Nutraceuticals are essential food constituents that provide nutritional benefits as well as medicinal effects. The benefits of these foods are due to the presence of active compounds such as carotenoids, collagen hydrolysate, and dietary fibers. Nutraceuticals have been found to positively affect cardiovascular and immune system health and have a role in infection and cancer prevention. Nutraceuticals can be categorized into different classes based on their nature and mode of action. Synthetic vitamins are a booming industry, but their benefits are limited due to the general nature of the chemicals. Hypothesis: In this study, we compared different synthetic vitamins to nutraceuticals (GrandFusion, GF) and their potential therapeutic activity. Methods: Daily administration of GF diets (2%) compared to a one a day vitamin over a period of 4-months in C57BL6 mice increased mitochondrial DNA and general mitochondrial enzyme activity and enhanced mitochondrial mRNA synthesis compared to synthetic vitamin supplementation. Compared to the synthetic vitamins, all GF diets augmented mRNA expression of mitochondrial biogenesis constituents, including peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (Tfam), estrogen-related receptor alpha (ERRα), nuclear respiratory factor 1 (NRF-1), cytochrome c oxidase IV (COXIV) and ATP synthase (ATPsyn). Keyfindings: Mice treated with GF diets showed an increase in running behavioral parameters when compared to control and synthetic vitamin treated mice. GF diets enhanced protein expression of cell signaling elements including AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), PGC-1α and peroxisome proliferator-activated receptor gamma (PPAR-g), compared to synthetic vitamins. Finally, GF diets reduced autophagy and the expression of phosphorylated ribosomal protein S6 kinase 1 (p-S6K1). Conclusions: These results suggest that GF diets are more effective in improving baseline metabolic pathways compared to synthetic vitamins.
References
[1]
Dwyer, J.T., Coates, P.M. and Smith, M.J. (2018) Dietary Supplements: Regulatory Challenges and Research Resources. Nutrients, 10, Article No. 41. https://doi.org/10.3390/nu10010041
[2]
Ronis, M.J.J., Pedersen, K.B. and Watt, J. (2018) Adverse Effects of Nutraceuticals and Dietary Supplements. AnnualReviewofPharmacologyandToxicology, 58, 583-601. https://doi.org/10.1146/annurev-pharmtox-010617-052844
[3]
Reider, C.A., Chung, R., Devarshi, P.P., Grant, R.W. and Hazels Mitmesser, S. (2020) Inadequacy of Immune Health Nutrients: Intakes in US Adults, the 2005-2016 NHANES. Nutrients, 12, Article No. 1735. https://doi.org/10.3390/nu12061735
[4]
Marra, M.V. and Bailey, R.L. (2018) Position of the Academy of Nutrition and Dietetics: Micronutrient Supplementation. JournaloftheAcademyofNutritionandDietetics, 118, 2162-2173. https://doi.org/10.1016/j.jand.2018.07.022
[5]
Are Those Synthetic Vitamins Doing More Harm than Good? https://organicconsumers.org/article_24626/
Clement, B. (2005) Nutri-Con: The Truth about Vitamins & Supplements. The Vitamin Myth Exposed.
[8]
Thiel, R.J. (2000) Natural Vitamins May Be Superior to Synthetic Ones. MedicalHypotheses, 55, 461-469. https://doi.org/10.1054/mehy.2000.1090
[9]
Hamishehkar, H., Ranjdoost, F., Asgharian, P., Mahmoodpoor, A. and Sanaie, S. (2016) Vitamins, Are They Safe? AdvancedPharmaceuticalBulletin, 6, 467-477. https://doi.org/10.15171/apb.2016.061
[10]
Cheng, K., Niu, Y., Zheng, X.C., Zhang, H., Chen, Y.P., Zhang, M., et al. (2016) A Comparison of Natural (D-alpha-Tocopherol) and Synthetic (DL-alpha-Tocopherol Acetate) Vitamin E Supplementation on the Growth Performance, Meat Quality and Oxidative Status of Broilers. Asian-AustralasianJournalofAnimalSciences, 29, 681-688. https://doi.org/10.5713/ajas.15.0819
[11]
Jiang, Q. (2014) Natural Forms of Vitamin E: Metabolism, Antioxidant, and Anti-Inflammatory Activities and Their Role in Disease Prevention and Therapy. FreeRadicalBiologyandMedicine, 72, 76-90. https://doi.org/10.1016/j.freeradbiomed.2014.03.035
[12]
Jiang, Q. (2022) Metabolism of Natural Forms of Vitamin E and Biological Actions of Vitamin E Metabolites. FreeRadicalBiologyandMedicine, 179, 375-387. https://doi.org/10.1016/j.freeradbiomed.2021.11.012
[13]
Albahrani, A.A. and Greaves, R.F. (2016) Fat-Soluble Vitamins: Clinical Indications and Current Challenges for Chromatographic Measurement. The Clinical Biochemist Reviews, 37, 27-47.
