From the Research
There is no direct association between fulvic acid, humic acid, and Balkan nephropathy based on the most recent and highest quality evidence available. The etiology of Balkan endemic nephropathy (BEN) has been extensively studied, and while various environmental toxins have been proposed as potential causes, the most recent research points towards aristolochic acid as the primary causative agent 1. BEN is a chronic tubulointerstitial disease characterized by its endemic nature, primarily affecting rural areas along the Danube River in countries such as Romania, Bulgaria, Serbia, Bosnia and Herzegovina, and Croatia.
The mechanism by which BEN develops involves the consumption of food contaminated with aristolochic acid, a toxin produced by plants of the genus Aristolochia, which can contaminate wheat fields and subsequently be ingested through bread made from contaminated grain 1, 2. This exposure leads to the formation of aristolactam-DNA adducts in renal tissue, which are not only biomarkers of prior exposure to aristolochic acid but also trigger urothelial malignancy by inducing specific mutations in critical genes of carcinogenesis 1.
While fulvic and humic acids are naturally occurring substances found in the environment and have been studied for various health effects, the current evidence does not directly link these compounds to the causation of Balkan nephropathy. The focus of recent high-quality research has been on aristolochic acid due to its strong association with the disease, as evidenced by the detection of specific molecular signatures in affected individuals 1.
Key points regarding the association of environmental toxins with BEN include:
- Aristolochic acid is identified as the primary causative agent of BEN based on recent and high-quality evidence 1, 2.
- The disease is characterized by its endemic nature and slow progression to end-stage renal disease, often associated with upper urinary tract tumors 1, 3.
- The role of other potential environmental toxins, including fulvic and humic acids, in the etiology of BEN is not supported by the most recent and highest quality evidence available.
In clinical practice, understanding the etiology of BEN is crucial for developing effective prevention and intervention strategies. Given the strong evidence linking aristolochic acid to BEN, efforts should focus on reducing exposure to this toxin, particularly through dietary changes and agricultural practices that minimize contamination of grain fields with Aristolochia plants.