Cardiovascular calcification and bone: a comparison of the effects of dietary and serum antioxidants


  • Rachel Nicoll
  • John McLaren Howard
  • Michael Henein



Severe cardiovascular (CV) calcification can manifest as fully formed bone and is regularly found with osteoporosis; both have been shown to be associated with oxidative stress. Studies of the effect of antioxidants on CV calcification are few, but show that deficiency can induce both CV calcification and bone loss, while in conditions of oxidative stress such as renal failure, diabetes and smoking or in osteoporosis and fracture, antioxidants can reduce CV calcification and improve bone. The benefit of antioxidants in healthy adults is less clear and some may be detrimental. Higher intake of α-tocopherol (105.5mg/d vs 76.4mg/d) and β-cryptoxanthin may increase risk of CV calcification while high intake of retinol (≥3000mcg/d) may increase hip fracture risk, although possibly only with vitamin D intake ≤440IU/d; the carotenoids lycopene and β-carotene, however, appear beneficial in bone. Vitamin C shows little effect on CV calcification, although longer term supplementation may improve bone mineral density where calcium intake is >500mg/d. Potential reasons for this include a U-shaped dose/response curve for the fat-soluble antioxidants vitamins A and E (with peak bone mass achieved with retinol intake of 600–840 mcg/d), a failure to measure baseline concentrations so that the response cannot be stratified by requirement, the need to be replete in calcium and vitamin D and supplementation of the wrong isomer of vitamin E. Finally, although little studied, tocotrienols, tocopherols (with the exception of α-tocopherol), resveratrol, epigallocatechin gallate, quercetin, α-lipoic acid and N-acetylcysteine may be effective in both the CV system and bone. 


Nicoll R, Henein M. Extensive coronary calcification: a clinically unrecognised condition. Curr Vasc Pharmacol. 2010 Sep;8(5):701-5

Min H, Morony S, Sarosi I, Dunstan CR, Capparelli C, Scully S, et al. Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis. J Exp Med 2000; 192: 463-474

Hirasaka N, Liang XM, Mune M. Atherosclerosis and vascular calcification in hemodialysis patients. Clin Calcium. 2004 Jun;14(6):85-90

Tang FT, Chen SR, Wu XQ, Wang TQ, Chen JW, Li J, Bao LP, Huang HQ, Liu PQ. Hypercholesterolemia accelerates vascular calcification induced by excessive vitamin D via oxidative stress. Calcif Tissue Int. 2006 Nov;79(5):326-39

Sheweita SA, Khoshhal KI. Calcium metabolism and oxidative stress in bone fractures: role of antioxidants. Curr Drug Metab. 2007; 8: 519-525

Rhee EJ, Nallamshetty S, Plutzky J. Retinoid metabolism and its effects on the vasculature. Biochim Biophys Acta. 2012 Jan;1821(1):230-40

Filaire E Toumi H. ‘Reactive oxygen species and exercise on bone metabolism: friend or enemy?’. Joint Bone Spine. 2012; 79(4): 341-6

Ha H, Lee JH, Kim HN, Lee ZH. ‘Alpha-tocotrienol inhibits osteoclastic bone resorption by suppressing RANKL expression and signalling and bone resorbing activity’. Biochem Biophys Res Commun. 2011; 406(4): 546-51

Brzóska MM, Rogalska J. Protective effect of zinc supplementation against cadmium-induced oxidative stress and the RANK/RANKL/OPG system imbalance in the bone tissue of rats. Toxicol Appl Pharmacol. 2013 Oct 1;272(1):208-20

Chavan SN, More U, Mulgund S, Saxena V, Sontakke AN. Effect of supplementation of vitamin C and E on oxidative stress in osteoporosis. Indian J Clin Biochem. 2007 Sep;22(2):101-5

Ahmadi N, Tsimikas S, Hajsadeghi F, Saeed A, Nabavi V, Bevinal MA, Kadakia J, Flores F, Ebrahimi R, Budoff MJ. Relation of oxidative biomarkers, vascular dysfunction, and progression of coronary artery calcium. Am J Cardiol. 2010 Feb 15;105(4):459-66

