Cited by 507Health disparities and outcomesCardiac Health and Mental HealthDeath Anxiety and Social Exclusion

The DOI matches its Crossref record; 149 of the 149 references it cites were found in a registry or an index; 6 of the 9 sources its claims cite were checked for support.

A systematic review and meta-analysis of 90 cohort studies of social isolation, loneliness and mortality

Open access

Published version of a preprint

Abstract

Abstract Background We aimed to assess the associations between social isolation (SI) and the risk of mortality from all causes, cardiovascular disease, and cancer. Methods This was a systematic review and meta-analysis of prospective cohort studies.We searched electronic databases, including PubMed, Web of Science, and Embase, from inception until October 2021, as well as the references of retrieved articles. Prospective studies reporting risk estimates for the association between SI and mortality from all causes, cardiovascular diseases, and cancer in adults aged 18 or older were included in the analyses. Data were screened and extracted independently by two investigators. The fully adjusted effect sizes in the original studies were analyzed, and summary analyses were performed using a fixed-effects or random-effects model, according to the heterogeneity among studies. Subgroup analyses, meta-regression, and sensitivity analyses were performed to evaluate the heterogeneity and robustness of the findings. Simple linear regression was used to analyze the changing trends in social network index grade and risk of mortality. The risk of publication bias was tested using funnel plots and Egger’s and Begg’s tests (each significant at P < 0.05). The trim-and-fill method was used to adjust for the influence of potentially unpublished studies on pooled effect estimates when statistical tests indicated publication bias. The study protocol was registered with PROSPERO (reg. NO CRD42022299959) Results A total of 50 prospective cohort studies with 1,951,661 individuals were included for analysis. The duration of follow-up among included studies ranged from 6 months to 24.4 years. In pooled analyses, SI was significantly associated with an increased risk of mortality from all causes (pooled effect size, 1.22; 95% confidence interval [CI], 1.16 to 1.29; I2 = 77.6%), cardiovascular disease (1.35; 95% CI 1.25 to 1.45, I2 = 65.5%), and cancer (1.23; 95% CI 1.18 to 1.27, I2 = 44.2%) in the general population. Linear regression showed that social network index grade was significantly correlated with the risk of all-cause mortality (P < 0.001). Additionally, the pooled effect estimate for all-cause mortality in patients with breast cancer was 1.51 (95% CI 1.34 to 1.70), and that for cancer-specific mortality was 1.33 (95% CI 1.02 to 1.75). There was a 28% increased risk of all-cause mortality in socially isolated patients with cardiovascular disease (95% CI 1.10 to 1.48). There was no evidence of a positive association between SI and cancer-specific mortality in patients with colorectal cancer (1.07, 95% CI 0.96 to 1.20). Conclusions SI was associated with at least a 20% increased risk of all-cause mortality, cardiovascular disease mortality, and cancer mortality. We highlight that social isolation contributes to chronic disease and mortality, with efforts to improve social isolation likely to have benefits in well-being and survival.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and meta-analysis of 50 prospective cohort studies (1,951,661 individuals) found that social isolation was associated with increased mortality from all causes, cardiovascular disease, and cancer in the general population. The highest risk was for cardiovascular mortality, and associations were also observed in patients with cardiovascular disease and breast cancer.

Key findings

  • Social isolation was significantly associated with all-cause mortality (pooled effect estimate 1.31, 95% CI 1.23–1.38; I² = 77.6%), which remained after trim-and-fill adjustment (1.22, 95% CI 1.16–1.29).
  • Pooled estimates were 1.35 (95% CI 1.25–1.45, I² = 65.5%) for cardiovascular/circulatory disease mortality and 1.23 (95% CI 1.18–1.27, I² = 44.2%) for cancer mortality.
  • In patient populations: all-cause mortality was 1.28 (95% CI 1.10–1.48) in patients with CVD; in breast cancer, all-cause mortality was 1.51 (95% CI 1.34–1.70) and cancer-specific mortality 1.33 (95% CI 1.02–1.75). No significant association was found for cancer-specific mortality in colorectal cancer (1.07, 95% CI 0.96–1.20).
  • Social Network Index grade was significantly correlated with all-cause mortality risk (P < 0.001), with mortality increasing as isolation increased.

Methods

  • Systematic review and meta-analysis of prospective cohort studies; PubMed, Web of Science, and Embase searched from inception to October 2021, plus reference lists; protocol registered with PROSPERO (CRD42022299959).
  • 50 prospective cohort studies with 1,951,661 participants aged ≥18 years (most ≥50 years); follow-up ranged from 6 months to 24.4 years; 23 studies were from the United States.
  • Fully adjusted effect sizes (HR/RR/OR with 95% CIs) were pooled using fixed- or random-effects models according to heterogeneity (I² ≥ 50% random effects); subgroup analyses, meta-regression, sensitivity analyses, and publication bias tests (funnel plots, Egger's and Begg's tests, trim-and-fill) were performed.

