{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:45:23Z","timestamp":1788187523461,"version":"build-2803163510"},"reference-count":110,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T00:00:00Z","timestamp":1756512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hamilton Health Sciences Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Ovarian aging is characterized by mitochondrial dysfunction, oxidative stress, and inflammation. The development of adjunctive treatments that mitigate age-related subfertility is warranted. We examined the benefits of nutraceutical supplementation (FE; Fertility Enhancer) with mitochondrial antioxidants, anti-inflammatory agents, metabolic activators, vitamins and minerals, and amino acids on ovarian aging, metabolic activity, and reproductive success in young (Y; 6-month-old) and middle-aged (O; 11-month-old) female C57BL\/6J mice. The mice were fed calorie- and macronutrient-matched diets w\/wo the FE supplement for three months and harem mated twice. Daily FE supplementation promoted significant body re-composition, including loss of white adipose tissue (gWAT: \u221236% vs. CON, p &lt; 0.001), gain of skeletal muscle (SkM: +67% vs. CON, p &lt; 0.001), and improved SkM\/gWAT ratio (+185% vs. CON, p &lt; 0.001). Metabolic testing showed enhanced fat oxidation (+38%, p &lt; 0.01) and energy expenditure (+7%, p = 0.051) in FE mice. Breeding and immunoblotting data demonstrated improved reproductive success (Y-CON: 44%, Y-FE: 89%, O-CON: 0%, O-FE: 18%) and a modest attenuation of ovarian aging markers in both FE groups. We surmise that a multi-ingredient supplement, such as the Fertility Enhancer, may improve body re-composition, metabolic activity, and markers of ovarian aging, thus enhancing reproductive health and fertility in females.<\/jats:p>","DOI":"10.3390\/biom15091258","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T08:28:15Z","timestamp":1756715295000},"page":"1258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Multi-Ingredient Supplement Improves Body Re-Composition, Ovarian Aging Markers, and Reproductive Success in Young and Middle-Aged Female Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Alessandra","family":"Chiarot","sequence":"first","affiliation":[{"name":"Department of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L86 4L8, Canada"},{"name":"Department of Kinesiology, McMaster University, Hamilton, ON L86 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahek","family":"Minhas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L86 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta M.","family":"de Maat","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L86 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Doan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L86 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5656-5578","authenticated-orcid":false,"given":"Mats I.","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Exerkine Corporation, McMaster University Medical Center (MUMC), Hamilton, ON L86 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart P.","family":"Hettinga","sequence":"additional","affiliation":[{"name":"Exerkine Corporation, McMaster University Medical Center (MUMC), Hamilton, ON L86 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrnoosh","family":"Faghih","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, McMaster University Medical Center (MUMC), Hamilton, ON L86 4L8, Canada"},{"name":"One Fertility, Burlington, ON L7N 3T1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4670-018X","authenticated-orcid":false,"given":"Michael S.","family":"Neal","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, McMaster University Medical Center (MUMC), Hamilton, ON L86 4L8, Canada"},{"name":"One Fertility, Burlington, ON L7N 3T1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua P.","family":"Nederveen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L86 4L8, Canada"},{"name":"Department of Kinesiology, McMaster University, Hamilton, ON L86 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0312-3746","authenticated-orcid":false,"given":"Mark A.","family":"Tarnopolsky","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L86 4L8, Canada"},{"name":"Exerkine Corporation, McMaster University Medical Center (MUMC), Hamilton, ON L86 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/humupd\/dms043","article-title":"The ageing ovary and uterus: New biological insights","volume":"19","author":"Nelson","year":"2013","journal-title":"Hum. Reprod. Update"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wu, J., Liu, Y., Song, Y., Wang, L., Ai, J., and Li, K. (2022). Aging conundrum: A perspective for ovarian aging. