Skip to main content

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

  • Hanieh Malmir (a1) (a2), Sakineh Shab-Bidar (a2) and Kurosh Djafarian (a3)

We aimed to systematically review available data on the association between vitamin C intake and bone mineral density (BMD), as well as risk of fractures and osteoporosis, and to summarise this information through a meta-analysis. Previous studies on vitamin C intake in relation to BMD and risk of fracture and osteoporosis were selected through searching PubMed, Scopus, ISI Web of Science and Google Scholar databases before February 2017, using MeSH and text words. To pool data, either a fixed-effects model or a random-effects model was used, and for assessing heterogeneity, Cochran’s Q and I 2 tests were used. Subgroup analysis was applied to define possible sources of heterogeneity. Greater dietary vitamin C intake was positively associated with BMD at femoral neck (pooled r 0·18; 0·06, 0·30) and lumbar spine (pooled r 0·14; 95 % CI 0·06, 0·22); however, significant between-study heterogeneity was found at femoral neck: I 2=87·6 %, P heterogeneity<0·001. In addition, we found a non-significant association between dietary vitamin C intake and the risk of hip fracture (overall relative risk=0·74; 95 % CI 0·51, 1·08). Significant between-study heterogeneity was found (I 2=79·1 %, P heterogeneity<0·001), and subgroup analysis indicated that study design, sex and age were the main sources of heterogeneity. Greater dietary vitamin C intake was associated with a 33 % lower risk of osteoporosis (overall relative risk=0·67; 95 % CI 0·47, 0·94). Greater dietary vitamin C intake was associated with a lower risk of hip fracture and osteoporosis, as well as higher BMD, at femoral neck and lumbar spine.

