Nutraceuticals and their role in promoting musculoskeletal healthy aging
Keywords:
Healthy aging, antioxidants, sarcopenia, osteoporosis, nutraceuticals, inflammationAbstract
Background. Aging is a complex and gradual biological process that represents the major risk factor with respect to the development of chronic degenerative diseases, often associated with disability. Diet and nutrition, coupled with proper physical activity have a significant impact on the health status of the elderly with a decreased risk of disease being indicative of successful aging. Musculoskeletal conditions such as osteoporosis and sarcopenia are the most frequently reported disorders among the elderly community.
Methods. This study presents a systematic review of the literature on the potential benefits of several nutraceuticals in promoting healthy aging and in reducing the risk of chronic diseases in elderly individuals.
Results. Dietary components including vitamins (vitamin C, B vitamin and vitamin K) flavonoids (e.g., quercetin, anthocyanins, and isoflavones), minerals (e.g., magnesium, zinc and potassium) and other nutrients such phytoestrogens, amino acids, and omega-3 fatty acids help in slowing the aging process, which ultimately results in increased lifespan and longevity.
Conclusions. This paper highlights the key nutrients and phytochemicals of nutraceutical importance for the healthy aging of the elderly population. Although the scientific literature provides evidences of therapeutic effectiveness of nutraceuticals, more in-depth clinical investigations are needed.
References
1. Cristea M, Noja GG, Stefea P, Sala AL. The Impact of Population Aging and Public Health Support on EU Labor Markets. Int J Environ Res Public Health. 2020 Feb 24; 17(4): 1439. doi: 10.3390/ijerph17041439.
2. Zamudio-Rodríguez A, Letenneur L, Féart C, Avila-Funes JA, Amieva H, Pérès K. The disability process: is there a place for frailty? Age Ageing. 2020 Aug 24; 49(5): 764-70. doi:
10.1093/ageing/afaa031.
3. Arking R. Biology of Longevity and Aging: Pathways and Prospects. USA: Oxford University Press; 2019.
4. Kenyon CJ. The genetics of ageing. Nature. 2010 Mar 25; 464(7288): 504-12. doi: 10.1038/ nature08980.
5. Taylor MG, Carr D. Psychological Resilience and Health Among Older Adults: A Comparison of Personal Resources. J Gerontol B Psychol Sci Soc Sci. 2021 Jun 14; 76(6): 1241-50. doi:
10.1093/geronb/gbaa116.
6. Zulfiqar A, Ishaq S, Ahmed T. Anti-Oxidant Nutrients and Nutraceuticals in Aging. In: Nabavi SM, D’Onofrio G, Nabavi SF, eds. Nutrients and Nutraceuticals for Active & Health Ageing.
Singapore: Springer; 2020: 195-216. https://doi. org/10.1007/978-981-15-3552-9_9.
7. Santini A, Novellino E. To nutraceuticals and back: Rethinking a concept. Foods. 2017 Sep 5; 6(9): 74. doi: 10.3390/foods6090074.
8. Caponio GR, Lippolis T, Tutino V, et al. Nutraceuticals: Focus on Anti-Inflammatory, AntiCancer, Antioxidant Properties in Gastrointestinal Tract. Antioxidants (Basel). 2022 Jun 28; 11(7): 1274. doi: 10.3390/antiox11071274.
9. Suvarna V, Sarkar M, Chaubey P, et al. Bone health and natural products-an insight. Front Pharmacol 2018 Sep 19; 9: 981. doi: 10.3389/ fphar.2018.00981.
10. Egger M, Dickersin K, Smith GD. Problems and limitations in conducting systematic reviews. In: Egger M, Smith GD, Altman GD, Eds. Systematic Reviews in Health Care: Meta-Analysis in Context. Chapter 3. 2nd ed. London, UK: BMJ Books; 2001: 53-68.
