Alexandre Tavartkiladze*, Gaiane Simonia, Russel J Reiter, Ruite Lou, Nana Okrostsvaridze, Pati Revazishvili, Irine Andronikashvili, Pirdara Nozadze, Givi Tavartkiladze, Tamar Japaridze, Tatia Potskhoraia, Malvina Javakhadze
Background: Metastatic prostate cancer remains one of the leading causes of cancer-related morbidity and mortality in men worldwide. Despite advances in Androgen Deprivation Therapies (ADT), chemotherapy, targeted agents, and immunotherapies, many patients develop therapeutic resistance and experience significant toxicities. Dysregulated metabolic and inflammatory pathways, such as heightened glycolysis, increased proinflammatory cytokines, elevated Matrix Metalloproteinases (particularly MMP-9), and Androgen Receptor splice variants (e.g., AR-V7), can further drive disease progression. Emerging evidence suggests that optimizing host biology through circadian rhythm support, antioxidant defense, and modulation of immune function may confer therapeutic benefits. We conducted a double-blind, placebo-controlled study in 52 men to evaluate the effects of AminoTriComplex, a natural multi-component formulation that integrates advanced “molecular activation” and liposomalization technology to enhance bioavailability. AminoTriComplex contains key plant-derived bioactive molecules and melatonin in a specialized matrix hypothesized to modulate metabolic, inflammatory, and androgen-driven processes. Methods: Twenty-seven men with Metastatic Prostate Cancer (mPCa) composed the treatment group, while 25 age matched healthy men served as controls. The treatment group received AminoTriComplex plus standard-of-care therapies (as clinically indicated), whereas the control group received a placebo. Blood samples were collected at baseline, 6 weeks, and 12 weeks to measure Prostate-Specific Antigen (PSA), Matrix Metalloproteinase-9 (MMP-9), Proinflammatory Cytokines (IL-6, TNF-α, IL-8, and others), Androgen Receptor splice variant 7 (AR-V7) expression, bone turnover markers (e.g., alkaline phosphatase, P1NP, β-CTX), neuroendocrine markers (e.g., chromogranin A), and selected microRNAs (miRNA-17, miRNA-21, miRNA-141, miRNA-200, miRNA-375, etc.). We also measured melatonin levels at four distinct time points (06:00, 12:00, 21:00, and 02:00) to gauge circadian integrity. Patients were followed for 12 weeks to assess changes in biomarker profiles, tumor progression, and clinical status. Results: Ninety-five percent (95%) of men receiving AminoTriComplex demonstrated meaningful clinical improvement, defined as radiographically stable disease or regression, improved performance status (ECOG 0–1 in most), and reduced analgesic requirements. A sharp decrease in PSA (median -60.2%, p<0.001) was observed in the treatment group compared to placebo. MMP-9 levels fell by an average of 45% (compared to 3% in placebo, p<0.001). Inflammatory cytokine levels (IL-6, TNF-α, IL-8) dropped significantly, mirroring improvements in systemic inflammation scores. AR-V7 expression, detected in circulating tumor cells in 30% of patients at baseline, was reduced or became undetectable in over half of those AR-V7-positive patients. MicroRNAs associated with aggressive disease (e.g., miRNA-21, miRNA-141) were significantly reduced, while beneficial immune-related and tumor-suppressor miRNAs (e.g., miRNA-218-5p) were upregulated. Circadian assessment showed improved nocturnal melatonin peaks in 80% of treated individuals, correlated with better biomarker changes. Conclusion: AminoTriComplex, when combined with standard-of-care therapies, appears safe and highly effective in improving clinical outcomes for men with metastatic prostate cancer. It induced a sharp reduction in PSA, lowered MMP-9 and proinflammatory cytokines, modulated microRNAs, reduced AR-V7 expression, and improved circadian markers in 95% of patients. This study highlights the importance of combining natural multi-component strategies with conventional regimens to modulate key hallmarks of tumor progression. Further larger, multi-center trials are warranted to confirm these promising findings and elucidate the mechanistic basis of AminoTriComplex’s robust effects on prostate cancer biology. Keywords: Metastatic prostate cancer; Aminotricomplex; Melatonin, PSA reduction; Inflammatory cytokines; MicroRNA modulation; Circadian rhythm; Clinical improvement.
Published Date: 2025-03-24; Received Date: 2025-02-21