Evaluation of the efficacy and absorption of a nutraceutical product: pilot study
Keywords:
antioxidant, aging, oxidative stress, skin aging, coenzyme Q10Abstract
Background and aim: Oxidative stress is a process involved in aging and numerous human pathologies. The aim of this study was to evaluate the safety and efficacy of MITOFAST® in increasing the levels of markers linked to oxidative stress in plasma and red blood cells of healthy subjects
Methods: Prospective pilot study conducted on 22 healthy adult subjects. All participants received two sachets/day for 30 days of a commercial supplement containing a blend of antioxidant micronutrients (Coenzyme Q10, resveratrol, vitamin C, folic acid, and N-acetylcysteine). At enrolment (T0) and after 4 weeks (T1), blood samples were taken to evaluate homocysteine, gluthatione, coenzyme Q10, cysteinylglycine, cysteine, vitamin C, and vitamin E. Furthermore, any side effects reported by the subjects were evaluated. P-value <0.05 was considered statistically significant.
Results: Vitamin E, coenzyme Q10, and total plasma gluthatione levels significantly increased, whereas vitamin C remained constant after treatment. Homocysteine concentration decreased due to folic acid content (p= 0.003).
Conclusions: The overall increase in the levels of antioxidant molecules measured, together with the reduction of cysteinylglycine and homocysteine, indicate an antioxidant activity of MITOFAST®
References
Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552(Pt 2):335-44. doi: 10.1113/jphysiol.2003.049478
Li X, Fang P, Mai J, Choi ET, Wang H, Yang XF. Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers. J Hematol Oncol. 2013;6:19. doi: 10.1186/1756-8722-6-19
Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med. 2000;29(3-4):222-30. doi: 10.1016/s0891-5849(00)00317-8
Hrycay EG, Bandiera SM. Involvement of Cytochrome P450 in Reactive Oxygen Species Formation and Cancer. Adv Pharmacol. 2015;74:35-84. doi: 10.1016/bs.apha.2015.03.003
de Roos B, Duthie GG. Role of dietary pro-oxidants in the maintenance of health and resilience to oxidative stress. Mol Nutr Food Res. 2015 Jul;59(7):1229-48. doi: 10.1002/mnfr.201400568
Das SK, Vasudevan DM. Alcohol-induced oxidative stress. Life Sci. 2007;81(3):177-87. doi: 10.1016/j.lfs.2007.05.005
Bailey SM, Pietsch EC, Cunningham CC. Ethanol stimulates the production of reactive oxygen species at mitochondrial complexes I and III. Free Radic Biol Med. 1999;27(7-8):891-900. doi: 10.1016/s0891-5849(99)00138-0
van der Vaart H, Postma DS, Timens W, ten Hacken NH. Acute effects of cigarette smoke on inflammation and oxidative stress: a review. Thorax. 2004;59(8):713-21. doi: 10.1136/thx.2003.012468
Prasad A, Pospíšil P. Ultraweak photon emission induced by visible light and ultraviolet A radiation via photoactivated skin chromophores: in vivo charge coupled device imaging. J Biomed Opt. 2012;17(8):085004. doi: 10.1117/1.JBO.17.8.085004
Rinnerthaler M, Bischof J, Streubel MK, Trost A, Richter K. Oxidative stress in aging human skin. Biomolecules. 2015;5(2):545-89. doi: 10.3390/biom5020545
Berneburg M, Gattermann N, Stege H, et al. Chronically ultraviolet-exposed human skin shows a higher mutation frequency of mitochondrial DNA as compared to unexposed skin and the hematopoietic system. Photochem Photobiol. 1997;66(2):271-5. doi:10.1111/j.1751-1097.1997.tb08654.x
Bickers DR, Athar M. Oxidative stress in the pathogenesis of skin disease. J Invest Dermatol. 2006;126(12):2565-75. doi: 10.1038/sj.jid.5700340
Dröge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002;82(1):47-95. doi: 10.1152/physrev.00018.2001
Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. Int J Biomed Sci. 2008;4(2):89-96
Bhardwaj RL, Pandey S. Juice blends--a way of utilization of under-utilized fruits, vegetables, and spices: a review. Crit Rev Food Sci Nutr. 2011;51(6):563-70. doi: 10.1080/10408391003710654
Milisav I, Ribarič S, Poljsak B. Antioxidant Vitamins and Ageing. Subcell Biochem. 2018; 90: 1-23. doi: 10.1007/978-981-13-2835-0_1
