Top

BMC Complementary Medicine and Therapies

Published in:

Open Access 01-12-2021 | Biomarkers | Research article

Effects of resveratrol supplementation on bone quality: a systematic review and meta-analysis of randomized controlled trials

Authors: Qiangqiang Li, Guangpu Yang, Hongtao Xu, Shaowen Tang, Wayne Yuk-wai Lee

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

Abstract

Background

The results from clinical trials have revealed that the effects of resveratrol supplementation on bone mineral density (BMD) and bone biomarkers are inconsistent. Our objective was to determine the effects of resveratrol supplementation on BMD and serum bone biomarkers.

Methods

PubMed, Cochrane library, EMBASE, Web of science and Scopus were searched up to August 24, 2020. Two reviewers independently performed the articles search and screen according to defined selection criteria. The study quality of the randomized controlled trials (RCTs) was evaluated with the Cochrane scoring system. Heterogeneity among studies was examined by Cochrane Q test. Retrieved data were pooled after mean differences (MD) were computed between two groups for BMD and serum biomarkers. Subgroup analyses were performed to evaluate a potential difference in terms of dose of resveratrol and intervention duration. Sensitivity analysis was executed by omitting studies with imputed values in order to evaluate the influence of these studies on the overall results.

Results

Ten eligible studies involving 698 subjects were included in this meta-analysis with 401 participants receiving resveratrol and 297 receiving placebo. Supplementation of resveratrol had no statistically significant effects on areal bone mineral density (aBMD) at lumbar spine (MD: -0.02, 95% CI: − 0.05, 0.01, p = 0.26, I² = 6%), total hip BMD (MD: -0.01, 95% CI: − 0.04, 0.02, p = 0.65, I² = 0%), and whole body BMD (MD: 0.00, 95% CI: − 0.02, 0.02, p = 0.74, I² = 0%). Supplementation of resveratrol also did not result in significant change in bone serum markers, including serum alkaline phosphatase (ALP), bone alkaline phosphatase (BAP), osteocalcin (OCN), procollagen I N-terminal propeptide (PINP), C-terminal telopeptide of type I collagen (CTX) and parathyroid hormone (PTH). Subgroup analysis showed the effect of resveratrol supplementation on BMD and serum bone markers were similar in trails of different doses, intervention duration, and pathological conditions of the participants.

Conclusion

Resveratrol supplementation did not show any significant effect on BMD or serum bone markers with the current evidence. Further investigation with more well-organized multicentre randomized trial is warranted.

Available only for authorised users

Tou JC. Resveratrol supplementation affects bone acquisition and osteoporosis: Pre-clinical evidence toward translational diet therapy. BBA-Mol Basis Dis. 2015;1852(6):1186–94.

Gullberg B, et al. World-wide projections for hip fracture. Osteoporos Int. 1997;7(5):407–13. https://doi.org/10.1007/PL00004148.

Zeng Q, et al. The prevalence of osteoporosis in China, a nationwide, multicenter DXA survey. J Bone Miner Res. 2019;34(10):1789–97. https://doi.org/10.1002/jbmr.3757.

Tai V, et al. Calcium intake and bone mineral density: systematic review and meta-analysis. Bmj. 2015;351:h4183. https://doi.org/10.1136/bmj.h4183.

Chen LR, et al. Medical treatment for osteoporosis: from molecular to clinical opinions. Int J Mol Sci. 2019;20(9):2213. https://doi.org/10.3390/ijms20092213.

Silverman SL, et al. Osteonecrosis of the jaw and the role of bisphosphonates: a critical review. Am J Med. 2009;122(2):S33–45. https://doi.org/10.1016/j.amjmed.2008.12.005.

Kim SC, et al. Impact of the US Food and Drug Administration's safety-related announcements on the use of bisphosphonates after hip fracture. J Bone Miner Res. 2016;31(8):1536–40. https://doi.org/10.1002/jbmr.2832.

Davis, S, et al. A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures. Health Technol Assess. 2016. https://doi.org/10.3310/hta20780.

Lv F, et al. Denosumab or romosozumab therapy and risk of cardiovascular events in patients with primary osteoporosis: systematic review and meta-analysis. Bone. 2020;130:115121. https://doi.org/10.1016/j.bone.2019.115121.

10.

Smoliga JM, et al. Resveratrol and health–a comprehensive review of human clinical trials. Mol Nutr Food Res. 2011;55(8):1129–41. https://doi.org/10.1002/mnfr.201100143.

11.

Novelle MG, et al. Resveratrol supplementation: where are we now and where should we go? Ageing Res Rev. 2015;21:1–15. https://doi.org/10.1016/j.arr.2015.01.002.