Watanabe K, Ohara M, Suzuki T, Ouchi M, Suzuki K, Hashimoto M et al. ‘Aortic arch calcification detectable on chest X-ray films is associated with plasma diacron-reactive oxygen metabolites in patients with type 2 diabetes but without cardiovascular disease’. J Nippon Med Sch. 2013; 80(6): 410-9

Liberman M, Bassi E, Martinatti MK, Lario FC, Wosniak J, Pomerantzeff PM, Laurindo FR. ‘Oxidant generation predominates around calcifying foci and enhances progression of aortic valve calcification’. Atheroscler Thromb Vasc Biol. 2008; 28(3): 463-70

Muteliefu G, Enomoto A, Niwa T. Indoxyl sulfate promotes proliferation of human aortic smooth muscle cells by inducing oxidative stress. J Ren Nutr. 2009 Jan;19(1):29-32

Muteliefu G, Shimizu H, Enomoto A, Nishijima F, Takahashi M, Niwa T. ‘Indoxyl sulfate promotes vascular smooth muscle cell senescence with upregulation of p53, p21 and prelamin A through oxidative stress’. Am J Physiol Cell Physiol. 2012; 303(2): C126-34

Lalaoui MZ, el-Midaoui A, de Champlain J, Moreau P. ‘Is there a role for reactive oxygen species in arterial medial elastocalcinosis?’. Vascul Pharmacol. 2007; 46(3): 201-6

Brodeur MR, Bouvet C, Bouchard S, Moreau S, Leblond J, Deblois D, Moreau P. ‘Reduction of advanced-glycation end products levels and inhibition of RAGE signalling decreases rat vascular calcification induced by diabetes’. PLoS One. 2014; 9(1): e85922

Mody N, Parhami F, Sarafian TA, Demer LL. ‘Oxidative stress modulates osteoblastic differentiation of vascular and bone cells’. Free Radic Biol Med. 2001; 31(4): 509-19

Maziere C, Salle V, Gomila C, Maziere JC. ‘Oxidised low density lipoprotein increases RANKL level in humas vascular cells. Involvement of oxidative stress’. Biochem Biophys Res Commun. 2013; Epub ahead of print.

Liu H, Li X, Qin F, Huang K. Selenium suppresses oxidative-stress-enhanced vascular smooth muscle cell calcification by inhibiting the activation of the PI3K/AKT and ERK signaling pathways and endoplasmic reticulum stress. J Biol Inorg Chem. 2014 Jan 4. [Epub ahead of print]

Liu H, Lu Q, Huang K. Selenium suppressed hydrogen peroxide-induced vascular smooth muscle cells calcification through inhibiting oxidative stress and ERK activation. J Cell Biochem. 2010 Dec 15;111(6):1556-64

Valabhji J, McColl AJ, Richmond W, Schachter M, Rubens MB, Elkeles RS. ‘Total antioxidant status and coronary artery calcification in type 1 diabetes’. Diabetes Care. 2001; 24(9): 1608-13

Yamada S, Taniguchi M, Tokumoto M, Toyonaga J, Fujisaki K, Suehiro T et al. ‘The antioxidant tempol ameliorates arterial medial calcification in uremic rats: important role of oxidative stress in the pathogenesis of vascular calcification in chronic kidney disease’. J Bone Miner Res. 2012; 27(2): 474-85

Brooks R, Kalia P, Ireland DC, Beeton C, Rushton N. ‘Direct inhibition of osteoclast formation and activity by the vitamin E isomer γ-tocotrienol’. Int J Vitam Nutr Res. 2011; 81(6): 358-67

Liu H, Bian W, Liu S, Huang K. Selenium protects bone marrow stromal cells against hydrogen peroxide-induced inhibition of osteoblastic differentiation by suppressing oxidative stress and ERK signaling pathway. Biol Trace Elem Res. 2012 Dec;150(1-3):441-50

Iitsuka N, Hie M, Tsukamoto I. Zinc supplementation inhibits the increase in osteoclastogenesis and decrease in osteoblastogenesis in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2013 Aug 15;714(1-3):41-7

