A tightly controlled clinical trial reveals that ultra-processed foods not only drive weight gain and worsen cholesterol levels but also impact reproductive hormones and sperm health, highlighting harms that extend beyond calories alone.

Study: Effect of ultra-processed food consumption on male reproductive and metabolic health. Image Credit: Rimma Bondarenko / Shutterstock
In a recent article in the journal Cell Metabolism, researchers conducted a randomized controlled trial (RCT) to investigate whether ultra-processed foods (UPFs) harm reproductive and metabolic health. They found that UPF-rich diets increased unhealthy cholesterol levels, fat mass, and body weight. These diets also altered hormones related to reproduction and metabolism. Sperm motility showed a non-significant downward trend after multiple-testing correction compared with unprocessed diets.
UPFs have become a significant part of diets worldwide, accounting for more than half of daily energy intake in countries such as Canada, Australia, the UK, and the USA.
These foods, classified as NOVA category 4, are made from highly processed or synthetic ingredients. They are high in added sugars, saturated fats, and refined carbohydrates, but low in fiber. Beyond poor nutritional value, UPFs may expose consumers to contaminants like phthalates. These can leach from packaging or processing, disrupt hormonal balance, and potentially harm reproductive and metabolic functions.
Epidemiological studies link UPF consumption with obesity, cardiovascular disease, diabetes, cancer, and mental health problems. While prior research has examined cardiometabolic outcomes, far fewer studies have explored reproductive effects.
There is evidence of a global decline in sperm count, around 60% since the 1970s. Factors such as higher body weight, poor dietary fat intake, and exposure to endocrine-disrupting chemicals may contribute. UPFs are likely to play a role.
Previous randomized trials have confirmed that UPFs increase calorie intake by 500–800 kcal/day compared to unprocessed diets; however, it remains unclear whether adverse outcomes result from excess calories alone or the inherent properties of UPFs.
About the study
In this study, researchers directly compared unprocessed and UPF diets at both adequate and excess calorie levels. They recruited 43 men to participate in a dual-arm, 2 × 2 crossover study with a 12-week washout period.
Each participant received both an unprocessed and a UPF-rich diet for 3 weeks at either a calorically adequate or excess level, with the diet order randomized. Both diets were similar in macronutrient composition, but UPFs contained more saturated fat, cholesterol, refined grains, and sugar, and less fiber. After seven study visits, participants underwent anthropometrics, Dual-Energy X-ray Absorptiometry (DXA) scans, blood draws, and semen collection.
Semen quality was assessed within 90 minutes, while blood and plasma were analyzed for biochemical, hormonal, inflammatory, and pollutant markers using standardized assays and mass spectrometry. Data were evaluated with mixed linear models that adjusted for diet order and multiple testing.
Key findings
The UPF diet resulted in significant weight gain (approximately 1.3–1.4 kg) and an increase in fat mass (approximately 1 kg) in both calorie arms, primarily due to weight loss during the unprocessed diet.
Cholesterol levels and the ratio of low-density lipoprotein (LDL) to high-density lipoprotein (HDL) rose with UPF intake, in the adequate-calorie arm only, while diastolic blood pressure increased in the excess-calorie arm only.
Hormonal changes included lower growth/differentiation factor 15 (GDF-15) and a trend toward higher leptin in the excess-calorie arm, and T3 and TSH trends upward in the adequate-calorie arm. Reproductive effects were notable, with the follicle-stimulating hormone (FSH) decreasing in the excess calorie arm and testosterone showing a downward trend in the adequate arm, while sperm motility tended to decline but was not statistically significant.
Exposure to environmental pollutants also shifted in relation to diet. UPF intake decreased lithium and mercury in blood and semen, while slightly raising serum levels of a phthalate metabolite (cxMINP). Both experimental diets were cleaner than participants’ habitual diets, leading to lower overall pollutant exposure, though UPFs still introduced specific harmful compounds.
Mental health markers were essentially unchanged, though depression scores trended upward with UPFs.
Inflammatory markers showed minor shifts, with relative to baseline, the unprocessed diet showing a transient pro-inflammatory signature in lean participants (higher IFN-γ and CRP, lower IL-4); however, versus UPF, the unprocessed diet increased IL-4 and tended to reduce MCP-1, while CRP was unchanged.
Conclusions
This trial showed that UPFs negatively affect cardiometabolic and reproductive health, even when calorie intake is controlled. Participants consuming UPFs gained more weight and fat mass, had higher LDL:HDL cholesterol ratios, and showed hormonal shifts linked to energy balance and reproduction, including reduced FSH and altered GDF-15.
Importantly, these effects were not fully explained by calorie load, suggesting that calories from UPFs and unprocessed foods are metabolized differently.
Trends in pollutant accumulation were also observed, with increased levels of certain phthalates after UPF intake, which may contribute to cardiovascular, reproductive, and mood-related effects.
This report presents secondary outcomes only; the trial’s primary endpoint (sperm DNA methylation) will be reported separately.
Overall, the study supports reducing UPF consumption to promote metabolic, reproductive, and mental health. However, limitations include reliance on self-reported adherence, a relatively short intervention period, and possible transient effects that may differ with longer-term diets.
Journal reference:
- Effect of ultra-processed food consumption on male reproductive and metabolic health. Preston, J.M., Iversen, J., Hufnagel, A., Hjort, L., Taylor, J., Sanchez, C., George, V., Hansen, A.N., Ängquist, L., Hermann, S., Craig, J.M., Torekov, S., Lindh, C., Hougaard, K.S., Nóbrega, M.A., Simpson, S.J., Barrès, R. Cell Metabolism (2025). DOI: 10.1016/j.cmet.2025.08.004, https://www.cell.com/cell-metabolism/fulltext/S1550-4131%2825%2900360-2