12.

Pearson KJ, et al, Labinskyy N, et al. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008;8(2):157–68. https://doi.org/10.1016/j.cmet.2008.06.011.

13.

Feng J, et al. Protective effects of resveratrol on postmenopausal osteoporosis: regulation of SIRT1-NF-κB signaling pathway. Acta Biochim Biophys Sin. 2014;46(12):1024–33. https://doi.org/10.1093/abbs/gmu103.

14.

Zhao M, et al. The polyphenol resveratrol promotes skeletal growth in mice through a sirtuin 1-bone morphogenic protein 2 longevity axis. Br J Pharmacol. 2018;175(21):4183–92. https://doi.org/10.1111/bph.14477.

15.

Yu T, et al. Resveratrol promotes osteogenesis and alleviates osteoporosis by inhibiting p53. Aging (Albany NY). 2020;12(11):10359. https://doi.org/10.18632/aging.103262.

16.

Mizutani K, et al. Resveratrol stimulates the proliferation and differentiation of osteoblastic MC3T3-E1 cells. Biochem Biophys Res Commun. 1998;253(3):859–63. https://doi.org/10.1006/bbrc.1998.9870.

17.

He X, et al. Resveratrol prevents RANKL-induced osteoclast differentiation of murine osteoclast progenitor RAW 264.7 cells through inhibition of ROS production. Biochem Biophys Res Commun. 2010;401(3):356–62. https://doi.org/10.1016/j.bbrc.2010.09.053.

18.

Shakibaei M, et al. Resveratrol-mediated SIRT-1 interactions with p300 modulate receptor activator of NF-κB ligand (RANKL) activation of NF-κB signaling and inhibit osteoclastogenesis in bone-derived cells. J Biol Chem. 2011;286(13):11492–505. https://doi.org/10.1074/jbc.M110.198713.

19.

Bhattarai G, et al. Resveratrol prevents alveolar bone loss in an experimental rat model of periodontitis. Acta Biomater. 2016;29:398–408. https://doi.org/10.1016/j.actbio.2015.10.031.

20.

Feng YL, et al. Resveratrol prevents osteoporosis by upregulating FoxO1 transcriptional activity. Int J Mol Med. 2018;41(1):202–12. https://doi.org/10.3892/ijmm.2017.3208.

21.

Tseng PC, et al. Resveratrol promotes osteogenesis of human mesenchymal stem cells by upregulating RUNX2 gene expression via the SIRT1/FOXO3A axis. J Bone Miner Res. 2011;26(10):2552–63. https://doi.org/10.1002/jbmr.460.

22.

Zhou H, et al. Resveratrol augments the canonical Wnt signaling pathway in promoting osteoblastic differentiation of multipotent mesenchymal cells. Exp Cell Res. 2009;315(17):2953–62. https://doi.org/10.1016/j.yexcr.2009.07.030.

23.

Ornstrup MJ, et al. Resveratrol increases bone mineral density and bone alkaline phosphatase in obese men: a randomized placebo-controlled trial. J Clin Endocr Metab. 2014;99(12):4720–9. https://doi.org/10.1210/jc.2014-2799.

24.

Bo S, et al. Effects of resveratrol on bone health in type 2 diabetic patients. A double-blind randomized-controlled trial. Nutr Diabetes. 2018;8(1):1–10. https://doi.org/10.1038/s41387-018-0059-4.

25.

Wong RH, et al. Regular supplementation with resveratrol improves bone mineral density in postmenopausal women: a randomized, Placebo-Controlled Trial. J Bone Miner Res. 2020;35(11):2121-31. https://doi.org/10.1002/jbmr.4115.

26.

Asis M, et al. Effects of resveratrol supplementation on bone biomarkers: a systematic review and meta-analysis. Ann N Y Acad Sci. 2019;1457(1):92–103. https://doi.org/10.1111/nyas.14226.

27.

Moher D, et al. Reprint—preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Phys Ther. 2009;89(9):873–80. https://doi.org/10.1093/ptj/89.9.873.

28.

Higgins, JP, et al. Cochrane handbook for systematic reviews of interventions. 2nd Edition. Chichester (UK): Wiley; 2019.

29.

Winzenberg T, et al. Effects of calcium supplementation on bone density in healthy children: meta-analysis of randomised controlled trials. Bmj. 2006;333(7572):775. https://doi.org/10.1136/bmj.38950.561400.55.

30.

Anton SD, et al. Safety and metabolic outcomes of resveratrol supplementation in older adults: results of a twelve-week, placebo-controlled pilot study. Exp Gerontol. 2014;57:181–7. https://doi.org/10.1016/j.exger.2014.05.015.