Zhu D, Mackenzie NC, Millan JL, Farquharson C, Macrae VE. ‘Upregulation of IGF2 expression during vascular calcification’. J Mol Endocrinol. 2014; 52(2): 77-85

Nojiri H, Saita Y, Morikawa D, Kobayashi K, Tsuda C, Miyazaki T et al. ‘Cytoplasmic superoxide causes bone fragility owing to low-turnover osteoporosis and impaired collagen cross-linking’. J Bone Miner Res. 2011; 26(11): 2682-94

Maggio D, Barabani M, Pierandrei M, Polidori MC, Catani M, Mecocci P et al. ‘Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study’. J Clin Endocrinol Metab. 2003;88:1523–1527

Kuyumcu ME, Yesil Y, Ozturk ZA, Cinar E, Kizilarslanoglu C, Halil M et al. ‘The association between homocysteine (hcy) and serum natural antioxidants in elderly bone mineral densitometry (BMD)’. Arch Gerontol Geriatr. 2012; 55(3): 739-43

Ostman B, Michaelsson K, Helmersson J, Byberg L, Gedeborg R, Melhus H, Basu S. ‘Oxidative stress and bone mineral density in elderly men: antioxidant activity of alpha-tocopherol’. Free Radic Biol Med. 2009; 47(5): 668-73

Nazrun AS, Norazlina M, Norliza M, Ima Nirwana S. The anti-inflammatory role of vitamin E in prevention of osteoporosis. Adv Pharmacol Sci. 2012; Epub ahead of print

Conaway HH, Henning P, Lerner UH. ‘Vitamin A metabolism, action and role in skeletal homeostasis’. Endocr Rev. 2013; Epub ahead of print

Hatzigeorgiou C, Taylor AJ, Feuerstein IM, Bautista L, O'Malley PG. Antioxidant vitamin intake and subclinical coronary atherosclerosis. Prev Cardiol. 2006 Spring;9(2):75-81

McQuillan BM, Hung J, Beilby JP, Nidorf M, Thompson PL. Antioxidant vitamins and the risk of carotid atherosclerosis. The Perth Carotid Ultrasound Disease Assessment study (CUDAS). J Am Coll Cardiol. 2001 Dec;38(7):1788-94

Iannuzzi A, Celentano E, Panico S, Galasso R, Covetti G, Sacchetti L, Zarrilli F, De Michele M, Rubba P. Dietary and circulating antioxidant vitamins in relation to carotid plaques in middle-aged women. Am J Clin Nutr. 2002 Sep;76(3):582-7

Streb JW, Miano JM. Retinoids: pleiotropic agents of therapy for vascular diseases? Curr Drug Targets Cardiovasc Haematol Disord. 2003 Mar;3(1):31-57

Huang G, Wang D, Khan UI, Zeb I, Manson JE, Miller V, Hodis HN, Budoff MJ, Merriam GR, Harman SM, Brinton EA, Cedars MI, Lobo RA, Naftolin F, Santoro N, Taylor HS, Wildman RP, Su Y. Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: Cross-sectional analyses from the KEEPS Study. Cardiovasc Diabetol. 2012 May 15;11(1):52

Huk DJ, Hammond HL, Kegechika H, Lincoln J. ‘Increased dietary intake of vitamin A promotes aortic valve calcification in vivo’. Arterioscler Thromb Vasc Biol. 2013; 33(2): 285-93

Klipstein-Grobusch K, Launer LJ, Geleijnse JM, Boeing H, Hofman A, Witteman JC. Serum carotenoids and atherosclerosis. The Rotterdam Study. Atherosclerosis. 2000 Jan;148(1):49-56

Caire-Juvera G, Ritenbaugh C, Wactawski-Wende J, Snetselaar LG, Chen Z. Vitamin A and retinol intakes and the risk of fractures among participants of the Women's Health Initiative Observational Study. Am J Clin Nutr. 2009 Jan;89(1):323-30