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.952471"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.cell.2020.01.009","article-title":"Single-Cell Transcriptomic Atlas of Primate Ovarian Aging","volume":"180","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/s43587-024-00762-5","article-title":"Molecular and genetic insights into human ovarian aging from single-nuclei multi-omics analyses","volume":"5","author":"Jin","year":"2025","journal-title":"Nat. Aging"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1126\/science.3755843","article-title":"Age and infertility","volume":"233","author":"Menken","year":"1986","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/humupd\/dml056","article-title":"The impact of lifestyle factors on reproductive performance in the general population and those undergoing infertility treatment: A review","volume":"13","author":"Homan","year":"2007","journal-title":"Hum. Reprod. Update"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sharma, R., Biedenharn, K.R., Fedor, J.M., and Agarwal, A. (2013). Lifestyle factors and reproductive health: Taking control of your fertility. Reprod. Biol. Endocrinol., 11.","DOI":"10.1186\/1477-7827-11-66"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s11357-016-9884-3","article-title":"Obesity and related consequences to ageing","volume":"38","author":"Jura","year":"2016","journal-title":"Age"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1210\/endrev\/bnad027","article-title":"Obesity-Related Hypogonadism in Women","volume":"45","author":"Eng","year":"2024","journal-title":"Endocr. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1126\/science.adi4736","article-title":"Muscle-derived myostatin is a major endocrine driver of follicle-stimulating hormone synthesis","volume":"387","author":"Ongaro","year":"2025","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1126\/science.adu7735","article-title":"Myostatin\u2019s flex on the reproductive hormone axis","volume":"387","author":"Steenwinkel","year":"2025","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Nederveen, J.P., Mastrolonardo, A.J., Xhuti, D., Di Carlo, A., Manta, K., Fuda, M.R., and Tarnopolsky, M.A. (2023). Novel Multi-Ingredient Supplement Facilitates Weight Loss and Improves Body Composition in Overweight and Obese Individuals: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients, 15.","DOI":"10.3390\/nu15173693"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Nilsson, M.I., Xhuti, D., de Maat, N.M., Hettinga, B.P., and Tarnopolsky, M.A. (2024). Obesity and Metabolic Disease Impair the Anabolic Response to Protein Supplementation and Resistance Exercise: A Retrospective Analysis of a Randomized Clinical Trial with Implications for Aging, Sarcopenic Obesity, and Weight Management. Nutrients, 16.","DOI":"10.3390\/nu16244407"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1016\/j.fertnstert.2009.04.029","article-title":"The economic impact of assisted reproductive technology: A review of selected developed countries","volume":"91","author":"Chambers","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.fertnstert.2005.08.066","article-title":"International disparities in access to infertility services","volume":"85","author":"Nachtigall","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"hoad007","DOI":"10.1093\/hropen\/hoad007","article-title":"Financial costs of assisted reproductive technology for patients in low- and middle-income countries: A systematic review","volume":"2023","author":"Njagi","year":"2023","journal-title":"Hum. Reprod. Open"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Dwyer, J.T., Coates, P.M., and Smith, M.J. (2018). Dietary Supplements: Regulatory Challenges and Research Resources. Nutrients, 10.","DOI":"10.3390\/nu10010041"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Vitagliano, A., Petre, G.C., Francini-Pesenti, F., De Toni, L., Di Nisio, A., Grande, G., Foresta, C., and Garolla, A. (2021). Dietary Supplements for Female Infertility: A Critical Review of Their Composition. Nutrients, 13.","DOI":"10.3390\/nu13103552"},{"key":"ref_19","unstructured":"WHO Antenatal Care Recommendations for a Positive Pregnancy Experience (2020). Nutritional Interventions Update: Multiple Micronutrient Supplements During Pregnancy, WHO."},{"key":"ref_20","first-page":"CD007950","article-title":"Effects and safety of periconceptional oral folate supplementation for preventing birth defects","volume":"2015","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"f3443","DOI":"10.1136\/bmj.f3443","article-title":"Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: Systematic review and meta-analysis","volume":"346","author":"Haider","year":"2013","journal-title":"BMJ Br. Med. J."