Replacing saturated or animal fats with monounsaturated or plant-based sources was associated with greater all-cause mortality among patients with nonmetastatic prostate cancer, primarily owing to deaths from cardiovascular disease and other cancers.

Researchers analyzed 4,884 patients with confirmed nonmetastatic prostate cancer in the Health Professionals Follow-Up Study, a prospective cohort of US male health professionals. Patients were diagnosed between 1986 and January 2019 and followed through December 2022. The mean age at diagnosis was 69.5 years, and 97% of patients self-reported as White. Dietary intake was assessed using validated food frequency questionnaires administered every 4 years, with postdiagnosis intake defined using the first questionnaire completed at least 6 months following diagnosis.

The primary outcomes were all-cause mortality and death from cardiovascular disease, prostate cancer, and cancers other than prostate cancer. Secondary outcomes included deaths from dementia, neurologic diseases, and respiratory diseases. Multivariable models accounted for demographic, clinical, dietary, and lifestyle factors, including age, disease stage, Gleason score, primary treatment, body mass index, smoking, physical activity, comorbidities, and prediagnosis fat intake.

During a median follow-up of 12.8 years, 3,040 patients died, including 803 from cardiovascular disease, 499 from other cancers, and 441 from prostate cancer. In fully adjusted analyses, patients in the highest quintile of saturated fat intake had 24% higher all-cause mortality compared with those in the lowest quintile. Estimated 10-year all-cause mortality was approximately 26% in the highest quintile vs 23% in the lowest, an absolute difference of 3 percentage points.

Dietary substitution analyses showed associations in the opposite direction. Replacing 5% of calories from saturated fat with monounsaturated fat was associated with 20% lower all-cause mortality. Replacing 10% of calories from animal fat with plant-based fat was associated with 16% lower all-cause mortality. Postdiagnosis total fat intake itself was not associated with all-cause mortality.

Cause-specific analyses suggested that the association between saturated fat and all-cause mortality was primarily owing to cardiovascular disease and other cancers. Patients in the highest vs lowest quintile of saturated fat intake had 42% higher cardiovascular mortality. The estimate for mortality from cancers other than prostate cancer was also 42% higher, although that association was not statistically significant. Higher monounsaturated fat intake, meanwhile, was associated with lower mortality, primarily owing to lower cardiovascular mortality.

The associations did not extend to prostate cancer–specific mortality. Researchers found no associations between the principal measures of postdiagnosis dietary fat intake and prostate cancer mortality. Although the main analysis suggested higher prostate cancer mortality with greater polyunsaturated fat intake, the association was attenuated and did not persist in sensitivity analyses, providing little support for a consistent association.

The study had several limitations. The researchers did not examine specific fatty acids, and self-reported food frequency questionnaires may have introduced measurement error. Postdiagnosis dietary intake was based on the first eligible questionnaire and was not subsequently updated, potentially resulting in exposure misclassification, and covariates were treated as fixed during follow-up. The cohort was also predominantly White and consisted of health professionals, which may limit generalizability to more racially, ethnically, and socioeconomically diverse populations. As an observational study, the analysis could not eliminate residual confounding, including from geographic location, socioeconomic status, and social support.

Overall, the findings linked higher saturated and animal fat intake following a diagnosis of nonmetastatic prostate cancer with greater all-cause mortality, while substitution analyses associated monounsaturated and plant-based fats with lower mortality. Importantly, the study did not find evidence that dietary fat intake was associated with prostate cancer–specific mortality. “Replacing saturated and animal fats with healthier plant-based fats was associated with mortality benefits,” wrote lead author Yiwen Zhang, PhD, of Harvard T.H. Chan School of Public Health, and colleagues.

Several authors reported industry relationships, including research funding, consulting or advisory roles, personal fees, or equity interests. The study received support from the National Institutes of Health and other research funding sources. No other disclosures were reported.

Source: JAMA Network Open