The more ultra-processed foods on your plate, the higher your risk of gallstones.

A prospective study of over 120,000 adults published in Current Developments in Nutrition found that the higher the proportion of ultra-processed foods (UPF) in the diet, the higher the risk of first-time gallstone disease. This is not about a “one-time snack,” but about a long-term dietary habit: the authors assessed the usual diet and tracked incident cases of cholelithiasis. The conclusion is consistent with earlier independent data and strengthens the signal for certain UPF categories — primarily sugary and “diet” drinks.

Background

• What is UPF and why is it controversial? The NOVA concept divides foods by the degree and purpose of industrial processing: ultra-processed are formulas of processed ingredients and additives (emulsifiers, sweeteners, flavors) created for convenience and “hyperpalatability.” The approach is widely used in research, but is criticized for its blurred boundaries and “technological heterogeneity” within groups — that is, NOVA is useful as an epidemiological marker, but not an ideal technical term.
• What large cohorts have already shown. In 2024, an analysis of three prospective US cohorts showed that each additional UPF serving per day was associated with a ≈2.8% higher risk of new-onset gallstone disease; the largest contribution came from sugary and “diet” drinks. Some of the effect in young women was mediated by obesity, but the association did not completely disappear after adjustment. The new CDN paper expands on this signal and confirms it in an independent sample.
• Why it is biologically plausible (pathogenesis of stones). Stones are most often cholesterol stones and form in three steps: supersaturation of bile with cholesterol, nucleation of crystals and their retention in the hypomotility of the gallbladder. These links are affected by insulin resistance, dyslipidemia, inflammation and slow motility - exactly what UPF diets are most often associated with.
• Role of beverages and supplements. Frequent consumption of sugary/sweetened beverages is associated with weight gain, NAFLD, and altered lipid profiles that increase bile cholesterol saturation. The contribution of emulsifiers (carboxymethylcellulose, polysorbate-80) is also discussed: they can alter the microbiota, increase intestinal permeability, and increase low-level inflammation, an indirect pathway to metabolic disorders and hypomotility. There is less direct clinical data on the gallbladder, but the mechanistic trend is stable.
• Classic risk factors for gallstones that should not be forgotten. Unmodifiable: female gender, age, some ethnic groups. Modifiable: obesity, especially abdominal; low physical activity; rapid weight loss (including VLCD and bariatrics). Therefore, part of the “UPF → stones” relationship goes through body weight and behavioral patterns, which requires careful adjustments in the analyses.
• Why more data is needed. The NOVA classification of UPF is an observational study; it captures associations, not causation. To understand the contribution of specific mechanisms (sweeteners, emulsifiers, fiber deficiency, etc.), intervention and mediator studies are needed: what happens to risk and bile biomarkers if the proportion of UPF (or individual subtypes) is deliberately reduced while maintaining caloric content and weight.

What did they do?

• Design: Prospective cohort (≈122,431 participants): dietary data (focusing on UPF proportion using the NOVA system) were collected at baseline, and first cholelithiasis diagnoses were recorded during follow-up. The risk model was adjusted for key factors (age, gender, smoking, physical activity, body weight, etc.).
• The big question is: Is there a dose-dependent relationship between the proportion of UPF in the diet and the risk of gallstones/gallbladders? And which UPF subtypes contribute the most?

Results

• People whose diets contained more ultra-processed foods had a higher risk of newly diagnosed cholelithiasis compared with those who ate UPF less often. The association remained after adjusting for habitual risk factors.
• The most “problematic” categories have traditionally been sugary drinks (including sugar-sweetened and artificially sweetened drinks) – this is consistent with a large analysis of three cohorts, where each additional UPF serving per day was associated with a ≈2.8% increase in gallstone risk, with beverages making the largest contribution.
• Part of the association may be mediated by obesity (especially in younger women), but even after controlling for body weight, the signal does not completely disappear, suggesting that additional mechanisms are at work. These observations echo previous work.

Why might this be?

• Sugar/sweetener metabolism. Frequent consumption of sugary and “diet” drinks is associated with insulin resistance, dyslipidemia, and fatty liver disease, factors that increase bile cholesterol saturation and the tendency to stone formation.
• Additives and product matrix. UPF is characterized by emulsifiers, stabilizers, texturizers, which can change the motility of the gallbladder, microbiota and the intestinal-hepatic cycle of bile acids. Evidence for individual additives is still fragmentary, but this direction is being actively studied.
• General “dietary ecology.” Diets with a high UPF content are usually poorer in fiber and micronutrients, and are more often accompanied by excess weight, physical inactivity, and sleep disturbances—all independent predictors of stone formation.

What does it mean "for life"

• Reducing the UPF share is a reasonable preventative goal. The easiest place to start is with drinks: replace sugary/"diet" sodas and energy drinks with water, unsweetened tea/coffee. This makes a quick contribution to reducing the UPF "pool".
• Create a “minimally processed” diet. Base your menu on whole foods (vegetables, fruits, legumes, whole grains, fish/eggs/dairy, nuts, seeds). UPF is not “taboo,” but let them be rare guests, not 50-60% of calories.
• Monitor your weight and exercise. Weight gain/loss and obesity are strong risk factors for stones; a gentle, sustained calorie deficit and physical activity help both directly and by reducing UPF cravings.

Does this fit into the scientific picture?

Yes. In 2024, the AJCN showed an association of UPF with gallstone risk in three large cohorts; the new CDN paper confirms and extends this signal in an independent population with a different design and a focus on “incident” cases. Taken together, the data strengthen the causal hypothesis, although only intervention studies can definitively prove causality.

Restrictions

• Observational design. It shows association, not proven causation; there may be residual confounding (lifestyle, access to medicine, etc.).
• The UPF (NOVA) classification is a subject of debate: the boundaries are sometimes blurred and the food questionnaires are not perfect. However, when different cohorts and methods give similar results, the credibility of the signal increases.

Sources:

• Ultra-Processed Food Consumption and Cholelithiasis —Current Developments in Nutrition, 2025 (full text/abstract).
• “Ultraprocessed food consumption and risk of gallstone disease: analysis of 3 prospective cohorts” - American Journal of Clinical Nutrition, 2024