Wolf RL, Cauley JA, Pettinger M, Jackson R, Lacroix A, Leboff MS et al. ‘Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women’s Health Initiative’. Am J Clin Nutr. 2005; 82(3): 581-8

Rejnmark L, Vestergaard P, Charles P, et al. No effect of vitamin A intake on bone mineral density and fracture risk in perimenopausal women. Osteoporosis Int. 2004;15:872–880

Wattanapenpaiboon N, Lukito W, Wahlqvist ML, Strauss BJ. ‘Dietary carotenoid intake as a predictor of bone mineral density’. Asia Pac J Clin Nutr. 2003; 12(4): 467-73

Kaptoge S, Welch A, McTaggart A, et al. 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 life. Osteoporosis Int. 2003;14: 418–428

Feskanich D, Singh V, Willett WC, Colditz GA. Vitamin A intake and hip fractures among postmenopausal women. JAMA. 2002;287:47–54

Promislow JH, Goodman-Gruen D, Slymen DJ, Barrett-Connor E. Retinol intake and bone mineral density in the elderly: the Rancho Bernardo Study. J Bone Miner Res. 2002;17:1349–1358

Mata-Granados JM, Cuenca-Acevedo JR, Luque de Castro MD, Holick MF, Quesada-Gomez JM. ‘Vitamin D insufficiency together with high serum levels of vitamin A increases the risk for osteoporosis in postmenopausal women’. Arch Osteoporos. 2013; 8(1-2): 124

Mata-Granados JM, Cuenca-Acevedo JR, Luque de Castro MD, Sosa M, Quesada-Gomez JM. ‘Vitamin D deficiency and high serum levels of vitamin A increase the risk of osteoporosis evaluated by Quantitative Ultrasound Measurements (QUS) in postmenopausal Spanish women’. Clin Biochem. 2010; 43(13-14): 1064-8

Sahni S, Hannan MT, Blumberg J, Cupples LA, Kiel DP, Tucker KL. Inverse association of carotenoid intakes with 4-y change in bone mineral density in elderly men and women: the Framingham Osteoporosis Study. Am J Clin Nutr. 2009 Jan;89(1):416-24

Sahni S, Hannan MT, Blumberg J, Cupples LA, Kiel DP, Tucker KL. ‘Protective effect of total carotenoid and lycopene intake on the risk of hip fracture: a 17-year follow-up from the Framingham Osteoporosis Study’. J Bone Miner Res. 2009; 24(6): 1086-94

Yamaguchi M. Regulatory mechanism of food factors in bone metabolism and prevention of osteoporosis. Yakugaku Zasshi. 2006; 126(11): 1117-1137

Ambrosini GL, Bremner AP, Reid A, Mackerras D, Alfonso H, Olsen NJ et al. ‘No dose-dependent increase in fracture risk after long-term exposure to high doses of retinol or beta-carotene’. Osteoporosis Int. 2013; 24(4): 1285-93

Kawahara TN, Krueger DC, Engelke JA, Harke JM, Binkley NC. Short-term vitamin A supplementation does not affect bone turnover in men. J Nutr. 2002; 132:1169–1172

Mackinnon ES, Rao AV, Rao LG. Dietary restriction of lycopene for a period of one month resulted in significantly increased biomarkers of oxidative stress and bone resorption in postmenopausal women. J Nutr Health Aging. 2011 Feb;15(2):133-8

Nieves JW. ‘Osteoporosis: the role of micronutrients’. Am J Clin Nutr. 2005; 81(5): 1232S-1239S

Morton DJ, Barrett-Connor EL, Schneider DL. Vitamin C supplement use and bone mineral density in postmenopausal women. J Bone Miner Res. 2001 Jan;16(1):135-40

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;63(3):183-9

Zhu LL, Cao J, Sun M, Yuen T, Zhou R, Li J et al. Vitamin C prevents hypogonadal bone loss. PLoS One. 2012; 7(10): e47058

Liu H, Yuan L, Xu S, Zhang T, Wang K. Cholestane-3beta, 5alpha, 6beta-triol promotes vascular smooth muscle cells calcification. Life Sci. 2004 Dec 17;76(5):533-43

