Ultra-processed foods leave behind metabolic “signature” in blood, study finds

Ultra-processed food (UPF) consumption leaves behind a distinct metabolic “signature” in the blood, associated with potentially adverse health conditions, according to findings from a new internationally led study. 

To learn more, Nutrition Insight speaks to study co-author Jessica Blanco-López, Ph.D., head of the Research Department at the School of Medicine, Universidad Francisco Marroquín, Guatemala. She has a background in pediatrics and oncology, which led her to become involved in studies related to nutrition and metabolism.

The trial is the first to use targeted metabolomics — the scientific study of the chemical processes involved in cell metabolism — to examine the effects of UPF intake on a large European cohort. It underscores the potential metabolic impact of UPFs and highlights the need for further research to clarify the biological pathways linking food processing with chronic diseases and mortality.

“From a research perspective, the fatty acid profile [of a UPF] may be particularly informative,” Blanco-López tells us. “We observed lower levels of potentially beneficial fatty acids, such as docosahexaenoic acid (DHA), together with higher levels of industrial trans fatty acids, saturated fatty acids, and several omega-6 fatty acid derivatives.”

Elaidic acid, an industrial trans fatty acid, is especially relevant in this context, as it has previously been used as a marker of industrial food processing. “In addition, metabolites involved in lipid and energy metabolism, including acylcarnitines, glycerophospholipids, and sphingomyelins, may help us better understand how UPF consumption relates to metabolic health,” Blanco-López notes.

“However, these biomarkers are not yet ready to be used as diagnostic tools or as the basis for product-level health claims; they first need replication and validation in different populations and study designs.”

Metabolic pathways linking UPFs to poor health

The peer-reviewed paper, published in the journal Critical Reviews in Food Science and Nutrition, explores potential metabolic pathways linking UPF to poor health.

While emerging evidence links consumption of UPF to higher risks of cancer, cardiovascular disease, type 2 diabetes, obesity, and mortality, researchers note that the biological explanations for this remain unclear.

Higher UPF consumption is linked to increased biomarkers of mitochondrial dysfunction and fewer essential lipids needed for cell membrane stability and signalling.

Blanco-Lopez and her colleagues identified molecular signatures of UPF intake using data from 15,200 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

The team questioned participants about their diet and classified the results using the Nova system, which categorizes foods into four groups, from unprocessed to ultra-processed.

They also measured levels of metabolites — an intermediate or end product of metabolism — and fatty acids in blood samples taken from the participants.

Next, they used regression modeling to identify metabolite and fatty acid “signatures” associated with UPF consumption while taking into account participants’ demographic, lifestyle, and other confounding factors.

UPF intake was found to be associated with 22 circulating metabolites. Higher UPF consumption was associated with a higher occurrence of certain lipid derivatives that are biomarkers of impaired fatty acid oxidation and mitochondrial dysfunction, and a lower occurrence of several other lipids that are essential for cell membrane stability, permeability, and cell signaling.

This metabolic signature suggests that UPF consumption may stimulate the synthesis of endogenous lipids (fatty compounds, such as cholesterol) and inhibit healthy lipid processing.

Fatty acid patterns

UPF intake was also associated with eight plasma fatty acids. Higher UPF consumption resulted in a pattern of high stearic acid levels (which indicate high saturated fat intake or metabolic issues) alongside high levels of long-chain polyunsaturated fatty acids.

This suggests the metabolic impact of UPFs extends beyond their fat content to stimulate internal lipid synthesis from excess dietary carbohydrates. According to the researchers, this association further confirms that even low levels of industrial fatty exposure persist in the blood circulation.

The findings suggest that ultra-processed foods trigger the body to turn extra carbohydrates into fat, while also showing that even small amounts of industrial fats stay in your bloodstream for a long time.Blanco-Lopez notes that this finding may have several implications. She explains that the simultaneous decline in protective fatty acids and the increase in metabolic stress suggest that UPF consumption may contribute to health risks through nutritional displacement and inducing metabolic disruption.

“Our findings suggest that the metabolic impact of UPFs may not be explained solely by the amount or type of fat they contain,” she notes.

“Future research should examine the overall food matrix and formulation more closely, including refined carbohydrates, added sugars, industrial fats, emulsifiers, additives, and the displacement of nutrient-rich foods such as fish, dairy products, legumes, whole grains, fruits, and vegetables,” she highlights.

“The combination of high energy density, low micronutrient density, and industrial processing may influence lipid metabolism in ways not captured by traditional nutrient labels alone.”

Beyond nutrient profiling

Blanco-López further reflects on how metabolomics could help nutrition companies move beyond traditional nutrient profiling when developing healthier processed foods or functional ingredients.

“Metabolomics can provide a more comprehensive picture of how foods are reflected in human biology,” she notes. “Traditional nutrient profiling usually focuses on nutrients such as fat, sugar, salt, fiber, and calories. These are important, but they may not fully capture how a food affects metabolic pathways after consumption.”

She adds that metabolomics is helpful in identifying biological responses related to lipid metabolism, energy metabolism, inflammation, or other pathways, and may eventually support the development of healthier processed foods.

“However, this should be seen as a research tool at this stage. Before metabolomic signatures can guide product development or claims, they need to be validated against meaningful health outcomes.”

Study limitations

One limitation of the paper flagged by the research team is that the study observed people at one point in time rather than following them over many years. Because of this, they cannot definitively say that eating UPFs causes the metabolic changes they found.

A limitation of the study is its one-time observation of participants, meaning it cannot definitively prove that eating UPFs causes these metabolic changes.

The study also does not specify any types of UPFs or ingredients that appeared to contribute more strongly to the metabolic signature.

“This is something future studies need to clarify,” Blanco-López tells us. “In our study, we examined overall UPF consumption using the Nova classification, rather than isolating specific products, brands, ingredients, or additives.”

“The dietary questionnaires used in EPIC were not originally designed to capture detailed information on food processing, so we cannot conclude from these data which specific UPF categories or ingredients were the main drivers of the metabolic signature.”

She stresses that future studies with more detailed dietary assessment, brand-level information, and, ideally, controlled feeding designs will be important to answer this question.

“The next priorities are replication in other populations, longitudinal studies to test whether these signatures predict future disease risk, and controlled feeding trials to determine whether ultra-processed foods directly induce these metabolic changes,” she highlights.

It will also be important to integrate metabolomics with other biological markers, such as inflammatory markers and the gut microbiome, to better understand the mechanisms.

“In the longer term, validated metabolic signatures could help refine dietary recommendations by moving beyond broad food categories toward a better understanding of biological impact,” says Blanco-López. “However, for health claims or product-level recommendations, much stronger causal evidence would be needed.”