Table 1

Overview of the included meta-analyses

Publication
Embedded Imageresults:
Social connectionClinical outcomeStudy designAge:
M (SD), range, or cut-off
Literature search: timespanRange of follow- upN databases searchedQuality score
Studies on physical health
Besora-Moreno et al23Living aloneMalnutrition/
malnutrition risk
Cross-sectional60+01.2000–12.2018n.a.2L
Results:Living aloneCombined effectOR=1.92 (95% CI: 1.73 to 2.14); k=10; N=9042
Heidari Gorji et al25Living alone, social isolation, lonelinessHospital readmission in patients with heart failureLongitudinal70.87 (8.62)Up to 11.201813 months6H
Results:Any type of poor social connectionCombined effectOR=1.55 (95% CI: 1.39 to 1.73); k=13; N=6468
Living alone or social isolationCombined effectOR=1.52 (95% CI: 1.24 to 1.86); k=6; N=3812
LonelinessCombined effectOR=1.63 (95% CI: 1.31 to 2.01); k=7; N=2656
Holt-Lunstad et al4Living alone, social isolation, lonelinessEarly mortalityLongitudinal66.00 (n.r.)01.1980–02.20147.1 years5L
Results:Living aloneUnadjusted studiesOR=1.51 (95% CI: 1.32 to 1.74); k=20; N=n .r.
Living aloneStudies with multiple covariatesOR=1.32 (95% CI: 1.14 to 1.53); k=25; N=n .r.
Social isolationUnadjusted studiesOR=1.83 (95% CI: 1.27 to 2.63); k=3; N=n .r.
Social isolationStudies with multiple covariatesOR=1.29 (95% CI: 1.06 to 1.56); k=14; N=n .r.
LonelinessUnadjusted studiesOR=1.49 (95% CI: 1.22 to 1.84); k=8; N=n .r.
LonelinessStudies with multiple covariatesOR=1.26 (95% CI: 1.04 to 1.53); k=13; N=n .r.
Jain et al24Living aloneReduced vaccine uptake in older adultsCross-sectional*†60+Up to 02.2016n.r.2M
Results:Living aloneSeasonal influenza vaccineOR=1.39 (95% CI: 1.16 to 1.68); k=9; N=40 551
Living alonePneumococcal vaccineOR=1.71 (95% CI: 1.20 to 2.46); k=1; N=1702
Kojima et al21Living aloneFrailty in older adultsCross-sectional† and longitudinal†60+2000–02.2019n.r.1L
Results:Living aloneCross-sectional studiesOR=1.28 (95% CI: 1.13 to 1.45); k=44; N=1 13 374
Subanalysis: only menOR=1.71 (95% CI: 1.49 to 1.96); k=20; N=n .r.
Subanalysis: only womenOR=1.00 (95% CI: 0.83 to 1.20); k=22; N=n .r.
Subanalysis:≥60,<70 years oldOR=1.67 (95% CI: 1.51 to 1.86); k=4; N=n .r.
Subanalysis:≥80 years oldOR=0.96 (95% CI: 0.69 to 1.31); k=6; N=n .r.
Living aloneLongitudinal studiesOR=0.88 (95% CI: 0.76 to 1.03); k=6; N=38 549
Maes et al22LonelinessChronic physical conditions in children/adolescentsCross-sectional*Children<12 and adolescents<211987–06.2016n.r.4L
Results:LonelinessCombined effect (excluding three outliers)g=0.17 (95% CI: 0.03 to 0.30); k=40; N=3981
Subanalysis: control group studiesg=0.13 (95% CI: 0.01 to 0.26); k=23; N=2995
Subanalysis: hearing/visual problemsg=0.43 (n.r.); k=8; N=770
Rico-Uribe et al19LonelinessEarly
mortality
Longitudinal†Mainly 50+Up to 06.2016n.r.4H
Results:LonelinessCombined effectHR=1.22 (95% CI: 1.10 to 1.35); k=31; N=77 220
Subanalysis: only menHR=1.44 (95% CI: 1.19 to 1.76); k=7; N=5815
Subanalysis: only womenHR=1.26 (95% CI: 1.07 to 1.48); k=7; N=10 248
Smith et al20Social isolation, lonelinessInflammation
markers
Cross-sectional*16+Up to 07.2019n.r.5H
Results:Social isolationC reactive protein: unadjusted studiesr=0.186 (95% CI: .063 to 0.303); k=7; N=41 126
C reactive protein: adjusted studiesr=0.021 (95% CI: .051 to 0.092); k=11; N=41 911
Fibrinogen: unadjusted studiesr=0.103 (95% CI: 0.043 to 0.163); k=6; N=15 421
Fibrinogen: adjusted studiesr=0.039 (95% CI: 0.011 to 0.067); k=6; N=22 161
Interleukin-6: unadjusted studiesr=0.267 (95% CI: −0.341 to 0.718); k=4; N=12 291
Interleukin-6: adjusted studiesr=-.003 (95% CI: −0.148 to 0.141); k=6; N=14 243