11. Seely KD, Kotelko CA, Douglas H, Bealer B, Brooks AE. The Human Gut Microbiota: A Key Mediator of Osteoporosis and Osteogenesis. Int J Mol Sci. 2021 Aug 31; 22(17): 9452. doi:
10.3390/ijms22179452.
12. Polzonetti V, Pucciarelli S, Vincenzetti S, Polidori P. Dietary Intake of Vitamin D from Dairy Products Reduces the Risk of Osteoporosis. Nutrients. 2020 Jun 10; 12(6): 1743. doi: 10.3390/ nu12061743.
13. Lean JM, Jagger CJ, Kirstein B, Fuller K, Chambers TJ. Hydrogen Peroxide Is Essential for Estrogen-Deficiency Bone Loss and Osteoclast Formation. Endocrinology. 2005 Feb 1; 146(2): 728-35. doi: 10.1210/en.2004-1021. Epub 2004 Nov 4.
14. Smietana MJ, Arruda EM, Faulkner JA, Brooks S V, Larkin LM. Reactive oxygen species on bone mineral density and mechanics in Cu,Zn superoxide dismutase (Sod1) knockout mice. Biochem Biophys Res Commun. 2010 Dec 3; 403(1): 14-53. doi: 10.1016/j.bbrc.2010.11.006. Epub 2010 Nov 5.
15. Meščić Macan M, Gazivoda Kraljević T, RaićMalić S. Therapeutic Perspective of Vitamin C and Its Derivatives. Antioxidants (Basel). 2019 Jul 26; 8(8): 247. doi: 10.3390/antiox8080247.
16. Ilich JZ, Brownbill RA, Tamborini L. Bone and nutrition in elderly women: protein, energy, and calcium as main determinants of bone mineral density. Eur J Clin Nutr. 2003 Apr 17; 57(4): 554-65. doi: 10.1038/sj.ejcn.1601577.
17. New SA, Bolton-Smith C, Grubb DA, Reid DM. Nutritional influences on bone mineral density: a cross-sectional study in premenopausal women. Am J Clin Nutr. 1997 Jun 1; 65(6): 1831-9. doi:
10.1093/ajcn/65.6.1831.
18. Hall SL, Greendale GA. The Relation of Dietary Vitamin C Intake to Bone Mineral Density: Results from the PEPI Study. Calcif Tissue Int. 1998 Sep 1; 63(3): 183-9. doi: 10.1007/ s002239900512.
19. Roughead ZK, Kunkel ME. Effect of diet on bone matrix constituents. J Am
Coll Nutr. 1991 Jun 1; 10(3): 242-6. doi:
10.1080/07315724.1991.10718151.
20. Franceschi RT. The Role of Ascorbic Acid in Mesenchymal Differentiation. Nutr Rev. 1992 Mar 1; 50(3): 65-70. doi: 10.1111/j.1753-4887.1992.
tb01271.x.
21. Morton DJ, Barrett-Connor EL, Schneider DL. Vitamin C Supplement Use and Bone Mineral Density in Postmenopausal Women. J Bone Miner Res. 2001 Jan 1; 16(1): 135-40. doi: 10.1359/ jbmr.2001.16.1.135.
22. Leveille SG, LaCroix AZ, Koepsell TD, Beresford SA, Van Belle G, Buchner DM. Dietary vitamin C and bone mineral density in postmenopausal women in Washington State, USA. J Epidemiol Community Health. 1997 Oct 1; 51(5): 479-85. doi: 10.1136/jech.51.5.479.
23. Ruiz-Ramos M, Vargas LA, Van Der Goes TI, Cervantes-Sandoval A, Mendoza-Nunez VM. Supplementation of ascorbic acid and alpha-tocopherol is useful to preventing bone loss linked to oxidative stress in elderly. J Nutr Health Aging. 2010 May 29; 14(6): 467-72. doi:
10.1007/s12603-010-0099-5.
24. Nieves JW. Osteoporosis: the role of micronutrients. Am J Clin Nutr. 2005 May; 81(5): 1232S-1239S. doi: 10.1093/ajcn/81.5.1232.
