A clinical trial that provides important evidence on yerba mate's cardiovascular health effects has been retrospectively registered on ClinicalTrials.gov — nearly a decade after its completion. The INFU-SALUD study (NCT06729905), conducted at the Institute of Food Science, Technology and Nutrition (ICTAN-CSIC) in Madrid, Spain, ran from January 2012 to May 2015 [1]. Its results were published in Molecular Nutrition & Food Research in April 2025 [3]. The study was designed as a randomized, crossover, controlled trial — the gold-standard design for evaluating dietary interventions — and enrolled 52 participants: both healthy volunteers and individuals with mildly elevated cholesterol.
The Trial Design
INFU-SALUD used a crossover design, meaning each participant served as their own control. After a two-week run-in period, participants consumed three cups of yerba mate tea daily for eight weeks, then underwent a three-week washout, followed by eight weeks of a control drink (water or isotonic drink, free of polyphenols and caffeine) — or vice versa, depending on randomization [1]. The total intervention period was approximately five months. Blood samples were collected at the beginning and end of each eight-week period. The primary outcome was the effect on blood lipid levels — total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and phospholipids. Secondary outcomes included blood pressure, fasting glucose and insulin, inflammatory cytokines (including TNF-α, IL-6, CRP, and others), hormones and incretins (including GLP-1, ghrelin, and leptin), and anthropometric measurements.
Who Participated
Importantly, the study population was not what would be described clinically as 'high-risk cardiovascular patients.' The trial accepted healthy volunteers and included two groups: a healthy group (total cholesterol below 200 mg/dL or LDL below 130 mg/dL) and a group described as 'at cardiovascular risk' (total cholesterol 200–240 mg/dL or LDL 130–159 mg/dL) [1]. All participants were required to have a normal BMI of 20–25 kg/m². Smokers, vegans and vegetarians, people taking statins or other prescription drugs, and those with chronic diseases beyond mild hypercholesterolemia were excluded. In clinical terms, these were lean, otherwise-healthy adults — some with borderline-elevated cholesterol. The trial enrolled 52 participants [1].
The Retrospective Registration
A notable aspect of INFU-SALUD is its registration timeline. Although the study started in January 2012 and completed in May 2015, it was first posted to ClinicalTrials.gov on December 12, 2024 — nearly a decade after completion [1]. Retrospective registration is not uncommon in nutrition research, particularly for trials that predate the widespread adoption of mandatory prospective registration. However, it is a significant methodological limitation: prospective registration (before enrollment begins) is considered best practice because it prevents selective outcome reporting and publication bias. The results were published in 2025 by Bravo et al. in Molecular Nutrition & Food Research, suggesting the researchers registered the trial when preparing the publication [3].
Context: The Current Evidence Base
The existing evidence on yerba mate and cardiovascular biomarkers is fragmented and, in some cases, contradictory. The 2025 Frontiers in Endocrinology meta-analysis of 13 randomized controlled trials [2] found significant improvements in glycemic markers (postprandial glucose, HbA1c, HOMA index) in pre-diabetic patients, but no significant effects on lipid parameters — total cholesterol, LDL-cholesterol, HDL-cholesterol, or triglycerides. Some individual trials have reported lipid-lowering effects, particularly for LDL-cholesterol, but these findings have not been consistent across studies. INFU-SALUD's published results may help clarify this picture, particularly for populations with mildly elevated cholesterol.
Regulatory Landscape
For the yerba mate industry, clinical trials like INFU-SALUD are important stepping stones toward regulatory recognition of health benefits. In the European Union, the framework for substantiating health claims is governed by Regulation (EC) No 1924/2006, under which the European Food Safety Authority (EFSA) evaluates the scientific evidence and the EU institutions decide on authorisation. In the United States, the FDA's qualified health claim framework allows companies to petitions for claims supported by credible but not conclusive evidence. Currently, no yerba mate product carries an authorised or qualified health claim in either market. A single trial — even a well-designed one — is typically insufficient for regulatory approval; authorities generally require a body of evidence from multiple independent trials. Nevertheless, each rigorous study like INFU-SALUD adds to the evidence base that could eventually support such submissions.
It is worth noting what INFU-SALUD, as a single trial, cannot resolve: the question of optimal dose, preparation method, and duration of yerba mate consumption for cardiovascular benefit. The trial used a specific regimen of three cups of brewed yerba mate tea per day in lean, nonhabitual consumers, which may or may not generalize to the RTD products, loose-leaf preparations, and concentrated extracts that constitute the diverse global yerba mate market. Nevertheless, the study represents a methodological contribution — a controlled, registered clinical trial with published results, conducted with appropriate blinding and crossover design.