Vasudev SC, Chandy T, Sharma CP. Glutaraldehyde treated bovine pericardium: changes in calcification due to vitamins and platelet inhibitors. Artif Organs. 1997 Sep;21(9):1007-13

Lesauskaite V, Ivanoviene L, Valanciūte A. Programmed cellular death and atherogenesis: from molecular mechanisms to clinical aspects. Medicina (Kaunas). 2003;39(6):529-34

Arad Y, Spadaro LA, Roth M, Newstein D, Guerci AD. Treatment of asymptomatic adults with elevated coronary calcium scores with atorvastatin, vitamin C, and vitamin E: the St. Francis Heart Study randomized clinical trial. J Am Coll Cardiol. 2005 Jul 5;46(1):166-72

Takata T, Ikeda M, Kodama H, Kitagawa N. Treatment of pseudoxanthoma elasticum with tocopherol acetate and ascorbic acid. Pediatr Dermatol. 2007 Jul-Aug;24(4):424-5

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; 65(6): 1831-9

Sahni S, Hannan MT, Gagnon D, Blumberg J, Cupples LA, Kiel DP, Tucker KL. ‘High vitamin C intake is associated with lower 4-year bone loss in elderly men’. J Nutr. 2008; 138(10): 1931-8

Macdonald HM, New SA, Golden MH, Campbell MK, Reid DM. 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. 2004 Jan;79(1):155-65

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;51(5):479-85

Klipstein-Grobusch K, Launer LJ, Geleijnse JM, Boeing H, Hofman A, Witteman JC. Serum carotenoids and atherosclerosis. The Rotterdam Study. Atherosclerosis. 2000 Jan;148(1):49-56

Martínez-Ramírez MJ, Palma Pérez S, Delgado-Martínez AD, Martínez-González MA, De la Fuente Arrillaga C, Delgado-Rodríguez M. Vitamin C, vitamin B12, folate and the risk of osteoporotic fractures. A case-control study. Int J Vitam Nutr Res. 2007 Nov;77(6):359-68.

Melhus H, Michaelsson K, Holmberg L, Wolk A, Ljunghall S. ‘Smoking, antioxidant vitamins and the risk of hip fracture’. J Bone Miner Res. 1999; 14(1): 129-35

Zhang J, Munger RG, West NA, Cutler DR, Wengreen HJ, Corcoran CD. Antioxidant intake and risk of osteoporotic hip fracture in Utah: an effect modified by smoking status. Am J Epidemiol. 2006 Jan 1;163(1):9-17

Talaulikar VS, Chambers T, Manyonda I. Exploiting the antioxidant potential of a common vitamin: could vitamin C prevent postmenopausal osteoporosis? J Obstet Gynaecol Res. 2012 Jan;38(1):253-7

Chuin A, Labonté M, Tessier D, Khalil A, Bobeuf F, Doyon CY, Rieth N, Dionne IJ. Effect of antioxidants combined to resistance training on BMD in elderly women: a pilot study. Osteoporos Int. 2009 Jul;20(7):1253-8

Mohan S, Kapoor A, Singgih A, Zhang Z, Taylor T, Yu H, Chadwick RB, Chung YS, Donahue LR, Rosen C, Crawford GC, Wergedal J, Baylink DJ. Spontaneous fractures in the mouse mutant sfx are caused by deletion of the gulonolactone oxidase gene, causing vitamin C deficiency. J Bone Miner Res. 2005 Sep;20(9):1597-610

Hie M, Tsukamoto I. Vitamin C-deficiency stimulates osteoclastogenesis with an increase in RANK expression. J Nutr Biochem. 2011 Feb;22(2):164-71

Lean JM, Davies JT, Fuller K, Jagger CJ, Kirstein B, Partington GA, Urry ZL, Chambers TJ. A crucial role for thiol antioxidants in estrogen-deficiency bone loss. J Clin Invest. 2003 Sep;112(6):915-23

Sanbe T, Tomofuji T, Ekuni D, Azuma T, Irie K, Tamaki N, Yamamoto T, Morita M. Vitamin C intake inhibits serum lipid peroxidation and osteoclast differentiation on alveolar bone in rats fed on a high-cholesterol diet. Arch Oral Biol. 2009 Mar;54(3):235-40

