Saturated Fat Intake Linked to Greater Mortality in Nonmetastatic Prostate Cancer

Postdiagnosis intake of saturated and animal fats was associated with greater all-cause mortality among patients with nonmetastatic prostate cancer, driven primarily by cardiovascular disease and non-prostate-cancer deaths, according to results from the observational Health Professionals Follow-Up Study (HPFS; NCT00005182) published in JAMA Network Open.¹ Replacing animal fats with plant-based sources was associated with a meaningful reduction in mortality risk.

Among 4884 patients, 3040 deaths from any cause were confirmed. In fully adjusted models, patients in the highest quintile of saturated fat intake had a 24% greater risk of all-cause death compared with those in the lowest quintile (HR, 1.24; 95% CI, 1.05-1.47), with evidence of a linear trend (P = .01). The estimated 10-year absolute risk of all-cause mortality was 23.4% for patients in the lowest quintile of saturated fat intake and 26.4% for those in the highest quintile, for an absolute risk difference of 3.0%. Replacing 5% of calories from carbohydrates with saturated fat was also associated with higher all-cause mortality (HR, 1.15; 95% CI, 1.03-1.28).

The association between saturated fat and elevated all-cause mortality was driven primarily by cardiovascular disease deaths and deaths from other cancers. Patients in the highest quintile of saturated fat consumption had a 42% greater cardiovascular mortality risk compared with those in the lowest quintile (HR, 1.42; 95% CI, 1.02-1.98), and an HR of 1.42 (95% CI, 0.93-2.17) for death from other cancers. Replacing 5% of calories from carbohydrates with saturated fat was associated with a 37% higher cardiovascular mortality risk (HR, 1.37; 95% CI, 1.11-1.71). Animal fat, a major dietary source of saturated fats, was also positively associated with all-cause mortality (HR, 1.14; 95% CI, 0.97-1.33) and death from other cancers (HR, 1.49; 95% CI, 1.00-2.21).

Substituting healthier fat sources for animal and saturated fats was associated with mortality reductions. Replacing 10% of calories from animal fats with plant-based fat sources was associated with a 16% lower risk of all-cause death (HR, 0.84; 95% CI, 0.76-0.93). Similarly, replacing 5% of saturated fat calories with monounsaturated fats was associated with a 20% lower all-cause mortality risk (HR, 0.80; 95% CI, 0.70-0.91). Patients in the highest quintile of monounsaturated fat intake had a cardiovascular mortality HR of 0.70 (95% CI, 0.50-0.97) compared with those in the lowest quintile. There were no associations between postdiagnosis intake of any dietary fat type and prostate cancer-specific mortality.

“In this cohort of patients with nonmetastatic prostate cancer, higher intake of saturated and animal fats after prostate cancer diagnosis was associated with higher all-cause mortality, owing to increased death from cardiovascular disease and other cancers,” wrote senior study author Lorelei Mucci, ScD, MPH, professor of epidemiology at the Harvard T.H. Chan School of Public Health, with study coinvestigators in the publication.¹ “Replacing saturated and animal fats with healthier plant-based fats was associated with mortality benefits. This study coupled with prior epidemiologic studies provides evidence-based recommendations for patients and clinicians around dietary fat consumption to improve survivorship outcomes in the clinical setting of nonmetastatic prostate cancer.”

The HPFS is a prospective cohort of 51,529 US male health professionals aged 40 to 75 years that is ongoing since 1986. This analysis included participants with confirmed nonmetastatic prostate cancer, which included clinical stages T1a-T3b, N0/NX, M0/MX, who were diagnosed between 1986 and January 2019 and followed up through December 2022. The statistical analysis was conducted from July 2024 to May 2026.

Among the 4884 patients included, the mean age at diagnosis was 69.5 years (SD, 6.9); 97% of patients self-reported as White and 62% received a diagnosis of clinical stage T1 disease. Dietary data were collected every 4 years from validated semiquantitative food frequency questionnaires. Postdiagnosis fat intake was defined from the first questionnaire returned at least 6 months after diagnosis to avoid reverse causation from early post-diagnosis changes.

The primary outcomes of the study were all-cause mortality and death from cardiovascular disease, prostate cancer, other cancers, and other causes. HRs and CIs from multivariable Cox proportional hazards regression and multivariate nutrient-density models examined associations with mortality, adjusting for demographic, clinical, and lifestyle factors.

The authors noted several limitations, including that the study did not examine specific fatty acids—an important caveat given that individual fatty acids within the same category may have different associations with outcomes. Postdiagnosis dietary fat intake was not updated during follow-up, potentially introducing exposure misclassification. The cohort was composed predominantly of White health professionals, limiting generalizability to more racially, ethnically, and socioeconomically diverse prostate cancer populations; replication in more diverse cohorts is needed. As an observational study, residual confounding cannot be excluded.

These findings extend prior work from the HPFS, in which replacing 5% of calories from carbohydrates with saturated fats was associated with a 30% higher all-cause mortality in an analysis limited to 1064 deaths. The current analysis added 12 additional years of follow-up for a final count of 3040 deaths. In the Physicians’ Health Study, patients who replaced 10% of animal fat calories with plant-based fat had a 44% lower mortality risk, consistent with the substitution effects observed in the current study.²

References

1. Zhang Y, Shanahan MR, Guard HE, et al. Dietary fat intake and mortality among patients with nonmetastatic prostate cancer. JAMA Network Open. 2026;9(9):e2630693. doi:10.1001/jamanetworkopen.2026.30693
2. Van Blarigan EL, Kenfield SA, Yang M, et al. Fat intake after prostate cancer diagnosis and mortality in the Physicians’ Health Study. Cancer Causes Control. 2015;26(8):1117-1126. doi:10.1007/s10552-015-0606-4