},{"key":"ref_22","first-page":"CD004736","article-title":"Daily oral iron supplementation during pregnancy","volume":"12","author":"Dowswell","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_23","first-page":"CD004905","article-title":"Multiple-micronutrient supplementation for women during pregnancy","volume":"3","author":"Keats","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1017\/S0007114510000747","article-title":"Effect of multiple-micronutrient supplementation on maternal nutrient status, infant birth weight and gestational age at birth in a low-income, multi-ethnic population","volume":"104","author":"Brough","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/sj.ejcn.1601745","article-title":"Effects of a combined micronutrient supplementation on maternal biological status and newborn anthropometrics measurements: A randomized double-blind, placebo-controlled trial in apparently healthy pregnant women","volume":"58","author":"Hininger","year":"2004","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1093\/oxfordjournals.aje.a009244","article-title":"Use of Multivitamin\/Mineral Prenatal Supplements: Influence on the Outcome of Pregnancy","volume":"146","author":"Scholl","year":"1997","journal-title":"Am. J. Epidemiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kapper, C., Stelzl, P., Oppelt, P., Ganh\u00f6r, C., Gyunesh, A.A., Arbeithuber, B., and Rezk-F\u00fcreder, M. (2024). The Impact of Minerals on Female Fertility: A Systematic Review. Nutrients, 16.","DOI":"10.37766\/inplasy2024.2.0097"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"104462","DOI":"10.1016\/j.phrs.2019.104462","article-title":"Omega-3 fatty acids supplementation and oxidative stress parameters: A systematic review and meta-analysis of clinical trials","volume":"149","author":"Heshmati","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sley, E.G., Rosen, E.M., van \u2018t Erve, T.J., Sathyanarayana, S., Barrett, E.S., Nguyen, R.H.N., Bush, N.R., Milne, G.L., Swan, S.H., and Ferguson, K.K. (2020). Omega-3 fatty acid supplement use and oxidative stress levels in pregnancy. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0240244"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Haghiac, M., Yang, X.H., Presley, L., Smith, S., Dettelback, S., Minium, J., Belury, M.A., Catalano, P.M., and Hauguel-de Mouzon, S. (2015). Dietary Omega-3 Fatty Acid Supplementation Reduces Inflammation in Obese Pregnant Women: A Randomized Double-Blind Controlled Clinical Trial. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137309"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109104","DOI":"10.1016\/j.intimp.2022.109104","article-title":"Efficacy of the omega-3 fatty acids supplementation on inflammatory biomarkers: An umbrella meta-analysis","volume":"111","author":"Kavyani","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Li, K., Huang, T., Zheng, J., Wu, K., and Li, D. (2014). Effect of marine-derived n-3 polyunsaturated fatty acids on C-reactive protein, interleukin 6 and tumor necrosis factor \u03b1: A meta-analysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088103"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.mayocp.2020.08.034","article-title":"Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials","volume":"96","author":"Bernasconi","year":"2021","journal-title":"Mayo Clin. Proc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100997","DOI":"10.1016\/j.eclinm.2021.100997","article-title":"Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis","volume":"38","author":"Khan","year":"2021","journal-title":"eClinicalMedicine"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Liu, Y.X., Yu, J.H., Sun, J.H., Ma, W.Q., Wang, J.J., and Sun, G.J. (2023). Effects of Omega-3 Fatty Acids Supplementation on Serum Lipid Profile and Blood Pressure in Patients with Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Foods, 12.","DOI":"10.3390\/foods12040725"},{"key":"ref_36","first-page":"9455","article-title":"Does omega-3 PUFAs supplementation improve metabolic syndrome and related cardiovascular diseases? A systematic review and meta-analysis of randomized controlled trials","volume":"64","author":"Wang","year":"2024","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4435","DOI":"10.1080\/10408398.2021.1875977","article-title":"Omega-3 supplementation and diabetes: A systematic review and meta-analysis","volume":"62","author":"Delpino","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s12933-018-0740-x","article-title":"Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: A meta-analysis and meta-regression of randomized controlled trials","volume":"17","author":"Matu","year":"2018","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e35403","DOI":"10.1097\/MD.0000000000035403","article-title":"Meta-analysis of the efficacy of \u03c9-3 polyunsaturated fatty acids when treating patients with polycystic ovary syndrome","volume":"102","author":"Huang","year":"2023","journal-title":"Medicine"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Yang, K., Zeng, L., Bao, T., and Ge, J. (2018). Effectiveness of Omega-3 fatty acid for polycystic ovary syndrome: A systematic review and meta-analysis. Reprod. Biol. Endocrinol., 16.","DOI":"10.1186\/s12958-018-0346-x"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13048-023-01130-4","article-title":"Effects of n-3 polyunsaturated fatty acid on metabolic status in women with polycystic ovary syndrome: A meta-analysis of randomized controlled