Aggarwal BB, Sundaram C, Prasad S, Kannappan R. ‘Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases’. Biochem Pharmacol. 2010; 80(11): 1613-31

Naina Mohamed I, Borhanuddin B, Shuid AN, Mohd Fozi NF. ‘Vitamin E and bone structural changes: an evidence-based review’. Evid Based Complement Alternat Med. 2012; 2012: 250584

Borhanuddin B, Fozi NFM, Naina Mohamed I. Vitamin E and the healing of bone fracture: the current state of evidence. Evidence-based Complimentary and Alternative Medicine. 2012;

Son YK, Lee SM, Kim SE, Kim KH, Lee SY, Bae HR, Han JY, Park Y, An WS. Association between vascular calcification scores on plain radiographs and fatty acid contents of erythrocyte membrane in hemodialysis patients. J Ren Nutr. 2012 Jan;22(1):58-66

Mata-Granados JM, Cuenca-Acebedo R, Luque de Castro MD, Quesada Gomez JM. ‘Lower vitamin E serum levels are associated with osteoporosis in early postmenopausal women: a cross-sectional study’. J Bone Miner Metab. 2013; Epub ahead of print.

Hamidi MS, Corey PN, Cheung AM. ‘Effects of vitamin E on bone turnover markers among US postmenopausal women’. J Bone Miner Res. 2012; 27(6): 1368-80

Booth SL, Golly I, Sacheck JM, Roubenoff R, Dallal GE, Hamada K, Blumberg JB. ‘Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status’. Am J Clin Nutr. 2004; 80(1): 143-8

Chin KY, Ima-Nirwana S. Vitamin E as an antiosteoporotic agent via receptor activator of nuclear factor kappa-B ligand signalling disruption: current evidence and other potential research areas. Evid Based Complement Altern Med. 2012; Epub ahead of print.

Vogt MT, San Valentin R, Forrest KY, Nevitt MC, Cauley JA. Bone mineral density and aortic calcification: the Study of Osteoporotic Fractures. J Am Geriatr Soc. 1997 Feb;45(2):140-5.

van Woudenbergh GJ, Vliegenthart R, van Rooij FJ, Hofman A, Oudkerk M, Witteman JC, Geleijnse JM. Coffee consumption and coronary calcification: the Rotterdam Coronary Calcification Study. Arterioscler Thromb Vasc Biol. 2008 May;28(5):1018-23.

Rehman H, Krishnasamy Y, Haque K, Thurman RG, Lemasters JJ, Schnellmann RG, Zhong Z. Green tea polyphenols stimulate mitochondrial biogenesis and improve renal function after chronic cyclosporin a treatment in rats. PLoS One. 2013 Jun 3;8(6):e65029.

Konoplyannikov M, Nurminskaya M. New Therapeutic Approaches to Arterial Calcification Via Inhibition of Transglutaminase and B-Catenin Signaling. Curr Pharm Des. 2014 Feb 12. [Epub ahead of print]

Beazley KE, Lima F, Borras T, Nurminskaya M. Attenuation of chondrogenic transformation in vascular smooth muscle by dietary quercetin in the MGP-deficient mouse model. PLoS One. 2013 Sep 30;8(9):e76210

Beazley KE, Eghtesad S, Nurminskaya MV. Quercetin attenuates warfarin-induced vascular calcification in vitro independently from matrix Gla protein. J Biol Chem. 2013 Jan 25;288(4):2632-40

Zhai W, Lü X, Chang J, Zhou Y, Zhang H. Quercetin-crosslinked porcine heart valve matrix: mechanical properties, stability, anticalcification and cytocompatibility. Acta Biomater. 2010 Feb;6(2):389-95

Liu Y, Liu W, Sun G, Wei X, Yi D. Calcification resistance of procyanidin-treated decellularized porcine aortic valves in vivo. Heart Surg Forum. 2009 Jan;12(1):E24-9