Corresponding author
* Corresponding author: S. Shab-Bidar, fax +98 21 88984861, email
Hide All
1. National Institutes of Health (NIH) Osteoporosis and Related Bone Diseases National Resource Center (2015) Osteoporosis overview. Bethesda, MD: NIH. (accessed March 2018).
2. Kanis, JA, Melton, LJ 3rd, Christiansen, C, et al. (1994) The diagnosis of osteoporosis. J Bone Miner Res 9, 11371141.
3. World Health Organization (1994) Assessment of Fracture Risk and its Application to Screening for Postmenopausal Osteoporosis. Report of a WHO Study Group. WHO Technical Report Series, no. 843. Geneva: WHO.
4. Johnell, O & Kanis, JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17, 17261733.
5. Becker, DJ, Kilgore, ML & Morrisey, MA (2010) The societal burden of osteoporosis. Curr Rheumatol Rep 12, 186191.
6. Liem, IS, Kammerlander, C, Suhm, N, et al. (2014) Literature review of outcome parameters used in studies of Geriatric Fracture Centers. Arch Orthop Trauma Surg 134, 181187.
7. Richmond, J, Aharonoff, GB, Zuckerman, JD, et al. (2003) Mortality risk after hip fracture. J Orthop Trauma 17, 5356.
8. Anagnostis, P, Karagiannis, A, Kakafika, AI, et al. (2009) Atherosclerosis and osteoporosis: age-dependent degenerative processes or related entities? Osteoporos Int 20, 197207.
9. Bollet, AJ, Engh, G & Parson, W (1965) Epidemiology of osteoporosis; sex and race incidence of hip fractures. Arch Intern Med 116, 191194.
10. Melton, LJ 3rd (2003) Epidemiology worldwide. Endocrinol Metab Clin North Am 32, 113.
11. Raisz, LG (2005) Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 115, 33183325.
12. Ojo, F, Al Snih, S, Ray, LA, et al. (2007) History of fractures as predictor of subsequent hip and nonhip fractures among older Mexican Americans. J Natl Med Assoc 99, 412418.
13. Simonelli, C, Cohan, D, Kopher, R, et al. (2006) Health Care Guideline: Diagnosis and Treatment of Osteoporosis, 5th ed. Bloomington, MN: Institute for Clinical Systems Improvement.
14. Wong, PK, Christie, JJ & Wark, JD (2007) The effects of smoking on bone health. Clin Sci (Lond) 113, 233241.
15. Berg, KM, Kunins, HV, Jackson, JL, et al. (2008) Association between alcohol consumption and both osteoporotic fracture and bone density. Am J Med 121, 406418.
16. Ilich, JZ & Kerstetter, JE (2000) Nutrition in bone health revisited: a story beyond calcium. J Am Coll Nutr 19, 715737.
17. Feskanich, D, Willett, WC, Stampfer, MJ, et al. (1996) Protein consumption and bone fractures in women. Am J Epidemiol 143, 472479.
18. Tucker, KL, Morita, K, Qiao, N, et al. (2006) Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: The Framingham Osteoporosis Study. Am J Clin Nutr 84, 936942.
19. Sun, LL, Li, BL, Xie, HL, et al. (2014) Associations between the dietary intake of antioxidant nutrients and the risk of hip fracture in elderly Chinese: a case-control study. Br J Nutr 112, 17061714.
20. Sahni, S, Hannan, MT, Gagnon, D, et al. (2009) Protective effect of total and supplemental vitamin C intake on the risk of hip fracture–a 17-year follow-up from the Framingham Osteoporosis Study. Osteoporos Int 20, 18531861.
21. Kim, MH & Lee, HJ (2016) Osteoporosis, vitamin C intake, and physical activity in Korean adults aged 50 years and over. J Phys Ther Sci 28, 725730.
22. Finck, H, Hart, AR, Lentjes, MAH, et al. (2015) Cross-sectional and prospective associations between dietary and plasma Vitamin C, heel bone ultrasound, and fracture risk in men and women in the European Prospective Investigation into Cancer in Norfolk cohort. Am J Clin Nutr 102, 14161424.
23. Kim, DE, Cho, SH, Park, HM, et al. (2016) Relationship between bone mineral density and dietary intake of -carotene, vitamin C, zinc and vegetables in postmenopausal Korean women: a cross-sectional study. J Int Med Res 44, 11031114.
24. Liu, ZM, Leung, J, Wong, SYS, et al. (2015) Greater fruit intake was associated with better bone mineral status among Chinese elderly men and women: results of Hong Kong Mr. Os and Ms. Os studies. J Am Med Dir Assoc 16, 309315.
25. Kim, YA, Kim, KM, Lim, S, et al. (2015) Favorable effect of dietary vitamin C on bone mineral density in postmenopausal women (KNHANES IV, 2009): discrepancies regarding skeletal sites, age, and vitamin D status. Osteoporos Int 26, 23292337.