LonelinessC reactive protein: unadjusted studiesr=0.047 (95% CI: −0.003 to 0.098); k=8; N=17 835
C reactive protein: adjusted studiesr=0.023 (95% CI: −0.018 to 0.065); k=6; N=19 292
Fibrinogen: unadjusted studiesr=0.006 (95% CI: −0.057 to 0.070); k=3; N=1806
Fibrinogen: adjusted studiesr=0.037 (95% CI: −0.015 to 0.089); k=4; N=7672
Interleukin-6: unadjusted studiesr=0.082 (95% CI: −0.001 to 0.163); k=4; N=4219
Interleukin-6: adjusted studiesr=0.070 (95% CI: .015 to 0.124); k=2; N=1451
Steptoe and Kivimäki17Social isolation, lonelinessCardiovascular diseaseLongitudinal†n.r.Up to 2011n.r.n.r.CL
Results:Social isolation or
loneliness
Combined effectRR=1.51 (95% CI: 1.21 to 1.88); k=7; N=n .r.
Valtorta et al18Social isolation, lonelinessCoronary heart disease and strokeLongitudinal†18+Up to 05.20153 to 21 years16H
Results:Social isolation or
loneliness
Coronary heart diseaseRR=1.29 (95% CI: 1.04 to 1.59); k=11; N=n .r.
Social isolationStroke incidenceRR=1.32 (95% CI: 1.04 to 1.68); k=9; N=n .r.
Studies on mental health
Chang et al34Living alone, lonelinessLate-life suicidal ideationCross-sectional*‡50+01.2000–11.2016n.r.7L
Results:Living aloneCombined effectOR=1.38 (95% CI: 1.19 to 1.61); k=8; N=1 02 401
LonelinessCombined effectOR=2.24 (95% CI: 1.73 to 2.90); k=3; N=58 482
Chatterjee et al39Social isolation, lonelinessDepression in civilians after 9/11Longitudinal43.78 (n.r.)09.2001–07.2016n.r.3L
Results:Social isolation or lonelinessCombined effectOR=1.68 (99.5% CI:1.13 to 2.49); k=4; N=27 395
Chau et al37LonelinessPsychosisCross-sectional*‡Adults (mainly)Up 10.2018n.r.5M
Results:LonelinessPositive symptomsr=0.302 (95% CI: 0.243 to 0.359); k=30; N=17 832
Subanalysis: clinical populationsr=0.149 (95% CI: 0.057 to 0.238); k=14; N=n .r.
Subanalysis: non-clinical populationsr=0.389 (95% CI: 0.232 to 0.526); k=5; N=n .r.
Subanalysis: mixed populationsr=0.366 (95% CI: 0.308 to 0.422); k=12; N=n .r.
Subanalysis: Paranoiar=0.448 (95% CI: 0.371 to 0.519); k=7; N=n .r.
Subanalysis: Hallucinationsr=0.201 (95% CI: 0.101–.297); k=10; N=n .r.
LonelinessNegative psychotic symptomsr=0.347 (95% CI: 0.239–.446); k=15; N=5567
Subanalysis: clinical populationsr=0.127 (95% CI: 0.029 to 0.223); k=9; N=n .r.
Subanalysis: non-clinical populationsr=0.479 (95% CI: 0.351 to 0.589); k=4; N=n .r.
Subanalysis: mixed populationsr=0.547 (95% CI: 0.464 to 0.620); k=2; N=n .r.
Choi and Smith32Social isolationAdolescents’ smoking behavioursCross-sectional<19n.r.n.a.3CL
Results:Social isolationNetwork position: isolate vs memberOR=1.55 (95% CI: 1.32 to 1.81); k=8; N=5067
Network position: isolated vs liaisonOR=1.49 (95% CI: 1.07 to 2.07); k=8; N=5067
Erzen and Çikrikci35LonelinessDepressionCross-sectional*AdultsUp to 01.2018n.r.2CL
Results:LonelinessCombined effectr=0.50 (95% CI: 0.44 to 0.55); k=88; N=40 068
Subanalysis: clinical populationsr=0.54 (95% CI: 0.38 to 0.67); k=10; N=n .r.
Subanalysis: other populationsr=0.44 (95% CI: 0.16 to .66); k=12; N=n .r.
Evans et al28Social isolationCognitive functioningLongitudinal50+Up to 01.20182–24 years4M
Results:Social isolationCombined effectr=0.054 (95% CI: 0.043 to 0.065); k=51; N=1 02 035
Subanalysis: global measuresr=0.061 (95% CI: 0.044 to 0.079); k=43; N=74 933
Subanalysis: memoryr=0.050 (95% CI: 0.028 to 0.072); k=13; N=35 230
Subanalysis: executive functioningr=0.031 (95% CI: 0.015 to 0.047); k=7; N=30 528
Kuiper et al29Social isolation, lonelinessRisk of dementiaLongitudinal†60+Up to 07.20122 to 15 years3M
Results:Social isolationLow social network sizeRR=1.17 (95% CI: 0.92 to 1.48); k=5; N=7749
Social isolationLow level of participationRR=1.41 (95% CI: 1.13 to 1.75); k=6; N=7687