Peng CC, Hsieh CL, Ker YB, Wang HY, Chen KC, Peng RY. Selected nutraceutic screening by therapeutic effects on doxorubicin-induced chronic kidney disease. Mol Nutr Food Res. 2012 Oct;56(10):1541-58

Nicoll R, Henein MY. Alcohol and the heart. Alcohol Clin Exp Res. 2011; 35(10); 1737-8

Vliegenthart R, Oei HH, van den Elzen AP et al. Alcohol consumption and coronary calcification in general population. Arch Intern Med. 2004; 164; 2355-660

McClelland RL, Bild DE, Burke GL, Mukamal KJ, Lima JA, Kronmal RA; Multi-Ethnic Study of Atherosclerosis. Alcohol and coronary artery calcium prevalence, incidence, and progression: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr. 2008 Dec;88(6):1593-601.

Tomayko EJ, Cachia AJ, Chung HR, Wilund KR. Resveratrol supplementation reduces aortic atherosclerosis and calcification and attenuates loss of aerobic capacity in a mouse model of uremia. J Med Food. 2014 Feb;17(2):278-83

Takemura A, Iijima K, Ota H, Son BK, Ito Y, Ogawa S, Eto M, Akishita M, Ouchi Y. Sirtuin 1 retards hyperphosphatemia-induced calcification of vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2011 Sep;31(9):2054-62

Mattison JA, Wang M, Bernier M, Zhang J, Park SS, Maudsley S 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

Negrao MR, Keating E, Faria A, Azevedo I, Martins MJ. ‘Acute effect of tea, wine, beer and polyphenols on ecto-alkaline phosphatase activity in human vascular smooth muscle cells’. J Agric Food Chem. 2006; 54(14): 4982-8

Johnell OJ, Gullberg B, Kanis JA et al. Risk factors for hip fracture in European women: the MEDOS study. J Bone Miner Res. 1995; 10: 1802-1815

Hegarty VM, May HM, Khaw KT. Tea drinking and bone mineral density in older women. Am J Clin Nutr. 2000; 71: 1003-1007

Muraki S, Yamamoto S, Ishibashi H, Horiuchi T, Hosoi T, Suzuki T et al. Green tea drinking is associated with increased bone mineral density. J Bone Miner Res. 2003; 18: Suppl 2: S241

Vestergaard P, Herman AP, Gram J et al. Evaluation of methods for prediction of bone mineral density by clinical and biochemical variables in perimenopausal women. Maturitas. 2001; 40: 211-220

Yano K,Heilbrun LK, Wasnich RD, Hankin JH, Vogel JM. The relationship between diet and bone mineral content of multiple skeletal sites in ealderly Japanese-American men and women living in Hawaii. Am J Clin Nutr. 1985; 42: 877-888

Kiel DP, Felson DT, Hannan MT, Anderson JJ, Wilson PW. Caffeine and the risk of hip fracture: the Framinghan Study. Am J Epidemiol. 1990; 132: 675-684

Dew TP, Day AJ, Morgan MRA. Bone mineral density, polyphenols and caffeine: a reassessment. Nutr Res Rev. 2007; 20: 89-105

Tucker K. Osteoporosis prevention and nutrition. Curr Osteopor Rep. 2009; 7: 111-117

Parazzini F. Resveratrol, inositol, vitamin D and K in the prevention of cardiovascular and osteoporotic risk: a novel approach in peri- and postmenopause. Minerva Ginecol. 2014 Oct;66(5):513-8

Kim HS, Shin HI, Lim HS, Lee TY, Lee K, Jeong D. ‘α-Lipoic acid attenuates coxsackievirus B3-induced ectopic calcification in heart, pancreas, and lung’. Biochem Biophys Res Commun. 2013 Mar 8;432(2):378-83

Bassi E, Liberman M, Martinatti MK, Bortolotto LA, Leurindo FR. Lipoic acid, but not tempol, preserves vascular compliance and decreases medial calcification in a model of elastocalcinosis. Braz J Med Biol Res. 2014; 47(2): 119-27