trials","volume":"16","author":"Zhou","year":"2023","journal-title":"J. Ovarian Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"101251","DOI":"10.1016\/j.ajogmf.2023.101251","article-title":"Omega-3 fatty acid supply in pregnancy for risk reduction of preterm and early preterm birth","volume":"6","author":"Cetin","year":"2024","journal-title":"Am. J. Obstet. Gynecol. MFM"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ejogrb.2015.11.033","article-title":"Effects of omega-3 fatty acids in prevention of early preterm delivery: A systematic review and meta-analysis of randomized studies","volume":"198","author":"Kar","year":"2016","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_44","first-page":"CD003402","article-title":"Omega 3 fatty acid addition during pregnancy","volume":"11","author":"Middleton","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"263ed21","DOI":"10.1126\/scitranslmed.aaa2563","article-title":"Preterm birth: Now the leading cause of child death worldwide","volume":"6","author":"Lawn","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1007\/s10815-020-01906-3","article-title":"Does coenzyme Q(10) supplementation improve fertility outcomes in women undergoing assisted reproductive technology procedures? A systematic review and meta-analysis of randomized-controlled trials","volume":"37","author":"Florou","year":"2020","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1080\/10408398.2018.1442316","article-title":"Coenzyme Q(10): From bench to clinic in aging diseases, a translational review","volume":"59","author":"Villalba","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100273","DOI":"10.1016\/j.advnut.2024.100273","article-title":"Antioxidants and Fertility in Women with Ovarian Aging: A Systematic Review and Meta-Analysis","volume":"15","author":"Shang","year":"2024","journal-title":"Adv. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1007\/s43032-022-01038-2","article-title":"Efficacy and Safety of Coenzyme Q10 Supplementation in the Treatment of Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis","volume":"30","author":"Zhang","year":"2023","journal-title":"Reprod. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"101602","DOI":"10.1016\/j.eclinm.2022.101602","article-title":"Effects of coenzyme Q10 supplementation on glycemic control: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials","volume":"52","author":"Liang","year":"2022","journal-title":"EClinicalMedicine"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nutres.2016.12.001","article-title":"A meta-analysis of randomized and placebo-controlled clinical trials suggests that coenzyme Q10 at low dose improves glucose and HbA1c levels","volume":"38","year":"2017","journal-title":"Nutr. Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Dludla, P.V., Orlando, P., Silvestri, S., Marcheggiani, F., Cirilli, I., Nyambuya, T.M., Mxinwa, V., Mokgalaboni, K., Nkambule, B.B., and Johnson, R. (2020). Coenzyme Q(10) Supplementation Improves Adipokine Levels and Alleviates Inflammation and Lipid Peroxidation in Conditions of Metabolic Syndrome: A Meta-Analysis of Randomized Controlled Trials. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093247"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.phrs.2017.01.032","article-title":"Effects of coenzyme Q10 supplementation on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials","volume":"119","author":"Fan","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e2200800","DOI":"10.1002\/mnfr.202200800","article-title":"Efficacy and Optimal Dose of Coenzyme Q10 Supplementation on Inflammation-Related Biomarkers: A GRADE-Assessed Systematic Review and Updated Meta-Analysis of Randomized Controlled Trials","volume":"67","author":"Hou","year":"2023","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Dai, S., Tian, Z., Zhao, D., Liang, Y., Liu, M., Liu, Z., Hou, S., and Yang, Y. (2022). Effects of Coenzyme Q10 Supplementation on Biomarkers of Oxidative Stress in Adults: A GRADE-Assessed Systematic Review and Updated Meta-Analysis of Randomized Controlled Trials. Antioxidants, 11.","DOI":"10.3390\/antiox11071360"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e00118","DOI":"10.1002\/edm2.118","article-title":"The impact of coenzyme Q(10) on metabolic and cardiovascular disease profiles in diabetic patients: A systematic review and meta-analysis of randomized controlled trials","volume":"3","author":"Dludla","year":"2020","journal-title":"Endocrinol. Diabetes Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1210\/clinem\/dgac585","article-title":"Effects of Coenzyme Q10 Supplementation on Lipid Profiles in Adults: A Meta-analysis of Randomized Controlled Trials","volume":"108","author":"Liu","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.freeradbiomed.2014.03.035","article-title":"Natural forms of vitamin E: Metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy","volume":"72","author":"Jiang","year":"2014","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/BF02524257","article-title":"Coenzyme