26. Park, HM, Heo, J & Park, Y (2011) Calcium from plant sources is beneficial to lowering the risk of osteoporosis in postmenopausal Korean women. Nutr Res 31, 2732.
27. Prynne, CJ, Mishra, GD, O’Connell, MA, et al. (2006) Fruit and vegetable intakes and bone mineral status: a cross sectional study in 5 age and sex cohorts. Am J Clin Nutr 83, 14201428.
28. Ilich, JZ, Brownbill, RA & Tamborini, L (2003) Bone and nutrition in elderly women: protein, energy, and calcium as main determinants of bone mineral density. Eur J Clin Nutr 57, 554565.
29. Hall, SL & Greendale, GA (1998) The relation of dietary vitamin C intake to bone mineral density: Results from the PEPI study. Calcif Tissue Int 63, 183189.
30. Casale, M, von Hurst, PR, Beck, KL, et al. (2016) Lean mass and body fat percentage are contradictory predictors of bone mineral density in pre-menopausal pacific island women. Nutrients 8, 470481.
31. Leveille, SG, LaCroix, AZ, Koepsell, TD, et al. (1997) Dietary vitamin C and bone mineral density in postmenopausal women in Washington State, USA. J Epidemiol Community Health 51, 479485.
32. Moher, D, Liberati, A, Tetzlaff, J, et al. (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6, e1000097.
33. New, SA, Bolton-Smith, C, Grubb, DA, et al. (1997) Nutritional influences on bone mineral density: a cross-sectional study in premenopausal women. Am J Clin Nutr 65, 18311839.
34. Macdonald, HM, New, SA, Golden, MHN, et al. (2004) Nutritional associations with bone loss during the menopausal transition: evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of a detrimental effect of fatty acids. Am J Clin Nutr 79, 155165.
35. Wells, GA, Shea, B, O’Connell, D, et al. (2014) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa, Canada: Ottawa Hospital Research Institute. (accessed June 2016).
36. Egger, M, Smith, GD & Altman, DG (2008) Systematic Reviews in Health Care: Meta-Analysis in Context, 2th ed. London: BMJ Publishing Group.
37. Higgins, JP, Thompson, SG, Deeks, JJ, et al. (2003) Measuring inconsistency in meta-analyses. BMJ 327, 557560.
38. Chan, R, Woo, J & Leung, J (2011) Effects of food groups and dietary nutrients on bone loss in elderly Chinese population. J Nutr Health Aging 15, 287294.
39. Holbrook, TL, Barrett-Connor, E & Wingard, DL (1988) Dietary calcium and risk of hip fracture: 14-year prospective population study. Lancet ii, 10461049.
40. Key, TJ, Appleby, PN, Spencer, EA, et al. (2007) Calcium, diet and fracture risk: a prospective study of 1898 incident fractures among 34696 British women and men. Public Health Nutr 10, 13141320.
41. Samieri, C, Ginder Coupez, V, Lorrain, S, et al. (2013) Nutrient patterns and risk of fracture in older subjects: results from the Three-City Study. Osteoporos Int 24, 12951305.
42. Simon, JA & Hudes, ES (2001) Relation of ascorbic acid to bone mineral density and self-reported fractures among US adults. Am J Epidemiol 154, 427433.
43. Sugiura, M, Nakamura, M, Ogawa, K, et al. (2016) High vitamin C intake with high serum beta-cryptoxanthin associated with lower risk for osteoporosis in post-menopausal Japanese female subjects: Mikkabi cohort study. J Nutr Sci Vitaminol 62, 185191.
44. White, SC, Atchison, KA, Gornbein, JA, et al. (2006) Risk factors for fractures in older men and women: The Leisure World Cohort Study. Gend Med 3, 110123.
45. Lumbers, M, New, SA, Gibson, S, et al. (2001) Nutritional status in elderly female hip fracture patients: comparison with an age-matched home living group attending day centres. Br J Nutr 85, 733740.
46. Martínez-Ramírez, MJ, Pérez, SP, Delgado-Martínez, AD, et al. (2007) Vitamin C, vitamin B12, folate and the risk of osteoporotic fractures. A case–control study. Int J Vitam Nutr Res 77, 359368.
47. Michaelsson, K, Holmberg, L, Mallmin, H, et al. (1995) Diet and hip fracture risk: a case–control study. Study Group of the Multiple Risk Survey on Swedish Women for Eating Assessment. Int J Epidemiol 24, 771782.
48. Nieves, JW, Grisso, JA & Kelsey, JL (1992) A case-control study of hip fracture: evaluation of selected dietary variables and teenage physical activity. Osteoporos Int 2, 122127.
49. Zhang, J, Munger, RG, West, NA, et al. (2006) Antioxidant intake and risk of osteoporotic hip fracture in Utah: an effect modified by smoking status. Am J Epidemiol 163, 917.