25. Booth SL, Broe KE, Gagnon DR, et al. Vitamin K intake and bone mineral density in women and men. Am J Clin Nutr. 2003 Feb 1; 77(2): 512-6.
doi: 10.1093/ajcn/77.2.512.
26. Weber P. Vitamin K and bone health. Nutrition. 2001 Oct 1; 17(10): 880-7. doi: 10.1016/s08999007(01)00709-2.
27. Iwamoto I, Kosha S, Noguchi SI, et al. A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen–progestin therapy. Maturitas. 1999 Jan 4; 31(2): 161-4. doi: 10.1016/s0378-5122(98)00114-5.
28. Iwamoto J, Takeda T, Ichimura S. Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis. J Orthop Sci. 2000 Nov 1; 5(6): 546-51. doi: 10.1007/s007760070003.
29. Yazdanpanah N, Zillikens MC, Rivadeneira F, et al. Effect of dietary B vitamins on BMD and risk of fracture in elderly men and women: The Rotterdam Study. Bone. 2007 Dec 1; 41(6): 98794. doi: 10.1016/j.bone.2007.08.021. Epub 2007
Aug 17.
30. Massé PG, Rimnac CM, Yamauchi M, et al. Pyridoxine deficiency affects biomechanical properties of chick tibial bone. Bone. 1996 Jun 1; 18(6): 567-74. doi: 10.1016/8756-3282(96)00072-5.
31. Reynolds TM, Marshall PD, Brain AM. Hip fracture patients may be vitamin B6 deficient.
Acta Orthop Scand. 1992 Dec; 63(6): 635-8. doi:
10.1080/17453679209169725.
32. Herrmann M, Widmann T, Colaianni G, Colucci S, Zallone A, Herrmann W. Increased Osteoclast Activity in the Presence of Increased Homocysteine Concentrations. Clin Chem. 2005 Dec; 51(12): 2348-53. doi: 10.1373/ clinchem.2005.053363. Epub 2005 Sep 29.
33. Herrmann M, Peter Schmidt J, Umanskaya N, et al. The role of hyperhomocysteinemia as well as folate, vitamin B(6) and B(12) deficiencies in osteoporosis: a systematic review. Clin Chem Lab Med. 2007 Dec; 45(12): 1621-2. doi: 10.1515/CCLM.2007.362.
34. Tucker KL, Hannan MT, Chen H, Cupples LA, Wilson PW, Kiel DP. Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. Am J Clin Nutr. 1999 Apr 1; 69(4): 727-36. doi: 10.1093/ajcn/69.4.727.
35. Tranquilli AL, Lucino E, Garzetti GG, Romanini C. Calcium, phosphorus and magnesium intakes correlate with bone mineral content in postmenopausal women. Gynecol Endocrinol. 1994 Mar; 8(1): 55-8. doi: 10.3109/09513599409028459.
36. Yamaguchi M. Role of nutritional zinc in the prevention of osteoporosis. Mol Cell Biochem. 2009 Dec 25; 338(1): 241-54. doi: 10.1007/ s11010-009-0358-0. Epub 2009 Dec 25.
37. Ceylan MN, Akdas S, Yazihan N. Is Zinc an Important Trace Element on Bone-Related Diseases and Complications? A Meta-analysis and Systematic Review from Serum Level, Dietary Intake, and Supplementation Aspects. Biol Trace Elem Res. 2021 Feb; 199(2): 535-49. doi: 10.1007/s12011-020-02193-w. Epub 2020 May 25.
38. Alshehri MM, Sharifi-Rad J, Herrera-Bravo J, et al. Therapeutic Potential of Isoflavones with an Emphasis on Daidzein. Oxid Med Cell Longev. 2021 Sep 9; 2021: 6331630. doi: 10.1155/2021/6331630.
39. Słupski W, Jawień P, Nowak B. Botanicals in Postmenopausal Osteoporosis. Nutrients. 2021 May 11; 13(5): 1609. doi: 10.3390/ nu13051609.