Q and vitamin E need each other as antioxidants","volume":"214","author":"Kagan","year":"2000","journal-title":"Protoplasma"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0022-2275(20)41529-9","article-title":"Recycling of vitamin E in human low density lipoproteins","volume":"33","author":"Kagan","year":"1992","journal-title":"J. Lipid Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s12263-012-0286-6","article-title":"\u03b1-Tocopherol incorporation in mitochondria and microsomes upon supranutritional vitamin E supplementation","volume":"7","author":"Lauridsen","year":"2012","journal-title":"Genes Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/S0076-6879(04)78010-6","article-title":"Coenzyme Q and vitamin E interactions","volume":"378","author":"Sohal","year":"2004","journal-title":"Methods Enzymol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Asbaghi, O., Sadeghian, M., Nazarian, B., Sarreshtedari, M., Mozaffari-Khosravi, H., Maleki, V., Alizadeh, M., Shokri, A., and Sadeghi, O. (2020). The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: A systematic review and meta-analysis of randomized clinical trials. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-73741-6"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Tefagh, G., Payab, M., Qorbani, M., Sharifi, F., Sharifi, Y., Ebrahimnegad Shirvani, M.S., Pourghazi, F., Atlasi, R., Shadman, Z., and Rezaei, N. (2022). Effect of vitamin E supplementation on cardiometabolic risk factors, inflammatory and oxidative markers and hormonal functions in PCOS (polycystic ovary syndrome): A systematic review and meta-analysis. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-09082-3"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7522","DOI":"10.1074\/jbc.TM117.000259","article-title":"Lipoic acid metabolism and mitochondrial redox regulation","volume":"293","author":"Solmonson","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1111\/obr.12528","article-title":"Alpha-lipoic acid (ALA) as a supplementation for weight loss: Results from a meta-analysis of randomized controlled trials","volume":"18","author":"Kucukgoncu","year":"2017","journal-title":"Obes. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.clnu.2017.06.002","article-title":"Alpha-lipoic acid supplement in obesity treatment: A systematic review and meta-analysis of clinical trials","volume":"37","author":"Namazi","year":"2017","journal-title":"Clin. Nutr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e13493","DOI":"10.1111\/ijcp.13493","article-title":"Alpha-lipoic acid supplementation significantly reduces the risk of obesity in an updated systematic review and dose response meta-analysis of randomised placebo-controlled clinical trials","volume":"74","author":"Vajdi","year":"2020","journal-title":"Int. J. Clin. Pract."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12986-018-0274-y","article-title":"The effects of alpha-lipoic acid supplementation on inflammatory markers among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials","volume":"15","author":"Akbari","year":"2018","journal-title":"Nutr. Metab."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.metabol.2018.07.002","article-title":"The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials","volume":"87","author":"Akbari","year":"2018","journal-title":"Metab. Clin. Exp."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Guarano, A., Capozzi, A., Cristodoro, M., Di Simone, N., and Lello, S. (2023). Alpha Lipoic Acid Efficacy in PCOS Treatment: What Is the Truth?. Nutrients, 15.","DOI":"10.3390\/nu15143209"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"102599","DOI":"10.1016\/j.midw.2019.102599","article-title":"Acceptability of dietary or nutritional supplementation in pregnancy (ADONS)\u2014Exploring the consumer\u2019s perspective on introducing creatine monohydrate as a pregnancy supplement","volume":"82","author":"Palmer","year":"2020","journal-title":"Midwifery"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1111\/1471-0528.14237","article-title":"Maternal creatine in pregnancy: A retrospective cohort study","volume":"123","author":"Dickinson","year":"2016","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Dickinson, H., Ellery, S., Ireland, Z., LaRosa, D., Snow, R., and Walker, D.W. (2014). Creatine supplementation during pregnancy: Summary of experimental studies suggesting a treatment to improve fetal and neonatal morbidity and reduce mortality in high-risk human pregnancy. BMC Pregnancy Childbirth, 14.","DOI":"10.1186\/1471-2393-14-150"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12970-017-0173-z","article-title":"International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine","volume":"14","author":"Kreider","year":"2017","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Muccini, A.M., Tran, N.T., de Guingand, D.L., Philip, M., Della Gatta, P.A., Galinsky, R., Sherman, L.S., Kelleher, M.A., Palmer, K.R., and Berry, M.J. (2021). Creatine Metabolism in Female Reproduction, Pregnancy and Newborn Health. Nutrients, 13.","DOI":"10.3390\/nu13020490"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1017\/S000711452300260X","article-title":"The effects of green tea extract supplementation on body composition, obesity-related hormones and oxidative stress markers: A grade-assessed systematic review and dose-response meta-analysis of randomised controlled trials","volume":"131","author":"Asbaghi","year":"2024","journal-title":"Br. J. Nutr."