Anti-Inflammatory, Antioxidant, and Anti-Atherosclerotic Effects of Natural Supplements on Patients with FMF-Related AA Amyloidosis: A Non-Randomized 24-Week Open-Label Interventional Study
Micol Romano,
Facundo Garcia-Bournissen,
David Piskin,
Ulkumen Rodoplu,
Lizzy Piskin,
Abdelbaset A. Elzagallaai,
Tunc Tuncer,
Siren Sezer,
Didar Ucuncuoglu,
Tevfik Honca,
Dimitri Poddighe,
Izzet Yavuz,
Peter Stenvinkel,
Mahmut Ilker Yilmaz,
Erkan Demirkaya
Affiliations
Micol Romano
Department of Paediatrics, Division of Paediatric Rheumatology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5W9, Canada
Facundo Garcia-Bournissen
Department of Paediatrics, Division of Paediatric Clinical Pharmacology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5W9, Canada
David Piskin
Canadian Behcet and Autoinflammatory Disease Center (CAN BE AID), Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5W9, Canada
Ulkumen Rodoplu
Emergency Medicine Association of Turkey of All, 35220 Izmir, Turkey
Lizzy Piskin
Robarts Research Institute, University of Western Ontario, London, ON N6A 3K7, Canada
Abdelbaset A. Elzagallaai
Schulich School of Medicine & Dentistry, Physiology and Pharmacology, University of Western Ontario, London, ON N6A 3K7, Canada
Tunc Tuncer
Unit of Biochemistry, Epigenetic Health Solutions, 06810 Ankara, Turkey
Siren Sezer
Division of Nephrology, Faculty of Medicine, Atilim University, 06830 Ankara, Turkey
Didar Ucuncuoglu
Department of Food Engineering, Faculty of Engineering, Cankiri Karatekin University, 18100 Cankiri, Turkey
Tevfik Honca
Unit of Biochemistry, Gur Life Hospital, 26320 Eskisehir, Turkey
Dimitri Poddighe
Department of Medicine, Nazarbayev University School of Medicine, Nur-Sultan 010000, Kazakhstan
Izzet Yavuz
Department of Nephrology, Lokman Hekim University, 06510 Ankara, Turkey
Peter Stenvinkel
Department of Renal Medicine M99, Karolinska Institute, Karolinska University Hospital, 17164 Stockholm, Sweden
Mahmut Ilker Yilmaz
Unit of Nephrology, Center for Epigenetic Health Solutions, 06810 Ankara, Turkey
Erkan Demirkaya
Department of Paediatrics, Division of Paediatric Rheumatology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5W9, Canada
We aimed to evaluate the effect of a combination of natural products on parameters related to inflammation, endothelial dysfunction, and oxidative stress in a cohort of familial Mediterranean fever (FMF) patients with Serum Amyloid A amyloidosis, in a non-randomized, 24-week open-label interventional study. Morinda citrifolia (anti-atherosclerotic-AAL), omega-3 (anti-inflammatory-AIC), and extract with Alaskan blueberry (antioxidant-AOL) were given to patients with FMF-related biopsy-proven AA amyloidosis. Patients were >18 years and had proteinuria (>3500 mg/day) but a normal estimated glomerular filtration rate (eGFR). Arterial flow-mediated dilatation (FMD), carotid intima media thickness (CIMT), and serum biomarkers asymmetric dimethylarginine (ADMA), high sensitivity C-reactive protein (hs-CRP), pentraxin (PTX3), malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and glutathione peroxidase (GSH-Px) were studied at baseline and after 24 weeks of treatment. A total of 67 FMF-related amyloidosis patients (52 male (77.6%); median age 36 years (range 21–66)) were enrolled. At the end of a 24-week treatment period with AAL, AIC, and AOL combination therapy, ADMA, MDA, PTX3, hsCRP, cholesterol, and proteinuria were significantly decreased compared to baseline, while CuZn-SOD, GSH-Px, and FMD levels were significantly increased. Changes in inflammatory markers PTX3, and hsCRP were negatively correlated with FMD change, and positively correlated with decreases in proteinuria, ADMA, MDA, cholesterol, and CIMT. Treatment with AAL, AIC and AOL combination for 24 weeks were significantly associated with reduction in inflammatory markers, improved endothelial functions, and oxidative state. Efficient control of these three mechanisms can have long term cardiovascular and renal benefits for patients with AA amyloidosis.