Koushki M, Lakzaei M, Khodabandehloo H, Hosseini H, Meshkani R, Panahi G. Therapeutic effect of resveratrol supplementation on oxidative stress: a systematic review and meta-analysis of randomised controlled trials. Postgrad Med J. 2020; 96(1134): 197-205. doi: 10.1136/postgradmedj-2019-136415
Asbaghi O, Ghanavati M, Ashtary-Larky D, et al. Effects of Folic Acid Supplementation on Oxidative Stress Markers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Antioxidants (Basel). 2021; 10(6): 871. doi: 10.3390/antiox10060871
Aaseth J, Alexander J, Alehagen U. Coenzyme Q10 supplementation - In ageing and disease. Mech Ageing Dev. 2021 Jul;197:111521. doi: 10.1016/j.mad.2021.111521
Raghu G, Berk M, Campochiaro PA, et al. The Multifaceted Therapeutic Role of N-Acetylcysteine (NAC) in Disorders Characterized by Oxidative Stress. Curr Neuropharmacol. 2021; 19(8): 1202-1224. doi: 10.2174/1570159X19666201230144109
Prior RL, Cao G. Antioxidant phytochemicals in fruits and vegetables: dietary and health implications. Hortic Sci. 2000;35:588-592
Paganaga G, Miller N, Rice-Evans CA. The polypohenolic content of fruit and vegetables and their antioxidant activities: what does a serving constitute? Free Radic Res. 1999;30:153-162
Halvorsen BL, Holte K, Myhrstad MC, et al. A systematic screening of total antioxidants in dietary plants. J Nutr. 2002;132:461-471
Wild AC, Mulcahy RT. Regulation of gamma-glutamylcysteine synthetase subunit gene expression: insights into transcriptional control of antioxidant defenses. Free Radic Res. 2000;32:281-301.
Hayes JD, McLellan LI. Glutathione and glutathione dependent enzymes represent a coordinately regulated defense against oxidative stress. Free Radic Res. 1999;31:273-300.
Sen CK, Packer L. Antioxidant and redox regulation of gene transcription. FASEB J. 1996;10:709-720.
Talalay P. Chemoprotection against cancer by induction of phase 2 enzymes. Biofactors. 2000;12:5-11.
Festi D, Colecchia A, Pini S, et al. Development and application of a simple and powerful tool for nutrition and lifestyle education for the Italian general population by general practitioners and family paediatricians. MJNM. 2009;2:139-144
Vigna L, Cassinelli L, Tirelli AS, et al. 25(OH)D Levels in Relation to Gender, Overweight, Insulin Resistance, and Inflammation in a Cross-Sectional Cohort of Northern Italian Workers: Evidence in Support of Preventive Health Care Programs. J Am Coll Nutr. 2017; 36(4): 253-260. doi: 10.1080/07315724.2016.1264280
Dellanoce C, Cozzi L, Zuddas S, Pratali L, Accinni R. Determination of different forms of aminothiols in red blood cells without washing erythrocytes. Biomed Chromatogr. 2014; 28(3): 327-31. doi: 10.1002/bmc.3056
Svardal AM, Mansoor MA, Ueland PM. Determination of reduced, oxidized, and protein-bound glutathione in human plasma with precolumn derivatization with monobromobimane and liquid chromatography. Anal Biochem. 1990; 184(2): 338-46. doi: 10.1016/0003-2697(90)90691-2
Serra-Majem L, Tomaino L, Dernini S, et al. Updating the Mediterranean Diet Pyramid towards Sustainability: Focus on Environmental Concerns. Int J Environ Res Public Health. 2020;17(23):8758. doi: 10.3390/ijerph17238758
Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015;14:6. doi: 10.1186/1475-2891-14-6
Wu X, Zhang L, Miao Y, et al. Homocysteine causes vascular endothelial dysfunction by disrupting endoplasmic reticulum redox homeostasis. Redox Biol. 2019;20:46-59. doi: 10.1016/j.redox.2018.09.021
Balint B, Jepchumba VK, Guéant JL, Guéant-Rodriguez RM. Mechanisms of homocysteine-induced damage to the endothelial, medial and adventitial layers of the arterial wall. Biochimie. 2020;173:100-106. doi: 10.1016/j.biochi.2020.02.012
Yang Q, He GW. Imbalance of Homocysteine and H2S: Significance, Mechanisms, and Therapeutic Promise in Vascular Injury. Oxid Med Cell Longev. 2019;2019:7629673. doi: 10.1155/2019/7629673