Social isolationLow frequency of contactsRR=1.57 (95% CI: 1.32 to 1.85); k=8; N=15 762
LonelinessFeeling lonelyRR=1.58 (95% CI: 1.19 to 2.09); k=3; N=3252
LonelinessLow satisfaction with social networkRR=1.25 (95% CI: 0.96 to 1.62); k=4; N=6207
Lara et al30LonelinessDementia and mild cognitive impairmentLongitudinal†50+Up to 11.2018n.r.6H
Results:LonelinessCombined effectRR=1.26 (95% CI: 1.14 to 1.40); k=8; N=33 555
Maes et al31LonelinessSocial anxiety in children/adolescentsCross-sectional and longitudinal15.59 (4.27)1981–06.20161.25 to 72 months4CL
Results:LonelinessCross-sectional effectsr=0.46 (95% CI: 0.43 to 0.48); k=98; N=41 776
LonelinessLongitudinal/cross-lagged effectsr=0.12 (95% CI: 0.04 to 0.21); k=10; N=3995
Mahon et al33LonelinessDepression and social anxiety in adolescenceCross-sectional*Adolescents (11–23)1980–2004n.r.4CL
Results:LonelinessDepressionr=0.61 (n.r.); k=30; N=17 691
Subanalysis: outliers removedr=0.55 (n.r.); k=18; N=6058
LonelinessAnxietyr=0.41 (n.r.); k=12; N=3853
Subanalysis: outliers removedr=0.35 (n.r.); k=10; N=2705
Michalska da Rocha et al36LonelinessPsychosisCross-sectional*‡AdultsUp to 02.2016n.r.4H
Results:LonelinessCombined effectr=0.32 (95% CI: 0.20 to 0.44); k=13; N=15 647
Penninkilampi et al27Living alone, social isolation, lonelinessRisk of dementiaLongitudinal and case-control60+01.2012–05.20175.9 years8L
Results:Any type of poor social connectionCombined effectRR=1.41 (95% CI: 1.21 to 1.65); k=15; N=2 330 163
Social isolationCombined effectRR=1.59 (95% CI: 1.31 to 1.93); k=6; N=25 373
Living aloneCombined effectRR=1.41 (95% CI: 1.07 to 1.84); k=4; N=5401
LonelinessCombined effectRR=1.38 (95% CI: 0.98 to 1.94); k=4; N=4698
Teo et al38Living aloneSocial anxiety disorderCross-sectional*Adults (mainly)01.1980–02.2011n.r.4M
Results:Living aloneCombined effectOR=1.73 (95% CI: 1.34 to 2.24); k=4; N=12 831
Subanalysis: large survey studiesOR=1.70 (95% CI: 1.38 to 2.10); k=3; N=12 773
Xiu-Ying et al26Living aloneLate life depressionCross-sectional and longitudinal55+1966–08.2007n.r.3CL
Results:Living aloneCross-sectional effectsOR=1.44 (95% CI: 1.04 to 1.99); k=16; N=34 090
Subanalysis: versus living with familyOR=2.59 (95% CI: 1.60 to 4.20); k=5; N=12 537
Living aloneLongitudinal/cross-lagged effectsRR=1.27 (95% CI: 0.89 to 1.80); k=4; N=1345
Yuan et al40Living alonePostacute coronary syndrome depressionLongitudinal and case-control19+01.1996–03.2018n.r.4L
Results:Living aloneCombined effectOR=1.17 (95% CI: 1.12 to 1.22); k=11; N=n .r.
  • For each result, we specify the type of social connection, the focus of the (sub)analysis, followed by the reported effect size (in brackets: CIs), as well as included numbers of independent studies and participants. Most meta-analyses included studies both with adjusted and unadjusted effect sizes (typically controlling for potential confounders like age, sex, education, socioeconomic status, chronic conditions, depression or anxiety). Unless specified in the table, the authors did not indicate a preference for adjusted or for unadjusted effect sizes. Note that adequate consideration of confounding is also in part reflected in the quality scores. Effect sizes printed in boldface are statistically significant at alpha=0.05.

  • *These studies included different study designs and extracted cross-sectional data or aggregated longitudinal and cross-sectional data.

  • †Effect sizes with adjustment for confounders were preferred in this meta-analysis.

  • ‡Effect sizes with no or minimal adjustment were preferred in this meta-analysis.

  • CL, critically low; H, high; L, low; M, moderate; n.a., not applicable; n.r., not reported.