In two large prospective cohorts with up to 34 years of follow-up, we found that higher consumption of ultra-processed foods was associated with modestly higher all cause mortality. We found no associations for mortality due to cancer or cardiovascular diseases. The associations varied across subgroups of ultra-processed foods, with meat/poultry/seafood based ready-to-eat products consistently showing associations with higher all cause mortality and cause specific mortality. The associations between ultra-processed food consumption and mortality were attenuated after we accounted for overall dietary quality.
Comparison with other studies and possible explanations
Existing evidence suggests a relation between ultra-processed food consumption and mortality. A meta-analysis of prospective cohorts reported that the highest ultra-processed food consumption was associated with higher all cause mortality compared with the lowest consumption (hazard ratio 1.21, 1.13 to 1.30).23 Two studies were conducted in the US,2425 whereas the other six were conducted in Spain,262728 France,29 Italy,30 and the UK.31 Unlike our study, which excluded alcohol from ultra-processed foods and carefully controlled for smoking status and pack years, all the above studies included alcohol in ultra-processed foods and adjusted for smoking status (never, former, and current) only. As noted in our sensitivity analysis, pack years of smoking strongly confounded the association—additionally adjusting for smoking pack years remarkably attenuated the hazard ratios toward the null. That may partly explain why the associations found in our study were weaker than those in previous studies. Another possible reason could be tighter control for socioeconomic status because our participants were all health professionals and had similar levels of education.
The evidence on mortality due to cancer is relatively sparse. Consistently, the Moli-sani Study did not observe a statistically significant association but reported a positive association with other mortality.30 An analysis of three cohorts including the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), NHANES (1999-2018), and UK Biobank reported null findings for mortality due to cancer in the PLCO and NHANES (1999-2018).32 By contrast, the UK Biobank study found that every 10% increment in ultra-processed food consumption was associated with a 6% higher cancer mortality.33 Diet was assessed in the UK Biobank through multiple 24 hour recalls between 2009 and 2012, and 40% of the participants had only one 24 hour recall, thus limiting the ability to capture long term dietary intake.
In agreement with our study, the Prospective Urban and Rural Epidemiology study from 25 high income, middle income, and low income countries in America, Europe, Africa, and Asia observed a null association with mortality due to cardiovascular diseases but a positive association with non-cardiovascular disease mortality.34 Our findings on the relation between ultra-processed foods and mortality due to cardiovascular diseases are inconsistent with previous evidence from Europe but consistent with the null finding in the US NHANES III (1988-94).242530 Moreover, a much stronger positive association was reported in the UK Biobank (1.28, 1.13 to 1.45) compared with the two US cohorts (1.12, 1.05 to 1.09; 1.11, 0.92 to 1.34).32 In addition to the methodological differences mentioned above, different study populations, ultra-processed food compositions, and eating patterns may also contribute. Ultra-processed food intake in our two US cohorts is mainly contributed by “sauces, spreads, and condiments” and “sweet snacks and desserts,” which together accounted for nearly 50% (supplementary figure B), but neither of the two subgroups was associated with increased mortality due to cardiovascular diseases. On the other hand, compelling evidence shows that nuts and (dark) chocolate, common constituents of “sweet snacks and desserts,” are inversely associated with cardiovascular diseases.3536 We observed that dark chocolate in the subgroup “packaged sweet snacks and desserts” was associated with decreased mortality (supplementary table D). Therefore, the diverse array of constituents contained in ultra-processed foods with heterogeneous health effects may have contributed to the discrepant findings. Our findings suggest that meat/poultry/seafood based ready-to-eat products and sugar sweetened and artificially sweetened beverages are major factors contributing to the harmful influence of ultra-processed foods on mortality, which is in accordance with previous studies.13373839
Few studies have investigated the relation with cause specific mortality other than that due to cancer and cardiovascular diseases. We found that ultra-processed food intake was associated with higher neurodegenerative mortality. Increasing evidence suggests that ultra-processed food is linked to higher risk of central nervous system demyelination (a precursor of multiple sclerosis),40 lower cognitive function,41 and dementia.42 Studies have shown that a diet rich in ultra-processed foods may drive neuroinflammation and impairment of the blood-brain barrier, leading to neurodegeneration.4344 Of note, among ultra-processed food subgroups, diary based desserts showed the strongest association with neurodegenerative mortality. Earlier finding from the HPFS and NHS cohorts showed that intake of sherbet/frozen yogurt was associated with an increased risk of Parkinson’s disease.45 Furthermore, we found a positive association between ultra-processed food intake measured by percentage of energy and respiratory mortality. Emerging evidence suggests that higher ultra-processed food intake is associated with increased risk of respiratory multimorbidity.46 The increased respiratory mortality associated with processed red meat may be partly due to heme iron and nitrate/nitrite.47
An important question not answered by previous studies is whether and how food processing level and nutritional quality jointly influence health. We observed that in the joint analysis, the AHEI score but not ultra-processed food intake showed a consistent association with mortality and that further adjustment for the AHEI score attenuated the association of ultra-processed food intake with mortality. Although including AHEI in the multivariable model for ultra-processed food may represent an overadjustment because common foods are included in both the AHEI and ultra-processed food, our data together suggest that dietary quality has a predominant influence on long term health, whereas the additional effect of food processing is likely to be limited. Furthermore, foods may have dual attributes according to their processing level and nutritional quality, and these two features may have quantitatively and even qualitatively different effects on health. Another added value of our study is the exclusion of wholegrain products that fall in the ultra-processed foods from the primary exposure, based on the well established health benefits associated with whole grains. By taking this approach, we aim to rectify the potential misperception that all ultra-processed food products should be universally restricted and to avoid oversimplification when formulating dietary recommendations.
Besides neglecting overall nutritional quality, the ultra-processed food classification system has other limitations. The Nova classification is based on broad categories that do not capture the full complexity of food processing,48 leading to potential misclassification. Further work is needed to improve the assessment and categorization of ultra-processed foods. On the other hand, dietary guidelines should provide clear and sound food selections that are available, actionable, attainable, and affordable for the largest proportion of the population. Thus, careful deliberation is necessary when considering incorporation of ultra-processed foods into dietary guidelines.4950 Again, on the basis of our data, limiting total ultra-processed food consumption may not have a substantial influence on premature death, whereas reducing consumption of certain ultra-processed food subgroups (for example, processed meat) can be beneficial.
We note that mortality is a more complicated endpoint than disease incidence and is also influenced by several factors including early detection, treatment, and individuals’ overall health status. The findings for mortality should not be regarded as synonymous with those pertaining to disease incidence but rather considered as more comprehensive assessment of the health impact of risk factors.