40. Abdi F, Alimoradi Z, Haqi P, Mahdizad F. Effects of phytoestrogens on bone mineral density during the menopause transition: a systematic review of randomized, controlled trials. Climacteric. 2016 Dec; 19(6): 535-45. doi: 10.1080/13697137.2016.1238451. Epub 2016 Oct 6.
41. Kanadys W, Baraćska A, Błaszczuk A, et al. Effects of Soy Isoflavones on Biochemical Markers of Bone Metabolism in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Int J Environ Res Public Health. 2021 May 17; 18(10): 5346. doi: 10.3390/ijerph18105346.
42. Ciumćrnean L, Milaciu MV, Runcan O, et al. The Effects of Flavonoids in Cardiovascular Diseases. Molecules. 2020 Sep 21; 25(18): 4320. doi: 10.3390/molecules25184320.
43. Welch A, MacGregor A, Jennings A, Fairweather-Tait S, Spector T, Cassidy A. Habitual flavonoid intakes are positively associated with bone mineral density in women. J Bone Miner Res. 2012 Sep 1; 27(9): 1872-8. doi: 10.1002/ jbmr.1649.
44. Hardcastle AC, Aucott L, Reid DM, Macdonald HM. Associations between dietary flavonoid intakes and bone health in a scottish population. J Bone Miner Res. 2011 May; 26(5): 941-7. doi: 10.1002/jbmr.285.
45. Zhang ZQ, He LP, Liu YH, Liu J, Su YX, Chen YM. Association between dietary intake of flavonoid and bone mineral density in middle aged and elderly Chinese women and men. Osteoporos Int. 2014 Oct; 25(10): 2417-25. doi: 10.1007/ s00198-014-2763-9. Epub 2014 Jul 26.
46. Wong SK, Chin KY, Ima-Nirwana S. Quercetin as an Agent for Protecting the Bone: A Review of the Current Evidence. Int J Mol Sci. 2020 Sep 3; 21(17): 6448. doi: 10.3390/ijms21176448.
47. Woo JT, Nakagawa H, Notoya M, et al. Quercetin Suppresses Bone Resorption by Inhibiting the Differentiation and Activation of Osteoclasts. Biol Pharm Bull. 2004 Apr; 27(4): 504-9. doi: 10.1248/bpb.27.504.
48. Wattel A, Kamel S, Prouillet C, et al. Flavonoid quercetin decreases osteoclastic differentiation induced by RANKL via a mechanism involving NFćB and AP-1. J Cell Biochem. 2004 May 15; 92(2): 285-95. doi: 10.1002/jcb.20071.
49. Siddiqui JA, Sharan K, Swarnkar G, et al.
Quercetin-6-C-β-d-glucopyranoside isolated from Ulmus wallichiana planchon is more potent than quercetin in inhibiting osteoclastogenesis and mitigating ovariectomy-induced bone loss in rats. Menopause. 2011 Feb; 18(2): 198-207. doi: 10.1097/gme.0b013e3181e84e67.
50. Innes JK, Calder PC. Marine Omega-3 (N-3) Fatty Acids for Cardiovascular Health: An Update for 2020. Int J Mol Sci. 2020 Feb 18; 21(4): 1362. doi: 10.3390/ijms21041362.
51. Hay AWM, Hassam AG, Crawford MA, Stevens PA, Mawer EB, Jones FS. Essential fatty acid restriction inhibits vitamin D-dependent calcium absorption. Lipids. 1980 Apr; 15(4): 251-4. doi: 10.1007/BF02535835.
52. Farina EK, Kiel DP, Roubenoff R, Schaefer EJ, Cupples LA, Tucker KL. Dietary Intakes of Arachidonic Acid and α-Linolenic Acid Are Associated with Reduced Risk of Hip Fracture in Older Adults. J Nutr. 2011 Jun; 141(6): 114653. doi: 10.3945/jn.110.133728. Epub 2011 Apr 20.
