The clinical study protocol, titled "Biological Effects of Consuming Limosilactobacillus fermentum CRL 1446 CONICET in Volunteers with Cardiovascular Risk Factors" was issued in October 2025 in Version 3.
Rationale and Theoretical Background
The protocol is underpinned by the acknowledgment of the **key influence of the gut microbiota** on human health, especially concerning cardiovascular risk factors. Data from Argentina's Fourth National Risk Factor Survey indicates a rise in overweight and obesity from 49% in 2005 to 61.6% in 2018. Overweight and obesity, along with dyslipidemia, hypertension, insulin resistance, and chronic inflammation, are closely correlated with imbalances in the gut microbiota, known as dysbiosis, which elevates the risk of cardiovascular diseases. Dysbiosis is characterized by a reduction in bacterial diversity, an increase in pro-inflammatory bacteria, and a decrease in beneficial bacteria that produce short-chain fatty acids.
Nutritional intervention utilizing probiotics presents a promising alternative for modulating the gut microbiota's composition and function, thereby improving major cardiovascular risk factors. A probiotic is defined by FAO/WHO as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host".
The specific strain under investigation, **Limosilactobacillus fermentum CRL 1446**, demonstrates a singular combination of functional mechanisms that support its potential efficacy in individuals with cardiovascular risk factors. Preclinical assays have shown that administration of the feruloyl esterase-producing strain L. fermentum CRL1446 improves metabolic and oxidative parameters. It is capable of modulating the gut microbiota through the production of beneficial metabolites, enhancing the integrity of the intestinal barrier and reducing bacterial translocation. Furthermore, this strain positively affects lipid metabolism by regulating key enzymes involved in lipid synthesis and degradation. It also exhibits an immunomodulatory action observed in preclinical trials, promoting an anti-inflammatory profile by stimulating regulatory cytokines and decreasing pro-inflammatory mediators. The strain's dual anti-inflammatory and antioxidant effect is linked to an increase in endogenous antioxidant enzymes like superoxide dismutase and glutathione peroxidase, suggesting a capacity to counteract cellular oxidative damage and potentially preserve endothelial function.
Research Question and Hypothesis
The primary research question is whether the consumption of L. fermentum CRL1446 can induce improvements in the metabolic health of adult volunteers with cardiovascular risk factors, potentially preventing or mitigating non-communicable chronic diseases. The working hypothesis is that volunteers who consume L. fermentum CRL 1446 will exhibit significant improvements in their metabolic health compared to those who do not.
Objectives
The **general objective** is to assess the efficacy of the L. fermentum CRL1446 strain in preventing postprandial glucose peaks, modulating intracellular and plasma inflammatory and redox status, and altering body composition, in volunteers receiving both acute (up to 30 days) and chronic (from 90 days) nutritional interventions.
**Specific objectives** include:
- Evaluating gastrointestinal symptomatology using the GSRS scale in 80 volunteers during the acute and chronic intervention phases.
- Evaluating postprandial glucose absorption levels and body composition changes in 30 volunteers before and after of consuming 1 capsule/day and 2 capsules/day of L. fermentum CRL1446, compared to placebo. Acute intervention phase.
- Evaluating postprandial glucose absorption levels and body composition changes in 50 volunteers before and after of consuming 1 capsule/day and 2 capsules/day of L. fermentum CRL1446, compared to placebo. Chronic intervention phase.
- Evaluating the modification of biomarkers for oxidative stress, antioxidant defenses, DNA damage, and chronic inflammation in 50 volunteers before and after of consumption (1 capsule/day and 2 capsules/day), compared to placebo. Chronic intervention phase.
