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Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in middle-age and older adults: A systematic review and meta-analysis

C. Custoderoa,b,⁎ , R.T. Mankowskia , S.A. Leea , Z. Chena,c , S. Wua,c , T.M. Maninia , J. Hincapie Echeverria , C. Sabbàb , D.P. Beaversd , J.A. Cauleye , M.A. Espelandd , R.A. Fieldingf , S.B. Kritchevskyd , C.K. Liuf , M.M. McDermottg , M.E. Millerd , R.P. Tracyh , A.B. Newmane , W.T. Ambrosiusd , M. Pahora , S.D. Antona,i

aDepartment of Aging and Geriatric Research, University of Florida, Gainesville, FL, United States

bDipartimento Interdisciplinare di Medicina, Clinica Medica Cesare Frugoni, University of Bari Aldo Moro, Bari, Italy

c Department of Biostatistics, University of Florida, Gainesville, FL, United States

dDepartment of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, United States

eDepartment of Epidemiology, University of Pittsburgh, Pittsburgh, PA, United States

f Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, United States

gDivision of General Internal Medicine and Geriatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States

hDepartment of Pathology & Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, United States

i Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, United States

Abstract

Growing evidence suggests chronic low-grade inflammation (LGI) as a possible mechanism underlying the aging process. Some biological and pharmaceutical compounds may reduce systemic inflammation and potentially avert functional decline occurring with aging. The aim of the present meta-analysis was to examine the association of pre-selected interventions on two established biomarkers of inflammation, interleukin-6 (IL-6), and Creactive protein (CRP) in middle-age and older adults with chronic LGI. We reviewed the literature on potential anti-inflammatory compounds, selecting them based on safety, tolerability, acceptability, innovation, affordability, and evidence from randomized controlled trials. Six compounds met all five inclusion criteria for our systematic review and meta-analysis: angiotensin II receptor blockers (ARBs), metformin, omega-3, probiotics, resveratrol and vitamin D. We searched in MEDLINE, PubMed and EMBASE database until January 2017. A total of 49 articles fulfilled the selection criteria. Effect size of each study and pooled effect size for each compound were measured by the standardized mean difference. I2 was computed to measure heterogeneity of effects across studies. The following compounds showed a significant small to large effect in reducing IL-6 levels: probiotics (−0.68 pg/ml), ARBs (−0.37 pg/ml) and omega-3 (−0.19 pg/ml). For CRP, a significant small to medium effect was observed with probiotics (−0.43 mg/L), ARBs (−0.2 mg/L), omega-3 (−0.17 mg/L) and metformin (−0.16 mg/L). Resveratrol and vitamin D were not associated with any significant reductions in either biomarker. These results suggest that nutritional and pharmaceutical compounds can significantly reduce established biomarkers of systemic inflammation in middle-age and older adults. The findings should be interpreted with caution, however, due to the evidence of heterogeneity across the studies.

Key Words: Chronic inflammation, Interleukin-6, C-reactive protein, Nutrient, Pharmaceutical, Adults

https://doi.org/10.1016/j.arr.2018.05.004

Received 22 February 2018; Received in revised form 21 May 2018; Accepted 21 May 2018

Ageing Research Reviews 46 (2018) 42–59

Available online 25 May 2018

1568-1637/ © 2018 Elsevier B.V. All rights reserved.

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