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1038\/ijo.2009.135","article-title":"The effects of green tea on weight loss and weight maintenance: A meta-analysis","volume":"33","author":"Hursel","year":"2009","journal-title":"Int. J. Obes."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"6713194","DOI":"10.1155\/2019\/6713194","article-title":"The Bioprotective Effects of Polyphenols on Metabolic Syndrome against Oxidative Stress: Evidences and Perspectives","volume":"2019","author":"Liu","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1093\/ajcn\/79.5.727","article-title":"Polyphenols: Food sources and bioavailability","volume":"79","author":"Manach","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Rasaei, N., Asbaghi, O., Samadi, M., Setayesh, L., Bagheri, R., Gholami, F., Soveid, N., Casazza, K., Wong, A., and Suzuki, K. (2021). Effect of Green Tea Supplementation on Antioxidant Status in Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Antioxidants, 10.","DOI":"10.3390\/antiox10111731"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.rbmo.2017.02.006","article-title":"Potential role of green tea catechins in the management of oxidative stress-associated infertility","volume":"34","author":"Roychoudhury","year":"2017","journal-title":"Reprod. Biomed. Online"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Nilsson, M.I., May, L., Roik, L.J., Fuda, M.R., Luo, A., Hettinga, B.P., Bujak, A.L., and Tarnopolsky, M.A. (2023). A Multi-Ingredient Supplement Protects against Obesity and Infertility in Western Diet-Fed Mice. Nutrients, 15.","DOI":"10.3390\/nu15030611"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41586-023-06249-4","article-title":"GDF15 promotes weight loss by enhancing energy expenditure in muscle","volume":"619","author":"Wang","year":"2023","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/0022-510X(88)90132-3","article-title":"What is the cause of the ageing atrophy?: Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15- to 83-year-old men","volume":"84","author":"Lexell","year":"1988","journal-title":"J. Neurol. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13048-018-0471-3","article-title":"Is the aging human ovary still ticking? Expression of clock-genes in luteinized granulosa cells of young and older women","volume":"11","author":"Brzezinski","year":"2018","journal-title":"J. Ovarian Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e158451","DOI":"10.1172\/JCI158451","article-title":"Metabolic changes in aging humans: Current evidence and therapeutic strategies","volume":"132","author":"Palmer","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1194\/jlr.R120000922","article-title":"Aging and plasma triglyceride metabolism","volume":"61","author":"Spitler","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Bell, K.E., Snijders, T., Zulyniak, M., Kumbhare, D., Parise, G., Chabowski, A., and Phillips, S.M. (2017). A whey protein-based multi-ingredient nutritional supplement stimulates gains in lean body mass and strength in healthy older men: A randomized controlled trial. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181387"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Nilsson, M.I., Mikhail, A., Lan, L., Di Carlo, A., Hamilton, B., Barnard, K., Hettinga, B.P., Hatcher, E., Tarnopolsky, M.G., and Nederveen, J.P. (2020). A Five-Ingredient Nutritional Supplement and Home-Based Resistance Exercise Improve Lean Mass and Strength in Free-Living Elderly. Nutrients, 12.","DOI":"10.3390\/nu12082391"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Melov, S., Tarnopolsky, M.A., Beckman, K., Felkey, K., and Hubbard, A. (2007). Resistance exercise reverses aging in human skeletal muscle. