Health Risks of Cyanotoxin Contamination in Dietary Supplements: Mechanistic Insights into Organ-Specific Toxicity.

Abstract

Cyanotoxin contamination of cyanobacteria- and microalgae-derived dietary supplements poses an emerging public health concern despite their widespread use for nutritional and therapeutic purposes. This review critically examines the occurrence of cyanotoxins in commercially available Arthrospira (formerly Spirulina), Aphanizomenon flos-aquae, and Chlorella supplements and comprehensively summarizes the molecular mechanisms underlying organ-specific toxicity induced by major cyanotoxins, including microcystins, nodularin, cylindrospermopsin, anatoxins, saxitoxins, and β-N-methylamino-L-alanine (BMAA). Tissue-specific accumulation and differential cellular susceptibility drive distinct toxicological outcomes. In the liver, cyanotoxins disrupt serine/threonine protein phosphatase signaling, mitochondrial function, and redox homeostasis, resulting in oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, and carcinogenesis. Neurotoxicity is characterized by excitotoxicity, impaired neurotransmission, calcium dysregulation, neuroinflammation, and neuronal death, whereas renal, gastrointestinal, cardiovascular, pulmonary, and reproductive toxicities involve interconnected mechanisms including oxidative damage, mitochondrial dysfunction, inflammatory signaling, and metabolic disruption. Despite substantial progress, important knowledge gaps remain regarding chronic low-dose exposure, bioavailability from dietary supplements, and long-term human health effects. Future studies integrating toxicokinetics, multi-omics approaches, and validated biomarkers are essential to strengthen risk assessment, improve regulatory oversight, and ensure the safety of cyanobacteria- and microalgae-derived dietary supplements.