50. Hernández-Avila, M, Stampfer, MJ, Ravnikar, VA, et al. (1992) Caffeine and other predictors of bone density among pre- and perimenopausal women. Epidemiology 4, 128134.
51. Kaptoge, S, Welch, A, McTaggart, A, et al. (2003) Effects of dietary nutrients and food groups on bone loss from the proximal femur in men and women in the 7th and 8th decades of age. Osteoporos Int 14, 418428.
52. Morton, DJ, Barrett-Connor, EL & Schneider, DL (2001) Vitamin C supplement use and bone mineral density in postmenopausal women. J Bone Miner Res 16, 135140.
53. New, SA, Robins, SP, Campbell, MK, et al. (2000) Dietary influences on bone mass and bone metabolism: Further evidence of a positive link between fruit and vegetable consumption and bone health? Am J Clin Nutr 71, 142151.
54. Rivas, A, Romero, A, Mariscal-Arcas, M, et al. (2012) Association between dietary antioxidant quality score (DAQs) and bone mineral density in Spanish women. Nutr Hosp 27, 18861893.
55. Sahni, S, Hannan, MT, Gagnon, D, et al. (2008) High vitamin C intake is associated with lower 4-year bone loss in elderly men. J Nutr 138, 19311938.
56. Sasaki, S & Yanagibori, R (2001) Association between current nutrient intakes and bone mineral density at calcaneus in pre- and postmenopausal Japanese women. J Nutr Sci Vitaminol 47, 289294.
57. Sugiura, M, Nakamura, M, Ogawa, K, et al. (2011) Dietary patterns of antioxidant vitamin and carotenoid intake associated with bone mineral density: Findings from post-menopausal Japanese female subjects. Osteoporos Int 22, 143152.
58. Wang, MC, Villa, ML, Marcus, R, et al. (1997) Associations of vitamin C, calcium and protein with bone mass in postmenopausal Mexican American women. Osteoporos Int 7, 533538.
59. Wolf, RL, Cauley, JA, Pettinger, M, et al. (2005) Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women’s Health Initiative. Am J Clin Nutr 82, 581588.
60. Yang, YJ & Kim, J (2014) Factors in relation to bone mineral density in korean middle-aged and older men: 2008–2010 Korea National Health and Nutrition Examination Survey. Ann Nutr Metab 64, 5059.
61. Zhang, J, Zhang, K, Shi, H, et al. (2015) A cross-sectional study to evaluate the associations between hypertension and osteoporosis in Chinese postmenopausal women. Int J Clin Exp Med 8, 2119421200.
62. Liu, K, Liu, P, Liu, R, et al. (2015) Relationship between serum leptin levels and bone mineral density: a systematic review and meta-analysis. Clin Chim Acta 444, 260263.
63. Melton, LJ, Kearns, AE, Atkinson, EJ, et al. (2009) Secular trends in hip fracture incidence and recurrence. Osteoporos Int 20, 687694.
64. Carinci, F, Pezzetti, F, Spina, AM, et al. (2005) Effect of Vitamin C on pre-osteoblast gene expression. Arch Oral Biol 50, 481496.
65. Harada, S, Matsumoto, T & Ogata, E (1991) Role of ascorbic acid in the regulation of proliferation in osteoblast-like MC3T3-E1 cells. J Bone Miner Res 6, 903908.
66. Chan, D, Lamande, SR, Cole, WG, et al. (1990) Regulation of procollagen synthesis and processing during ascorbate-induced extracellular matrix accumulation in vitro. Biochem J 269, 175181.
67. Barnes, MJ (1975) Function of ascorbic acid in collagen metabolism. Ann N Y Acad Sci 258, 264277.
68. Hie, M & Tsukamoto, I (2011) Vitamin C-deficiency stimulates osteoclastogenesis with an increase in RANK expression. J Nutr Biochem 22, 164171.
69. Le Nihouannen, D, Barralet, JE, Fong, JE, et al. (2010) Ascorbic acid accelerates osteoclast formation and death. Bone 46, 13361343.
70. Aghajanian, P, Hall, S, Wongworawat, MD, et al. (2015) The roles and mechanisms of actions of vitamin C in bone: new developments. J Bone Miner Res 30, 19451955.
71. Ward, KA, Prentic, A, Kuh, DL, et al. (2016) Life course dietary patterns and bone health in later life in a British Birth Cohort Study. J Bone Miner Res 31, 11671176.
72. Sahni, S, Mangano, KM, McLean, RR, et al. (2015) Dietary approaches for bone health: lessons from the Framingham Osteoporosis Study. Curr Osteoporos Rep 13, 245255.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 9
Total number of PDF views: 41 *
Loading metrics...

Abstract views

Total abstract views: 817 *
Loading metrics...

* Views captured on Cambridge Core between 12th April 2018 - 22nd April 2018. This data will be updated every 24 hours.