53. Högström M, Nordström P, Nordström A. n−3 Fatty acids are positively associated with peak bone mineral density and bone accrual in healthy men: the NO2 Study. Am J Clin Nutr. 2007 Mar 1; 85(3): 803-7. doi: 10.1093/ajcn/85.3.803.
54. Rousseau JH, Kleppinger A, Kenny AM. SelfReported Dietary Intake of Omega-3 Fatty Acids and Association with Bone and Lower Extremity Function. J Am Geriatr Soc. 2009 Oct; 57(10): 1781-8. doi: 10.1111/j.1532-5415 .2008.01870.x.
55. Järvinen R, Tuppurainen M, Erkkilä AT, et al. Associations of dietary polyunsaturated fatty acids with bone mineral density in elderly women. Eur J Clin Nutr. 2011 Nov 23; 66(4): 496-503. doi: 10.1038/ejcn.2011.188. Epub 2011 Nov 23.
56. Lavado-García J, Roncero-Martin R, Moran JM, et al. Long-chain omega-3 polyunsaturated fatty acid dietary intake is positively associated with bone mineral density in normal and osteopenic Spanish women. PLoS One. 2018 Jan 5; 13(1):
e0190539. doi: 10.1371/journal.pone.0190539.
57. Kuroda T, Ohta H, Onoe Y, Tsugawa N, Shiraki M. Intake of omega-3 fatty acids contributes to bone mineral density at the hip in a younger Japanese female population. Osteoporos Int. 2017 Jun 23; 28(10): 2887-91. doi: 10.1007/ s00198-017-4128-7. Epub 2017 Jun 23.
58. Martyniak K, Wei F, Ballesteros A, et al. Do polyunsaturated fatty acids protect against bone
loss in our aging and osteoporotic population?
Bone. 2021 Feb; 143: 115736. doi: 10.1016/j.
bone.2020.115736. Epub 2020 Nov 7.
59. Orchard TS, Pan X, Cheek F, Ing SW, Jackson RD. A systematic review of omega-3 fatty acids and osteoporosis. Br J Nutr. 2012 Jun; 107(S2): S253-60. doi: 10.1017/S0007114512001638.
60. Lee K, Kim KR, Lee H, Choi S, Jang IT, Kim
H. Dietary Intake of Polyunsaturated Fatty Acids Lowers the Risk of Osteoporosis in Older Korean Females. Cent Asian J Med Sci. 2020; 6(3): 174-81. doi: https://doi.org/10.24079/ CAJMS.2020.09.010.
61. Rolland Y, Czerwinski S, van Kan GA, et al. Sarcopenia: Its assessment, etiology, pathogenesis, consequences and future perspectives. J Nutr Heal Aging. 2008 Aug-Sep; 12(7): 433-50. doi: 10.1007/BF02982704.
62. Alalwan TA. Phenotypes of Sarcopenic Obesity: Exploring the Effects on Peri-Muscular Fat, the Obesity Paradox, Hormone-Related Responses and the Clinical Implications. Geriatrics. 2020 Feb 14; 5(1): 8. doi: 10.3390/geriatrics5010008.
63. McGregor RA, Cameron-Smith D, Poppitt SD. It is not just muscle mass: a review of muscle quality, composition and metabolism during ageing as determinants of muscle function and mobility in later life. Longev Healthspan. 2014 Dec 1; 3(1): 1-8. doi: 10.1186/2046-2395-3-9.
64. Granic A, Sayer AA, Robinson SM. Dietary Patterns, Skeletal Muscle Health, and Sarcopenia in Older Adults. Nutrients. 2019 Mar 30; 11(4): 745. doi: 10.3390/nu11040745.
65. Bauer J, Biolo G, Cederholm T, et al. EvidenceBased Recommendations for Optimal Dietary Protein Intake in Older People: A Position
Paper From the PROT-AGE Study Group. J Am Med Dir Assoc. 2013 Aug; 14(8): 542-59. doi: 10.1016/j.jamda.2013.05.021. Epub 2013 Jul 16.
