Frequent ultra-processed food consumption raises mortality risks, especially in women

Long-term consumption of ultra-processed foods significantly raises mortality risks, particularly from cardiovascular and respiratory diseases, with metabolite data providing fresh insights into the underlying health impacts.

Metabolomic Insights: The study identified 900 metabolites, of which 93 were directly linked to ultra-processed food (UPF) intake, providing a deeper understanding of the biochemical pathways affected by these foods.

In a recent study published in the journal Clinical Nutrition, researchers used a large cohort comprising 27,670 participants, plasma metabolite analyses, and hazard models to evaluate the impacts of ultra-processed foods (UPFs) on metabolite signatures and mortality risk. The long-term follow-up study (median = 23.3 years) revealed that UPF intake was positively associated with all-cause mortality, particularly in females.

UPF intake was significantly associated with increased risks of cardiovascular disease (CVD) mortality, premature mortality, and respiratory disease mortality, while no statistically significant association was found with cancer mortality. Plasma metabolite experiments further demonstrated that ninety-three metabolite signatures were associated with all-cause mortality risk.

This study provides the first empirical evidence for the adverse mortality-accelerating effects of frequent UPF intake, validating public health campaigns and positive dietary intervention initiatives.

Background

The NOVA classification system defines ultra-processed foods (UPFs; Group 4 Foods) as food derivatives characterized by a high degree of transformation and use of many ingredients, including food additives and processed raw material, with little to no nutritional content. UPFs present a host of consumer-friendly attractions, including taste, inexpensiveness, and easy accessibility, resulting in an explosion in their popularity in recent decades.

Sex-Specific Risks: UPF consumption had a linear association with mortality in women but followed a J-shaped curve in men, suggesting differing mortality risks based on sex.

Western countries and developed regions have contributed disproportionately to UPFs' popularity, with the food products comprising significant portions of the 'Western Dietary Pattern,' the staple diet of 14-44% of Europeans and almost 60% of the United States (US).

Unfortunately, a growing body of observational evidence over the past five years has suggested significant chronic health concerns highly correlated with increasing UPF consumption, leading to public health agencies, including the World Health Organization (WHO) and the US Centers for Disease Prevention and Control (CDC) recommending against their intake.

Unfortunately, clinically validated empirical evidence for the adverse associations of UPFs remains limited and confounding results, which can be attributed to previous studies' low sample sizes, insufficient follow-up durations, and predominantly White American racial focus. Establishing negative outcomes following UPF consumption would lend public health agencies a much-needed scientific voice to curb this silent pandemic.

About the study

The present study evaluated the associations between UPF intake (subdivided into seven UPF subgroups) and mortality (all-cause, premature, cancer, CVD, and respiratory). It addressed the limitations of previous works by leveraging 23.3 years of follow-up data from the Malmö Diet and Cancer (MDC) cohort study comprising more than 74,000 Swedish citizens between the ages of 45 and 73, 30,446 of whom partook in baseline screening.

Screening involved two rounds of questionnaires comprising items on socioeconomic and lifestyle factors alongside anthropometric measurement recordings. Participants with incomplete dietary records were excluded, leaving a final cohort size of 27,670. A subset of 6,103 participants were simultaneously enrolled in the Malmö Diet and Cancer Cardiovascular Cohort (MDC-CC), allowing access to their blood lipid and lipoprotein subfractions for metabolomic investigations.

Weekly dietary UPF intake data was obtained using a custom 168-item questionnaire and an additional hour-long nutritional interview. Metabolomics investigations were carried out using untargeted liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).

Finally, outcome ascertainment data (mortality records) were obtained from the National Board of Health and Welfare, Statistics in Sweden, and the Swedish National Tax Agency. Deaths occurring in participants under the age of 75 years were classified as 'premature,' and disease-associated causes of death were recorded using the International Classification of Diseases (ICD) codes. Outcomes were evaluated using Cox Proportional Hazard Ratios (HRs), adjusted for covariates (age, sex, etc.).

Study findings

Lipid Profiles: Participants with higher UPF intake had unfavorable lipid and lipoprotein profiles, including reduced levels of large HDL (good cholesterol) and increased levels of small LDL (bad cholesterol).

Of the 27,670 study participants, 60.7% were female, with a mean age of 58.1 years representing the cohort. During the median 23.3 years of follow-up, ~41% (n = 11,333) of the cohort died of chronic diseases, including cancers (3,938), CVD (3,709), or respiratory diseases (758). Of these, 3,672 were considered 'premature' mortality.

Dietary item analyses identified that UPFs comprised 13.4% of the cohort’s total food intake. Participants with higher UPF intake were more likely to be female, older, never smokers, and low alcohol consumers. High UPF intake was also associated with education status (low), body mass index (BMI, high), and cancer prevalence. The main contributors to UPF intake were breakfast cereals (26%), beverages (23.3%), sugary products (18.4%), sauces (15.5%), and meat and fish (13.6%).

Hazard ratio analyses revealed significant, nonlinear positive associations between UPF consumption and all-cause mortality (P_nonlinear = 0.022). Analyses of covariates elucidated that this association was stronger and linear in females and weaker with a J-shaped curve in males. HRs for all-cause mortality, premature mortality, CVD-associated mortality, and respiratory diseases were 1.06, 1.06, 1.05, and 1.08, respectively. Surprisingly, no associations between UPF consumption and cancer mortality risk could be established.

Metabolic signature analyses identified more than 900 metabolites of interest, with 93 being significantly associated with UPF intake and observed to dramatically increase mortality risk (HR = 1.23) by ~23%. In contrast, minimally processed and processed foods were observed to reduce mortality risk (HR = 0.87) by up to 13%.

Conclusions

The present study provides the first empirical evidence for the adverse, mortality-enhancing effects of long-term UPF consumption. Study findings revealed that females and older individuals were at heightened mortality risk compared to their younger or male counterparts. Patients with higher BMIs and those who have never smoked were at similarly exacerbated risk.

Lipid and lipoprotein analysis supported these findings, revealing that higher UPF intake was linked to unfavorable lipid profiles, including reduced HDL and increased VLDL. Metabolomic analyses validated these findings while further identifying 93 metabolic signatures that can be used to quantify physiological UPF exposure in future research.

Together, these findings substantiate global public health campaigns against the excessive consumption of UPFs and inform consumers of the potential self-harm their purchase and intake are causing.

Journal reference:

• Du, Y., Zhang, S., Schjølberg, J. S., Hadden, D., Smith, J. G., Qi, L., Sonestedt, E., & Borné, Y. (2024). Ultra-processed food consumption, plasma metabolite profile, and risk of all-cause and cause-specific mortality in a population-based cohort. In Clinical Nutrition. Elsevier BV, DOI – 10.1016/j.clnu.2024.10.023, https://www.sciencedirect.com/science/article/pii/S0261561424003807