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000465"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Nederveen, J.P., Manta, K., Bujak, A.L., Simone, A.C., Fuda, M.R., Nilsson, M.I., Hettinga, B.P., Hughes, M.C., Perry, C.G.R., and Tarnopolsky, M.A. (2021). A Novel Multi-Ingredient Supplement Activates a Browning Program in White Adipose Tissue and Mitigates Weight Gain in High-Fat Diet-Fed Mice. Nutrients, 13.","DOI":"10.3390\/nu13113726"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Platko, K., Lebeau, P.F., Nederveen, J.P., Byun, J.H., MacDonald, M.E., Bourgeois, J.M., Tarnopolsky, M.A., and Austin, R.C. (2023). A Metabolic Enhancer Protects against Diet-Induced Obesity and Liver Steatosis and Corrects a Pro-Atherogenic Serum Profile in Mice. Nutrients, 15.","DOI":"10.3390\/nu15102410"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Xhuti, D., Rebalka, I.A., Minhas, M., May, L., Murphy, K., Nederveen, J.P., and Tarnopolsky, M.A. (2023). The Acute Effect of Multi-Ingredient Antioxidant Supplementation following Ionizing Radiation. Nutrients, 15.","DOI":"10.3390\/nu15010207"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1212\/01.WNL.0000125178.18862.9D","article-title":"Creatine monohydrate enhances strength and body composition in Duchenne muscular dystrophy","volume":"62","author":"Tarnopolsky","year":"2004","journal-title":"Neurology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/mus.20688","article-title":"Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders","volume":"35","author":"Rodriguez","year":"2007","journal-title":"Muscle Nerve"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/j.addr.2008.05.001","article-title":"The mitochondrial cocktail: Rationale for combined nutraceutical therapy in mitochondrial cytopathies","volume":"60","author":"Tarnopolsky","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41392-024-01839-8","article-title":"Mitochondrial dysfunction: Mechanisms and advances in therapy","volume":"9","author":"Zong","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Centonze, M., Aloisio Caruso, E., De Nunzio, V., Cofano, M., Saponara, I., Pinto, G., and Notarnicola, M. (2025). The Antiaging Potential of Dietary Plant-Based Polyphenols: A Review on Their Role in Cellular Senescence Modulation. Nutrients, 17.","DOI":"10.3390\/nu17101716"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"102733","DOI":"10.1016\/j.arr.2025.102733","article-title":"Dietary polyphenols as geroprotective compounds: From Blue Zones to hallmarks of ageing","volume":"108","author":"Davinelli","year":"2025","journal-title":"Ageing Res. Rev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.arr.2016.07.004","article-title":"Targeting mTOR signaling by polyphenols: A new therapeutic target for ageing","volume":"31","author":"Amani","year":"2016","journal-title":"Ageing Res. Rev."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1039\/D2FO02688K","article-title":"Targeting AMPK signaling by polyphenols: A novel strategy for tackling aging","volume":"14","author":"Xu","year":"2023","journal-title":"Food Funct."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1002\/ptr.5583","article-title":"A Review of Natural Stimulant and Non-stimulant Thermogenic Agents","volume":"30","author":"Stohs","year":"2016","journal-title":"Phytother. Res. PTR"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Watanabe, M., Risi, R., Masi, D., Caputi, A., Balena, A., Rossini, G., Tuccinardi, D., Mariani, S., Basciani, S., and Manfrini, S. (2020). Current Evidence to Propose Different Food Supplements for Weight Loss: A Comprehensive Review. Nutrients, 12.","DOI":"10.3390\/nu12092873"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e026756","DOI":"10.1136\/bmjopen-2018-026756","article-title":"Creatine and pregnancy outcomes, a prospective cohort study in low-risk pregnant women: Study protocol","volume":"9","author":"Ellery","year":"2019","journal-title":"BMJ Open"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Cieri-Hutcherson, N.E., Jaenecke, A., Bahia, A., Lucas, D., Oluloro, A., Stimmel, L., and Hutcherson, T.C. (2021). Systematic Review of l-Arginine for the Treatment of Hypoactive Sexual Desire Disorder and Related Conditions in Women. Pharmacy, 9.","DOI":"10.3390\/pharmacy9020071"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Goto, E. (2021). Effects of prenatal oral l-arginine on birth outcomes: A meta-analysis. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-02182-6"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2217465","DOI":"10.1080\/14767058.2023.2217465","article-title":"L-Arginine supplementation in pregnancy: A systematic review of maternal and fetal outcomes","volume":"36","author":"Menichini","year":"2023","journal-title":"J. Matern. Neonatal Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/s41366-018-0143-9","article-title":"Overfed but undernourished: Recognizing nutritional inadequacies\/deficiencies in patients with overweight or obesity","volume":"43","author":"Astrup","year":"2019","journal-title":"Int. J. Obes."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.lfs.2015.10.025","article-title":"Men and mice: Relating their ages","volume":"152","author":"Dutta","year":"2016","journal-title":"Life Sci."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/9\/1258\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:36:01Z","timestamp":1760034961000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/9\/1258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,30]]},"references-count":110,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["biom15091258"],"URL":"https:\/\/doi.org\/10.3390\/biom15091258","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,30]]}}}