66. Alamdari N, O’Neal P, Hasselgren PO. Curcumin and muscle wasting—A new role for an old drug? Nutrition. 2009 Feb; 25(2): 125-9. doi: 10.1016/j.nut.2008.09.002. Epub 2008 Nov 22.
67. Hao Q, Wang HW, Yu Q, et al. [Effects of curcumin on the recovery of hind limb function after spinal cord injury in rats and its mechamism]. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2017 May 8; 33(5): 441-4. Chinese. doi: 10.12047/j. cjap.5548.2017.106.
68. Fang W, Nasir Y. The effect of curcumin supplementation on recovery following exerciseinduced muscle damage and delayed-onset muscle soreness: A systematic review and metaanalysis of randomized controlled trials. Phyther Res. 2021 Apr; 35(4): 1768-81. doi: 10.1002/ ptr.6912. Epub 2020 Nov 10.
69. Shehzad A, Lee YS. Molecular mechanisms of curcumin action: Signal transduction. BioFactors. 2013 Jan-Feb; 39(1): 27-36. doi: 10.1002/ biof.1065. Epub 2013 Jan 10.
70. Wang N, Chen Y, Ji, et al. The relationship between serum vitamin D and fracture risk in the elderly: a meta-analysis. J Orthop Surg Res. 2020 Feb 27; 15(1): 81. doi: 10.1186/s13018020-01603-y.
71. Weaver CM, Alexander DD, Boushey CJ, et al. Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporos Int. 2016 Jan; 27(1): 367-76. doi: 10.1007/ s00198-015-3386-5. Epub 2015 Oct 28.
72. Malmir H, Shab-Bidar S, Djafarian K. Vitamin C intake in relation to bone mineral density and risk of hip fracture and osteoporosis: A systematic review and meta-analysis of observational studies. Br J Nutr. 2018; 119(8): 847-58. doi:
10.1017/S0007114518000430.
73. Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Jun 26; 166(12): 1256-61. doi: 10.1001/archinte.166.12.1256.
74. He T, Jin X, Koh YS, Zhang Q, Zhang C, Liu F. The association of homocysteine, folate, vitamin B12, and vitamin B6 with fracture incidence in older adults: a systematic review and metaanalysis. Ann Transl Med. 2021 Jul; 9(14): 1143.
doi: 10.21037/atm-21-2514.
75. Zheng J, Mao X, Ling J, He Q, Quan J, Jiang H. Association between serum level of magnesium and postmenopausal osteoporosis: a meta-analysis. Biol Trace Elem Res. 2014 Jun; 159(1-3): 8-14. doi: 10.1007/s12011-014-9961-3. Epub 2014 Apr 12.
76. Lambert H, Frassetto L, Moore JB, et al. The effect of supplementation with alkaline potassium salts on bone metabolism: a meta-analysis. Osteoporos Int 2015 Apr; 26(4): 1311-8. doi: 10.1007/s00198-014-3006-9. Epub 2015 Jan 9.
77. Munguía L, Ortiz M, González C, et al. Beneficial Effects of Flavonoids on Skeletal Muscle Health: A Systematic Review and Meta-Analysis. J Med Food. 2022 May; 25(5): 465-86. doi: 10.1089/jmf.2021.0054. Epub 2022 Apr 8.
78. Bird JK, Troesch B, Warnke I, Calder PC. The effect of long chain omega-3 polyunsaturated fatty acids on muscle mass and function in sarcopenia: A scoping systematic review and meta-analysis. Clin Nutr ESPEN. 2021 Dec; 46: 73-86. doi: 10.1016/j.clnesp.2021.10.011. Epub 2021 Oct 20.
79. Jeong HY, Kwon O. Dietary phytochemicals as a promising nutritional strategy for sarcopenia: a systematic review and meta-analysis of randomized controlled trials. Appl Biol Chem. 2021 Aug 19; 64(1): 1-14. doi: https://doi.org/10.1186/ s13765-021-00633-2.
Downloads
Published
Issue
Section
License

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.