31.

Hozo SP, et al. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5(1):13. https://doi.org/10.1186/1471-2288-5-13.

32.

Luo D, et al. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res. 2018;27(6):1785–805. https://doi.org/10.1177/0962280216669183.

33.

Higgins, JP, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. Bmj. 2011;343:d592. https://doi.org/10.1136/bmj.d5928.

34.

Higgins JP, et al. Measuring inconsistency in meta-analyses. Bmj. 2003;327(7414):557–60. https://doi.org/10.1136/bmj.327.7414.557.

35.

Poulsen MM, et al. Short-term resveratrol supplementation stimulates serum levels of bone-specific alkaline phosphatase in obese non-diabetic men. J Funct Foods. 2014;6:305–10. https://doi.org/10.1016/j.jff.2013.10.019.

36.

Heebøll S, et al. Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease. Scand J Gastroenterol. 2016;51(4):456–64. https://doi.org/10.3109/00365521.2015.1107620.

37.

Movahed A, et al. Antihyperglycemic effects of short term resveratrol supplementation in type 2 diabetic patients. Evid Based Complement Alternat Med. 2013;2013:1–11. https://doi.org/10.1155/2013/851267.

38.

Asghari S, et al. Effects of pharmacologic dose of resveratrol supplementation on oxidative/antioxidative status biomarkers in nonalcoholic fatty liver disease patients: a randomized, double-blind, placebo-controlled trial. Advanced pharmaceutical bulletin. 2018;8(2):307–17. https://doi.org/10.15171/apb.2018.036.

39.

Tomé-Carneiro J, et al. One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res. 2013;72:69–82. https://doi.org/10.1016/j.phrs.2013.03.011.

40.

van der Made SM, et al. Resveratrol does not influence metabolic risk markers related to cardiovascular health in overweight and slightly obese subjects: a randomized, placebo-controlled crossover trial. PLoS One. 2015;10(3):e0118393. https://doi.org/10.1371/journal.pone.0118393.

41.

Faghihzadeh F, et al. Resveratrol supplementation improves inflammatory biomarkers in patients with nonalcoholic fatty liver disease. Nutr Res. 2014;34(10):837–43. https://doi.org/10.1016/j.nutres.2014.09.005.

42.

Voduc N, et al. Effect of resveratrol on exercise capacity: a randomized placebo-controlled crossover pilot study. Appl Physiol Nutr Metab. 2014;39(10):1183–7. https://doi.org/10.1139/apnm-2013-0547.

43.

Kjær TN, et al. No beneficial effects of resveratrol on the metabolic syndrome: a randomized placebo-controlled clinical trial. J Clin Endocr Metab. 2017;102(5):1642–51. https://doi.org/10.1210/jc.2016-2160.

44.

Militaru C, et al. Oral resveratrol and calcium fructoborate supplementation in subjects with stable angina pectoris: effects on lipid profiles, inflammation markers, and quality of life. Nutrition. 2013;29(1):178–83. https://doi.org/10.1016/j.nut.2012.07.006.

45.

Theodotou M, et al. Effect of resveratrol on non-alcoholic fatty liver disease. Exp Ther Med. 2019;18(1):559–65. https://doi.org/10.3892/etm.2019.7607.

46.

Ortiz BOM, et al. Recovery of bone and muscle mass in patients with chronic kidney disease and iron overload on hemodialysis and taking combined supplementation with curcumin and resveratrol. Clin Interv Aging. 2019;14:2055–62. https://doi.org/10.2147/CIA.S223805.CrossRef

47.

Movahed A, et al. Efficacy and safety of resveratrol in type 1 diabetes patients: a two-month preliminary exploratory trial. Nutrients. 2020;12(1):161. https://doi.org/10.3390/nu12010161.

48.

Farzin L, et al. No beneficial effects of resveratrol supplementation on atherogenic risk factors in patients with nonalcoholic fatty liver disease. Int J Vitam Nutr Res. 2019. https://doi.org/10.1024/0300-9831/a000528.

49.

Ganta Radhika Reddy, S.P., et al. Antihyperglycemic effect of short term resveratrol supplementation in type II diabetes patients. Int J Pharm Anal Res. 2017;6(2).

50.

Chachay VS, et al. Resveratrol does not benefit patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2014;12(12):2092–2103. e6. https://doi.org/10.1016/j.cgh.2014.02.024.

51.

Mobasheri A, et al. Osteogenic effects of resveratrol in vitro: potential for the prevention and treatment of osteoporosis. Ann N Y Acad Sci. 2013;1290(1):59–66. https://doi.org/10.1111/nyas.12145.