[14]
Zhou, S.S. and Zhou, Y. (2014) Excess Vitamin Intake: An Unrecognized Risk Factor for Obesity. WorldJDiabetes, 5, 1-13. https://doi.org/10.4239/wjd.v5.i1.1
[15]
Yu, J., Zhu, H., Gattoni-Celli, S., Taheri, S. and Kindy, M.S. (2015) Dietary Supplementation of Grandfusion® Mitigates Cerebral Ischemia-Induced Neuronal Damage and Attenuates Inflammation. NutritionalNeuroscience, 19, 290-300. https://doi.org/10.1179/1476830515y.0000000021
[16]
Yu, J., Zhu, H., Taheri, S., Mondy, W., Perry, S., Kirstein, C., et al. (2020) Effects of Grandfusion Diet on Cognitive Impairment in Transgenic Mouse Model of Alzheimer’s Disease. Nutrients, 13, Article No. 117. https://doi.org/10.3390/nu13010117
[17]
Yu, J., Zhu, H., Taheri, S., Monday, W.L., Perry, S. and Kindy, M. (2019) Reduced Neuroinflammation and Improved Functional Recovery after Traumatic Brain Injury by Prophylactic Diet Supplementation in Mice. Nutrients, 11, Article No. 299. https://doi.org/10.3390/nu11020299
[18]
Yu, J., Zhu, H., Perry, S., Taheri, S. and Kindy, M.S. (2017) Daily Supplementation with Grandfusion® Improves Memory and Learning in Aged Rats. Aging, 9, 1041-1054. https://doi.org/10.18632/aging.101209
[19]
Yu, J., Zhu, H., Taheri, S., Perry, S. and Kindy, M.S. (2018) The Effect of Diet on Improved Endurance in Male C57BL/6 Mice. Nutrients, 10, Article No. 1101. https://doi.org/10.3390/nu10081101
[20]
Yu, J., Zhu, H., Taheri, S., Mondy, W., Perry, S. and Kindy, M.S. (2021) Plant-Based Nutritional Supplementation Attenuates LPS-Induced Low-Grade Systemic Activation. InternationalJournalofMolecularSciences, 22, Article No. 573. https://doi.org/10.3390/ijms22020573
[21]
Kim, T., Kim, M., Kim, C., Jung, H. and Hwang, J. (2016) Standardized Boesenbergiapandurata Extract Stimulates Exercise Endurance through Increasing Mitochondrial Biogenesis. JournalofMedicinalFood, 19, 692-700. https://doi.org/10.1089/jmf.2015.3630
[22]
Jaspers, R.T., Zillikens, M.C., Friesema, E.C.H., delli Paoli, G., Bloch, W., Uitterlinden, A.G., et al. (2016) Exercise, Fasting, and Mimetics: Toward Beneficial Combinations? TheFASEBJournal, 31, 14-28. https://doi.org/10.1096/fj.201600652r
[23]
Mankowski, R.T., Anton, S.D., Buford, T.W. and Leeuwenburgh, C. (2015) Dietary Antioxidants as Modifiers of Physiologic Adaptations to Exercise. Medicine&ScienceinSports&Exercise, 47, 1857-1868. https://doi.org/10.1249/mss.0000000000000620
[24]
Holloway, G.P. (2017) Nutrition and Training Influences on the Regulation of Mitochondrial Adenosine Diphosphate Sensitivity and Bioenergetics. SportsMedicine, 47, 13-21. https://doi.org/10.1007/s40279-017-0693-3
[25]
Inoue, A., Cheng, X.W., Huang, Z., Hu, L., Kikuchi, R., Jiang, H., et al. (2016) Exercise Restores Muscle Stem Cell Mobilization, Regenerative Capacity and Muscle Metabolic Alterations via Adiponectin/adipor1 Activation in SAMP10 Mice. JournalofCachexia, SarcopeniaandMuscle, 8, 370-385. https://doi.org/10.1002/jcsm.12166
[26]
Piao, L., Yu, C., Xu, W., Inoue, A., Shibata, R., Li, X., et al. (2018) Adiponectin/AdiopR1 Signal Inactivation Contributes to Impaired Angiogenesis in Mice of Advanced Age. InternationalJournalofCardiology, 267, 150-155. https://doi.org/10.1016/j.ijcard.2018.05.089
[27]
Kokkinos, P. (2012) Physical Activity, Health Benefits, and Mortality Risk. ISRNCardiology, 2012, Article ID: 718789. https://doi.org/10.5402/2012/718789
[28]
Menshikova, E.V., Ritov, V.B., Fairfull, L., Ferrell, R.E., Kelley, D.E. and Goodpaster, B.H. (2006) Effects of Exercise on Mitochondrial Content and Function in Aging Human Skeletal Muscle. TheJournalsofGerontologySeriesA: BiologicalSciencesandMedicalSciences, 61, 534-540. https://doi.org/10.1093/gerona/61.6.534
[29]
Talbot, J. and Maves, L. (2016) Skeletal Muscle Fiber Type: Using Insights from Muscle Developmental Biology to Dissect Targets for Susceptibility and Resistance to Muscle Disease. WIREsDevelopmentalBiology, 5, 518-534. https://doi.org/10.1002/wdev.230
