, MARCO - University Of Florida; ANTON, STEPHEN - University Of Florida; BEAVERS, DANIEL - Wake Forest School Of Medicine; CAULEY, JANE - University Of Pittsburgh; FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; KRITCHEVSKY, STEPHEN - Wake Forest School Of Medicine; LEEUWENBURGH, CHRISTIAAN - University Of Florida; LEWIS, KRISTINA - Wake Forest School Of Medicine; LIU, CHRISTINE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LOVATO, LAURA - Wake Forest School Of Medicine; LU, JANE - University Of Florida; MANINI, TODD - University Of Florida; MCDERMOTT, MARY - Northwestern University; MILLER, MICHAEL - Wake Forest School Of Medicine; NEWMAN, ANNE - University Of Pittsburgh; RADZISZEWSKA, BARBARA - National Institute On Aging (NIA, NIH); STOWE, CYNTHIA - Wake Forest School Of Medicine; TRACY, RUSSELL - University Of Vermont; WALKUP, MICHAEL - Wake Forest School Of Medicine; WU, SAMUEL - University Of Florida; AMBROSIUS, WALTER - Wake Forest School Of Medicine

Submitted to: Journal of Gerontology Medical Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/30/2018
Publication Date: 12/12/2018
Citation: Pahor, M., Anton, S.D., Beavers, D.P., Cauley, J.A., Fielding, R.A., Kritchevsky, S.B., Leeuwenburgh, C., Lewis, K.H., Liu, C.K., Lovato, L., Lu, J., Manini, T.M., McDermott, M.M., Miller, M.E., Newman, A.B., Radziszewska, B., Stowe, C.L., Tracy, R.P., Walkup, M.P., Wu, S., Ambrosius, W.T. 2018. Effect of losartan and fish oil on plasma IL-6 and mobility in older persons. The ENRGISE Pilot randomized clinical trial. Journal of Gerontology Medical Science. https://doi.org/10.1093/gerona/gly277.
DOI: https://doi.org/10.1093/gerona/gly277

Interpretive Summary: Low-grade chronic inflammation, characterized by elevations in the blood of a protein called Interleukin-6 (IL-6), is a risk factor for reduced mobility in older adults. Both medicines known as Angiotensin receptor blockers and the dietary supplement omega-3 polyunsaturated fatty acids (omega-3) (fish oil) may reduce levels of the IL-6 protein and may improve mobility. The Enabling Reduction of low-Grade Inflammation in Seniors (ENRGISE) Pilot Study is a multicenter randomized clinical trial to examine the feasibility of testing whether omega-3 fish oil (omega-3) and the angiotensin receptor blocker (ARB) losartan (LO) alone or in combination can improve walking speed and lower inflammation over 12 months in older adults with slow walking speed and low-grade inflammation at baseline. A total of 289 participants were randomized (mean age 78.3 years, 47.4% women, 17.0% black). We found no effect of losartan alone, fish oil alone or the combination on changes in inflammation, as measured by blood levels of the IL-6 protein or on walking speed. Presently, these results do not support use of these interventions to prevent mobility loss in older adults at risk of disability with low-grade chronic inflammation.

Technical 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 (omega-3) may reduce IL-6 and may potentially improve physical function. To assess the main effects of the angiotensin receptor blocker losartan and omega-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, 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 required to be capable to of walking 400 meters at baseline. Participants were randomized in three strata 2 X 2 factorial to: a) losartan 50 to 100 mg/day or placebo (n=43), b) fish oil 1400 to 2800 mg/day or placebo (n=180), and c) with both (n=66). RESULTS. 289 participants were randomized (mean age 78.3 years, 47.4% women, 17.0% black). There was no effect of losartan (difference of means = -0.09+/-0.08 (SE), 95% CI: -0.25 to 0.67, P=0.25) or fish oil (0.035+/-0.053, 95% CI: -0.06 to 0.13, P=0.51) on the log of IL-6. There was no effect of losartan (-0.01+/-0.02], 95% CI: -0.04 to 0.03, P=0.71) or fish oil (0.01+/-0.01, 95% CI: -0.01 to 0.03, P=0.39) on walking speed (m/s). CONCLUSIONS. These results do not support use of these interventions to prevent mobility loss in older adults at risk of disability with low-grade chronic inflammation.