52.

Gambini J, et al. Properties of resveratrol: in vitro and in vivo studies about metabolism, bioavailability, and biological effects in animal models and humans. Oxidative Med Cell Longev. 2015;2015:1–13. https://doi.org/10.1155/2015/837042.

53.

Wang P, et al. Metabolism and pharmacokinetics of resveratrol and pterostilbene. Biofactors. 2018;44(1):16–25. https://doi.org/10.1002/biof.1410.

54.

Kumar V, et al. Differential responses of trans-resveratrol on proliferation of neural progenitor cells and aged rat hippocampal neurogenesis. Sci Rep. 2016;6(1):28142. https://doi.org/10.1038/srep28142.

55.

Mattison JA, et al. Resveratrol prevents high fat/sucrose diet-induced central arterial wall inflammation and stiffening in nonhuman primates. Cell Metab. 2014;20(1):183–90. https://doi.org/10.1016/j.cmet.2014.04.018.

56.

Vitaglione P, et al. Bioavailability of trans-resveratrol from red wine in humans. Mol Nutr Food Res. 2005;49(5):495–504. https://doi.org/10.1002/mnfr.200500002.

57.

Li Y, et al. Resveratrol-conjugated poly-ε-caprolactone facilitates in vitro mineralization and in vivo bone regeneration. Acta Biomater. 2011;7(2):751–8. https://doi.org/10.1016/j.actbio.2010.09.008.

58.

Kapetanovic IM, et al. Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats. Cancer Chemother Pharmacol. 2011;68(3):593–601. https://doi.org/10.1007/s00280-010-1525-4.

59.

Uberti F, et al. Biological effects of combined resveratrol and vitamin D3 on ovarian tissue. J Ovarian Res. 2017;10(1):61. https://doi.org/10.1186/s13048-017-0357-9.

60.

Tangestani H, et al. Efficacy of vitamin D fortified foods on bone mineral density and serum bone biomarkers: A systematic review and meta-analysis of interventional studies. Crit Rev Food Sci Nutr. 2019:1–10. https://doi.org/10.1080/10408398.2018.1558172.

61.

Tsung-Rong, et al. Bone biomarker for the clinical assessment of osteoporosis: recent developments and future perspectives. Biomark Res. 2017;5(1):1-9. https://doi.org/10.1186/s40364-017-0097-4.

62.

Masrour RJ, et al. Quantification and comparison of bone-specific alkaline phosphatase with two methods in normal and paget's specimens. Caspian J Intern Med. 2012;3(3):478.

63.

Bharadwaj S, et al. Milk ribonuclease-enriched lactoferrin induces positive effects on bone turnover markers in postmenopausal women. Osteoporos Int. 2009;20(9):1603–11. https://doi.org/10.1007/s00198-009-0839-8.

64.

Krege JH, et al. PINP as a biological response marker during teriparatide treatment for osteoporosis. Osteoporos Int. 2014;25(9):2159–71. https://doi.org/10.1007/s00198-014-2646-0.

65.

Rosen HN, et al. Serum CTX: a new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Calcif Tissue Int. 2000;66(2):100–3. https://doi.org/10.1007/PL00005830.

66.

Silva BC, et al. Parathyroid hormone: anabolic and catabolic actions on the skeleton. Curr Opin Pharmacol. 2015;22:41–50. https://doi.org/10.1016/j.coph.2015.03.005.

Title: Effects of resveratrol supplementation on bone quality: a systematic review and meta-analysis of randomized controlled trials
Authors: Qiangqiang Li
Guangpu Yang
Hongtao Xu
Shaowen Tang
Wayne Yuk-wai Lee
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Biomarkers
Published in: BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-021-03381-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effects of resveratrol supplementation on bone quality: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2021

Phytochemical screening, antiobesity, antidiabetic and antimicrobial assessments of Orobanche aegyptiaca from Palestine

The enzymatic hydrolysates from deer sinew promote MC3T3-E1 cell proliferation and extracellular matrix synthesis by regulating multiple functional genes

The effect of the Verbascum Thapsus on episiotomy wound healing in nulliparous women: a randomized controlled trial

R. vesicarius L. exerts nephroprotective effect against cisplatin-induced oxidative stress

Biological evaluation of Safrole oil and Safrole oil Nanoemulgel as antioxidant, antidiabetic, antibacterial, antifungal and anticancer

Chemical profiles of the active fraction from Prinsepia utilis Royle leaves and its anti-benign prostatic hyperplasia evaluation in animal models