Meta-analysis links UPF intake to disease risk, but experts question certainty

A new analysis links higher ultra-processed food (UPF) intake to a greater risk of mortality and major chronic health issues, including digestive diseases, high blood pressure, and metabolic syndrome or diabetes. The findings suggest that every extra 100 g of UPFs consumed corresponds to greater risks. 

The study defines UPFs as ready-to-eat or heat-and-serve products manufactured through extensive industrial processing. It notes that these usually contain a range of additives and are energy-dense while being high in sugar and salt. They are also typically lower in dietary fiber, protein, vitamins, and minerals, explain the authors.

Several compounds that may form during food processing have been associated with a higher incidence of cardiovascular disease, they add. These include acrylamide, a contaminant formed in heat-treated processed foods, and acrolein, which is generated during fat heating.

The review highlights emerging evidence suggesting that the combination of multiple additives may exert a “cocktail effect” on human health. The researchers note that laboratory studies included in the analysis have shown that UPFs may adversely affect the gut microbiome, and promote inflammation and insulin resistance.

However, independent experts critiquing the paper findings urge caution when interpreting these results.

“While these kinds of studies are meant to provide the highest level of evidence by pooling research, the results can only be as good as the underlying research,” says Gunter Kuhnle, professor of Nutrition and Food Science at the University of Reading, UK.

Pooled data analysis

In the paper in Family Medicine and Community Health researchers pooled data analysis of published evidence. Spanning trials from the Americas, Europe, Asia, and Oceania, the studies involved a collective 8,819,894 adult participants. Monitoring periods took place over two to 32 years.

Researchers across the included studies assessed UPF consumption using food frequency questionnaires, 24-hour dietary recalls, or dietary histories. To evaluate the health impact of this exposure, the authors converted daily UPF intake into 50 g serving increments, expressing the primary dose-response risk per 100 g/day increase.

Commenting on the study method, Kuhnle from the University of Reading argues that measuring food intake this way relies on “very unreliable data,” as dietary assessments rarely capture the nuances required to define UPFs correctly.

“Most dietary assessment methods do not collect sufficient data to categorize foods reliably; for example, artisan bread is not UPF, while supermarket-bought bread generally is — but many assessment methods simply record ‘bread,’” he explains.

Associated health outcomes

The analysis authors analyzed specific health outcomes, including high blood pressure and cardiovascular events such as heart attack, stroke, transient ischemic attacks or “mini strokes,” coronary artery disease, and cardiovascular death.

They also examined records of cancer events, metabolic syndrome or diabetes, digestive diseases, obesity or overweight, depression or anxiety, and death from any cause.

Pooled data analysis of the results of the included studies reveals that higher UPF consumption was associated with greater risks of multiple chronic health issues and death from any cause. The authors note these risks rose in tandem with the quantity consumed.

More specifically, the study linked people with the highest intake of UPFs with higher relative risks of cardiovascular events (24% higher risk), cancer (12%), obesity or overweight (23%), metabolic syndrome/diabetes (24%), depression/anxiety (27%), digestive diseases (31%), high blood pressure (11%), and death from any cause (18%).

Additional analyses demonstrated that each additional 100 g/day consumed was associated with greater risks of cardiovascular events (14%), cancer (4%), death from any cause (3%), and metabolic syndrome or diabetes (2%).

Moreover, every 10% increase in weight or energy intake was associated with a 16% greater risk of metabolic syndrome or diabetes.

“Given that UPF-related chronic diseases often cluster as multimorbidity, reducing consumption of UPFs and replacing them with minimally processed alternatives may be relevant for chronic disease prevention and primary care management,” the researchers conclude.

Further critiques of the findings

The meta-analysis authors recognize limitations to their findings, including that all the included studies relied on subjective dietary assessments and excluded participants under the age of 18.

They also recognize that UPF consumption often happens in the context of broader lifestyle and behavioral patterns that are difficult to fully adjust for and that may influence long-term health risks, as well as mortality.

Socioeconomic status remains a critical unadjusted factor, according to Dr. Adam Jacobs, an external commentator working as an executive director in Biostatistics at Ergomed. He says that poverty is one of the strongest predictors of poor health, and low UPF consumption often correlates with wealth.

“It is possible that UPF consumption is simply a marker for poverty, rather than being harmful per se,” he notes.

He adds that only 19 of the 51 studies adjusted for economic measures and that the review authors “assessed only one of their outcomes (obesity and overweight) as having moderate certainty: the other seven were all rated as either low or very low certainty.”

Jacobs also claims that the review failed to assess publication bias, noting: “Overall, because of the risk of residual confounding and publication bias, I do not find Liu et al.’s conclusions compelling.”