Mainini G, Rotondi M, Di Nola K, Pezzella MT, Iervolino SA, Seguino E, D'Eufemia D, Iannicelli I, Torella M. Oral supplementation with antioxidant agents containing alpha lipoic acid: effects on postmenopausal bone mass. Clin Exp Obstet Gynecol. 2012;39(4):489-93

Polat B, Halici Z, Cadirci E, Albayrak A, Karakus E, Bayir Y, Bilen H, Sahin A, Yuksel TN. The effect of alpha-lipoic acid in ovariectomy and inflammation-mediated osteoporosis on the skeletal status of rat bone. Eur J Pharmacol. 2013 Oct 15;718(1-3):469-74

Hah YS, Sung MJ, Lim HS, Jun JS, Jeong YG, Kim HO, Kim J, Hur HJ, Davaatseren M, Kwon DY, Lee SI. Dietary alpha lipoic acid supplementation prevents synovial inflammation and bone destruction in collagen-induced arthritic mice. Rheumatol Int. 2011 Dec;31(12):1583-90

Xiao Y, Cui J, Shi Y, Le G. Lipoic acid increases the expression of genes involved in bone formation in mice fed a high-fat diet. Nutr Res. 2011 Apr;31(4):309-17

Ivanovski O, Nikolov IG, Drueke BT, Massy AZ. ‘Atherosclerosis and vascular calcification in uraemia – a new experimental model’. Prilozi. 2007; 28(2): 11-24

Fujita H, Yamamoto M, Ogino T, Kobuchi H, Ohmoto N, Aoyama E et al. ‘Necrotic and apoptotic cells serve as nuclei for calcification on osteoblastic differentiation of human mesenchymal stem cells in vitro’. Cell Biochem Funct. 2014; 32(1): 77-86

Nakahara T, Sato H, Shimizu T, Tanaka T, Matsui H, Kawai-Kowase K, Sato M, Iso T, Arai M, Kurabayashi M. Fibroblast growth factor-2 induces osteogenic differentiation through a Runx2 activation in vascular smooth muscle cells. Biochem Biophys Res Commun. 2010 Apr 2;394(2):243-8

Shankar K, Hidestrand M, Liu X, Chen JR, Haley R, Perrien DS, Skinner RA, Lumpkin CK Jr, Badger TM, Ronis MJ. Chronic ethanol consumption inhibits postlactational anabolic bone rebuilding in female rats. J Bone Miner Res. 2008 Mar;23(3):338-49

Yamada M, Tsukimura N, Ikeda T, Sugita Y, Att W, Kojima N, Kubo K, Ueno T, Sakurai K, Ogawa T. N-acetyl cysteine as an osteogenesis-enhancing molecule for bone regeneration. Biomaterials. 2013 Aug;34(26):6147-56

Chae HJ, Chae SW, Kim HR. N-acetyl cysteine regulates TNF-alpha-inhibited differentiation in ROS 17/2.8 osteoblasts. Immunopharmacol Immunotoxicol. 2004 May;26(2):203-13

Koh JM, Lee YS, Kim YS, Kim DJ, Kim HH, Park JY, Lee KU, Kim GS. Homocysteine enhances bone resorption by stimulation of osteoclast formation and activity through increased intracellular ROS generation. J Bone Miner Res. 2006 Jul;21(7):1003-11

Fairus S, Nor RM, Cheng HM, Sundram K. Alpha-tocotrienol is the most abundant tocotrienol isomer circulated in plasma and lipoproteins after postprandial tocotrienol-rich vitamin E supplementation. Nutr J. 2012 Jan 17;11:5.

Uchida T, Nomura S, Ichikawa T, Abe C, Ikeda S. Tissue distribution of vitamin E metabolites in rats after oral administration of tocopherol or tocotrienol. J Nutr Sci Vitaminol (Tokyo). 2011;57(5):326-32.

Ikeda S, Tohyama T, Yoshimura H, Hamamura K, Abe K, Yamashita K. Dietary alpha-tocopherol decreases alpha-tocotrienol but not gamma-tocotrienol concentration in rats. J Nutr. 2003 Feb;133(2):428-34