Lim U, Cassano PA. Homocysteine and blood pressure in the Third National Health and Nutrition Examination Survey, 1988-1994. Am J Epidemiol. 2002;156(12):1105-13. doi: 10.1093/aje/kwf157
Gori F, Tirelli AS, Piontini A, et al. Metabolic Syndrome, Homocysteine and Uric Acid in Patients with Obesity; Experience from Obesity and Work Centre. Mediterranean Journal of Nutrition and Metabolism. 2021: 277-288
Zaric BL, Obradovic M, Bajic V, Haidara MA, Jovanovic M, Isenovic ER. Homocysteine and Hyperhomocysteinaemia. Curr Med Chem. 2019;26(16):2948- 2961. doi: 10.2174/0929867325666180313105949
Bhagavan HN, Chopra RK. Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006;40(5):445-53. doi: 10.1080/10715760600617843
Bhagavan HN, Chopra RK. Plasma coenzyme Q10 response to oral ingestion of coenzyme Q10 formulations. Mitochondrion. 2007;7 Suppl:S78-88. doi: 10.1016/j.mito.2007.03.003
Judy WV. The Single-dose Absorption and Steady-state Bioavailability of Different Coenzyme Q10 Formulations. Integr Med (Encinitas). 2022;21(1):28-34
Saini R. Coenzyme Q10: The essential nutrient. J Pharm Bioallied Sci. 2011;3(3):466-7. doi: 10.4103/0975-7406.84471
Aberg F, Appelkvist EL, Dallner G, Ernster L. Distribution and redox state of ubiquinones in rat and human tissues. Arch Biochem Biophys 1992;295:230–234
Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr. 2001;20(6):591-8. doi: 10.1080/07315724.2001.10719063
Gutierrez-Mariscal FM, Arenas-de Larriva AP, Limia-Perez L, Romero-Cabrera JL, Yubero-Serrano EM, López-Miranda J. Coenzyme Q10 Supplementation for the Reduction of Oxidative Stress: Clinical Implications in the Treatment of Chronic Diseases. Int J Mol Sci. 2020;21(21):7870. doi: 10.3390/ijms21217870
Arenas-Jal M, Suñé-Negre JM, García-Montoya E. Coenzyme Q10 supplementation: Efficacy, safety, and formulation challenges. Compr Rev Food Sci Food Saf. 2020;19(2):574-594. doi: 10.1111/1541-4337.12539
Langsjoen PH, Langsjoen AM. Overview of the use of CoQ10 in cardiovascular disease. Biofactors. 1999;9(2-4):273-84. doi: 10.1002/biof.5520090224
Akbari A, Mobini GR, Agah S, et al. Coenzyme Q10 supplementation and oxidative stress parameters: a systematic review and meta-analysis of clinical trials. Eur J Clin Pharmacol. 2020; 76(11): 1483-1499. doi: 10.1007/s00228-020-02919-8
Sangsefidi ZS, Yaghoubi F, Hajiahmadi S, Hosseinzadeh M. The effect of coenzyme Q10 supplementation on oxidative stress: A systematic review and meta-analysis of randomized controlled clinical trials. Food Sci Nutr. 2020; 8(4): 1766-1776. doi: 10.1002/fsn3.1492
Ouchi A, Nagaoka S, Mukai K. Tunneling effect in regeneration reaction of vitamin E by ubiquinol. J Phys Chem B. 2010;114(19):6601-7. doi: 10.1021/jp910856m
Huang A, Vita JA, Venema RC, Keaney JF Jr. Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. J Biol Chem. 2000 Jun 9;275(23):17399-406. doi: 10.1074/jbc.M002248200
Askari M, Faryabi R, Mozaffari H, Darooghegi Mofrad M. The effects of N-Acetylcysteine on serum level of inflammatory biomarkers in adults. Findings from a systematic review and meta-analysis of randomized clinical trials. Cytokine. 2020; 135: 155239. doi: 10.1016/j.cyto.2020.155239
Rushworth GF, Megson IL. Existing and potential therapeutic uses for N- acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther. 2014;141(2):150-9. doi: 10.1016/j.pharmthera.2013.09.006
Raftos JE, Whillier S, Kuchel PW. Glutathione synthesis and turnover in the human erythrocyte: alignment of a model based on detailed enzyme kinetics with experimental data. J Biol Chem. 2010;285(31):23557-67. doi: 10.1074/jbc.M109.067017
Rifkind JM, Mohanty JG, Nagababu E. The pathophysiology of extracellular hemoglobin associated with enhanced oxidative reactions. Front Physiol. 2015;5:500. doi: 10.3389/fphys.2014.00500
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Laura Tomaino, Francesca Gori, Cinzia Dellanoce, Alessandra Piontini, Maria Rosaria Ingenito, Vittoria Di Donna, Filomena Napolitano, Vincenzo Soresi, Luisella Vigna, Andrea Fratter

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.