Limitations

  • Stated: adjustment factors varied greatly across original studies, making the source of heterogeneity complex and difficult to trace; potential unknown confounders may remain; definitions and instruments for social isolation were not consistent across studies; most included studies came from high-income countries; and early deaths were not excluded in the original studies.
  • Evident from the text: significant publication bias was detected for the all-cause mortality analysis (Egger's P = 0.037; Begg's P = 0.036), and heterogeneity was substantial (I² = 77.6%).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41562-023-01617-6

Cites

149 of 149 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Figures

Figure 1 Flow Figure1
Figure 1 Flow Figure1CC-BY · From the PDF
Figure 2 Association Figure2
Figure 2 Association Figure2CC-BY · From the PDF
Figure 3 Association Figure3
Figure 3 Association Figure3CC-BY · From the PDF
Figure 4 Association Figure4
Figure 4 Association Figure4CC-BY · From the PDF
Figure 5 Association Figure5
Figure 5 Association Figure5CC-BY · From the PDF

Verification

Claims the paper makes

28 Own result · 22 Own method · 13 Own interpretation · 4 Couldn’t confirm · 3 No full text of the sources · 2 No basis given · 1 Partly supported · 1 Not checked yet · accuracy not yet measured

Show all 41 claims

  • Probably not a substantial claim. 18
  • It may state two separate claims as one. 17
33 of 33
  • The paper relies on this without support.

    Different methods used to assess social isolation in the included studies measure the same underlying exposure sufficiently to be pooled in a single meta-analysis.

    “We included all studies with SI evaluated using different methods (detailed de nitions in Table S2) in the original studies.”
  • The paper relies on this without support.

    Hazard ratios, risk ratios, and odds ratios from the included studies are comparable and can be combined to produce pooled effect estimates.

    “HRs and RRs (along with 95% CIs) for comparisons of SI with non-SI or graded variables in the original studies were summarized to calculate the pooled effect estimates for the association between SI and mortality outcomes.”
  • The paper relies on this without support.

    The most fully adjusted effect estimates from the included studies adequately control for confounding, so the pooled associations can be interpreted as independent effects of social isolation.

    “If the included studies reported both crude and multivariable-adjusted effect estimates, we extracted the most fully adjusted outcomes in the present meta-analysis.”
  • The paper relies on this without support.

    The observed associations between social isolation and mortality reflect a causal effect of social isolation rather than residual confounding or reverse causation.

    “We highlight that social isolation contributes to chronic disease and mortality”
  • The paper relies on this without support.

    The search strategy identified all relevant studies.

    “We searched PubMed, Web of Science, and Embase for studies published in English between database inception and October 2021.”
  • The paper relies on this without support.

    This was the first study to comprehensively evaluate the association between SI and mortality from all causes, CVD, and cancer.

    “To the best of our knowledge, this was the rst study to comprehensively evaluate the association between SI and mortality from all causes, CVD, and cancer.”
  • The paper relies on this without support.

    The association between SI and cancer mortality was systematically reviewed for the first time, as was the relationship between SI and mortality in patients with CVD and cancer.

    “The association between SI and cancer mortality was systematically reviewed for the rst time, as was the relationship between SI and mortality in patients with CVD and cancer.”
7 of 7

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

2 of 2

Citations

Cites

Show all 148 references

Research works printed but not linked: 2

  1. National Academies of Sciences, Engineering, and Medicine Social Isolation and Loneliness in Older Adults: Opportunities for the Health Care System (National Academies Press, 2020).
  2. ICD-9-CM. International Classification of Diseases, 9th revision, Clinical Modification. 3d edition, volumes 1, 2 and 3. Official authorized addendum effective October 1, 1990–HCFA. J. Am. Med. Rec. Assoc. 61, 1–35 (1990). Suppl.

Cited by

Sorted by citations

Items 401–500 of 507

Metadata

Authors
Wang, F., Gao, Y., Han, Z., Yu, Y., Long, Z., Jiang, X., Wu, Y., Pei, B., Cao, Y., Ye, J., Wang, M., & Zhao, Y.
Affiliations
Harbin Medical University (CN)
Corresponding author
  • Wang, Maoqing
  • Zhao, Yashuang
Venue
Nature Human Behaviour
Published
2023-06-19
Volume
7
Issue
8
Pages
1307-1319
ISSN
2397-3374 (ISSN-L)
OpenAlex
W4381190169
Cited by
507
References
148
Citations by year
2026: 190 · 2025: 173 · 2024: 117 · 2023: 26
FWCI
20.16
Type
journal article
Language
en
Open access
Locations
  • Nature Human Behaviour (publishedVersion)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
Dr. Wu Lien teh Science Foundation of Harbin Medical University
Topics
  • Social Sciences › Health › Health disparities and outcomes
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
  • Social Sciences › Psychology › Social Psychology › Death Anxiety and Social Exclusion
Keywords
social isolation, loneliness, mortality, all-cause mortality, cardiovascular mortality, cancer mortality, breast cancer, social determinants of health
MeSH terms
Adult, Breast Neoplasms, Cardiovascular Diseases, Female, Humans, Loneliness, Prospective Studies, Social Isolation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-11-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-11-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Cited sources are checked with a language model’s help (gpt-6-sol).

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review