Evaluation of the efficacy and absorption of a nutraceutical product: pilot study
Main Article Content
Keywords
antioxidant, aging, oxidative stress, skin aging, coenzyme Q10
Abstract
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
2. 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
3. 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
4. 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
5. 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
6. Das SK, Vasudevan DM. Alcohol-induced oxidative stress. Life Sci. 2007;81(3):177-87. doi: 10.1016/j.lfs.2007.05.005
7. 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
8. 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
9. 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
10. 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
11. 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
12. 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
13. Dröge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002;82(1):47-95. doi: 10.1152/physrev.00018.2001
14. Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. Int J Biomed Sci. 2008;4(2):89-96
15. 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
16. 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
17. 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
18. 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
19. 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
20. 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
21. Prior RL, Cao G. Antioxidant phytochemicals in fruits and vegetables: dietary and health implications. Hortic Sci. 2000;35:588-592
22. 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
23. Halvorsen BL, Holte K, Myhrstad MC, et al. A systematic screening of total antioxidants in dietary plants. J Nutr. 2002;132:461-471
24. 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.
25. Hayes JD, McLellan LI. Glutathione and glutathione dependent enzymes represent a coordinately regulated defense against oxidative stress. Free Radic Res. 1999;31:273-300.
26. Sen CK, Packer L. Antioxidant and redox regulation of gene transcription. FASEB J. 1996;10:709-720.
27. Talalay P. Chemoprotection against cancer by induction of phase 2 enzymes. Biofactors. 2000;12:5-11.
28. 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
29. 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
30. 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
31. 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
32. 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
33. 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
34. 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
35. 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
36. 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
37. 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
38. 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
39. 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
40. Bhagavan HN, Chopra RK. Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006;40(5):445-53. doi: 10.1080/10715760600617843
41. 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
42. Judy WV. The Single-dose Absorption and Steady-state Bioavailability of Different Coenzyme Q10 Formulations. Integr Med (Encinitas). 2022;21(1):28-34
43. Saini R. Coenzyme Q10: The essential nutrient. J Pharm Bioallied Sci. 2011;3(3):466-7. doi: 10.4103/0975-7406.84471
44. 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
45. Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr. 2001;20(6):591-8. doi: 10.1080/07315724.2001.10719063
46. 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
47. 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
48. 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
49. 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
50. 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
51. 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
52. 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
53. 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
54. 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
55. 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
56. 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