[30]
Deane, C.S., Wilkinson, D.J., Phillips, B.E., Smith, K., Etheridge, T. and Atherton, P.J. (2017) “Nutraceuticals” in Relation to Human Skeletal Muscle and Exercise. AmericanJournalofPhysiology-EndocrinologyandMetabolism, 312, E282-E299. https://doi.org/10.1152/ajpendo.00230.2016
[31]
Sung, M.M., Byrne, N.J., Robertson, I.M., Kim, T.T., Samokhvalov, V., Levasseur, J., et al. (2017) Resveratrol Improves Exercise Performance and Skeletal Muscle Oxidative Capacity in Heart Failure. AmericanJournalofPhysiology-HeartandCirculatoryPhysiology, 312, H842-H853. https://doi.org/10.1152/ajpheart.00455.2016
[32]
Southern, W.M., Nichenko, A.S., Shill, D.D., Spencer, C.C., Jenkins, N.T., McCully, K.K., et al. (2017) Skeletal Muscle Metabolic Adaptations to Endurance Exercise Training Are Attainable in Mice with Simvastatin Treatment. PLOSONE, 12, e0172551. https://doi.org/10.1371/journal.pone.0172551
[33]
Mitsuishi, M., Miyashita, K., Muraki, A., Tamaki, M., Tanaka, K. and Itoh, H. (2013) Dietary Protein Decreases Exercise Endurance through Rapamycin-Sensitive Suppression of Muscle Mitochondria. AmericanJournalofPhysiology-EndocrinologyandMetabolism, 305, E776-E784. https://doi.org/10.1152/ajpendo.00145.2013
[34]
Ziso, D., Chun, O.K. and Puglisi, M.J. (2022) Increasing Access to Healthy Foods through Improving Food Environment: A Review of Mixed Methods Intervention Studies with Residents of Low-Income Communities. Nutrients, 14, Article No. 2278. https://doi.org/10.3390/nu14112278
[35]
Bhardwaj, R.L., Parashar, A., Parewa, H.P. and Vyas, L. (2024) An Alarming Decline in the Nutritional Quality of Foods: The Biggest Challenge for Future Generations’ Health. Foods, 13, Article No. 877. https://doi.org/10.3390/foods13060877
[36]
Owino, V., Kumwenda, C., Ekesa, B., Parker, M.E., Ewoldt, L., Roos, N., et al. (2022) The Impact of Climate Change on Food Systems, Diet Quality, Nutrition, and Health Outcomes: A Narrative Review. FrontiersinClimate, 4, 1-10. https://doi.org/10.3389/fclim.2022.941842
[37]
Lane, M.M., Gamage, E., Du, S., Ashtree, D.N., McGuinness, A.J., Gauci, S., et al. (2024) Ultra-Processed Food Exposure and Adverse Health Outcomes: Umbrella Review of Epidemiological Meta-Analyses. BMJ, 384, e077310. https://doi.org/10.1136/bmj-2023-077310
[38]
Albuquerque, T.G., Bragotto, A.P.A. and Costa, H.S. (2022) Processed Food: Nutrition, Safety, and Public Health. InternationalJournalofEnvironmentalResearchandPublicHealth, 19, Article No. 16410. https://doi.org/10.3390/ijerph192416410
[39]
Carr, A.C. and Vissers, M.C. (2013) Synthetic or Food-Derived Vitamin C—Are They Equally Bioavailable? Nutrients, 5, 4284-4304. https://doi.org/10.3390/nu5114284
[40]
Kioukia-Fougia, N., Georgiadis, N., Tsarouhas, K., Vasilaki, F., Fragiadaki, P., Meimeti, E., et al. (2017) Synthetic and Natural Nutritional Supplements: Health “Allies” or Risks to Public Health? RecentPatentsonInflammation&AllergyDrugDiscovery, 10, 72-85. https://doi.org/10.2174/1872213x10666160923163700
[41]
Tardy, A., Pouteau, E., Marquez, D., Yilmaz, C. and Scholey, A. (2020) Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence. Nutrients, 12, Article No. 228. https://doi.org/10.3390/nu12010228
[42]
Djaoudene, O., Romano, A., Bradai, Y.D., Zebiri, F., Ouchene, A., Yousfi, Y., et al. (2023) A Global Overview of Dietary Supplements: Regulation, Market Trends, Usage during the COVID-19 Pandemic, and Health Effects. Nutrients, 15, Article No. 3320. https://doi.org/10.3390/nu15153320
[43]
Rodrigo, R., Libuy, M., Feliu, F. and Hasson, D. (2014) Polyphenols in Disease: From Diet to Supplements. CurrentPharmaceuticalBiotechnology, 15, 304-317. https://doi.org/10.2174/138920101504140825113815
[44]
Tabibzadeh, S. (2022) Role of Autophagy in Aging: The Good, the Bad, and the Ugly. AgingCell, 22, e13753. https://doi.org/10.1111/acel.13753
