Integrated safety and microbiota profiling of fulvic acid formulations across in vitro and in vivo models.

Both fossil-based fulvic acid formulations (MLG-50 and MLG-A50) demonstrated high cytocompatibility across a broad concentration range in multiple eukaryotic cell models.

• Cytocompatibility was assessed in L929 fibroblasts, LoVo epithelial cells, and HepG2 hepatocytes.
• Both MLG-50 and alkaline MLG-A50 formulations were evaluated across a broad concentration range.
• High cytocompatibility was observed across all tested cell lines.
• No relevant nuclear abnormalities were detected in the tested formulations.

Genotoxicity levels induced by both fulvic acid formulations were significantly lower than those induced by reference dietary compounds.

• Genotoxicity was assessed in eukaryotic cell models including L929 fibroblasts, LoVo epithelial cells, and HepG2 hepatocytes.
• Genotoxicity of MLG-50 and MLG-A50 was compared against reference dietary compounds.
• No relevant nuclear abnormalities were detected for either formulation.
• Results were characterized as 'significantly lower than those induced by reference dietary compounds.'

Cell proliferation assays revealed enhanced intestinal epithelial cell growth at sub-toxic concentrations of the fulvic acid formulations.

• Proliferation enhancement was observed in intestinal epithelial cells (LoVo cell line).
• The effect was observed specifically at sub-toxic concentrations.
• This finding suggests a potential regenerative or growth-supportive role for fulvic acid formulations.

MLG-A50 demonstrated a pro-regenerative effect in LoVo intestinal epithelial cells as measured by wound healing assays.

• Wound healing assays were performed in LoVo epithelial cells.
• MLG-A50 showed an increased wound closure rate compared with the untreated control.
• The alkaline formulation (MLG-A50) showed this effect, distinguishing it from the standard MLG-50 formulation in this assay.
• Results were described as reflecting a 'pro-regenerative effect.'

Fulvic acid formulations exhibited anti-inflammatory activity by suppressing NF-κB activation in LPS-stimulated monocytes.

• Anti-inflammatory activity was assessed in LPS-stimulated monocytes.
• Suppression of NF-κB activation was demonstrated via two mechanisms: LPS neutralization and receptor-level inhibition.
• Reduced TNF and IL-6 secretion was observed.
• IL-10 production was not impaired, suggesting a selective anti-inflammatory profile rather than general immune suppression.

In vitro microbiome profiling revealed stimulation of beneficial bacterial taxa and reduced growth of pathogenic strains following exposure to fulvic acid formulations.

• Beneficial taxa stimulated included Lactobacillus and Clostridia spp.
• Reduced growth was observed in pathogenic bacterial strains.
• Both in vitro and in vivo microbial systems were used for assessment.
• Results were consistent across both MLG-50 and MLG-A50 formulations.

In vivo supplementation with MLG-50 and MLG-A50 increased microbial diversity and the abundance of health-associated bacterial taxa.

• In vivo supplementation was conducted with both MLG-50 and MLG-A50 formulations.
• Results demonstrated increased microbial diversity following supplementation.
• An increase in the abundance of health-associated taxa was observed.
• In vivo findings complemented the in vitro microbiome profiling data.