Plausible ergogenic effects of vitamin D on athletic performance and recovery

Dylan T Dahlquist, Brad P Dieter, Michael S Koehle, Dylan T Dahlquist, Brad P Dieter, Michael S Koehle

Abstract

The purpose of this review is to examine vitamin D in the context of sport nutrition and its potential role in optimizing athletic performance. Vitamin D receptors (VDR) and vitamin D response elements (VDREs) are located in almost every tissue within the human body including skeletal muscle. The hormonally-active form of vitamin D, 1,25-dihydroxyvitamin D, has been shown to play critical roles in the human body and regulates over 900 gene variants. Based on the literature presented, it is plausible that vitamin D levels above the normal reference range (up to 100 nmol/L) might increase skeletal muscle function, decrease recovery time from training, increase both force and power production, and increase testosterone production, each of which could potentiate athletic performance. Therefore, maintaining higher levels of vitamin D could prove beneficial for athletic performance. Despite this situation, large portions of athletic populations are vitamin D deficient. Currently, the research is inconclusive with regards to the optimal intake of vitamin D, the specific forms of vitamin D one should ingest, and the distinct nutrient-nutrient interactions of vitamin D with vitamin K that affect arterial calcification and hypervitaminosis. Furthermore, it is possible that dosages exceeding the recommendations for vitamin D (i.e. dosages up to 4000-5000 IU/day), in combination with 50 to 1000 mcg/day of vitamin K1 and K2 could aid athletic performance. This review will investigate these topics, and specifically their relevance to athletic performance.

Keywords: Athlete; Dosage; Hormones; Performance; Recovery; Skeletal muscle; Testosterone; Vitamin D; Vitamin K.

Figures

Fig. 1
Fig. 1
Metabolism of vitamin D3 derived from the diet, pharmacological analogs and natural sunlight to the major circulating metabolite of vitamin D (25-hydroxyvitamin D), and subsequently to the active hormonal form, 1,25 dihydroxyvtiamin D
Fig. 2
Fig. 2
Dietary sources of vitamin D3 and D2 through whole (natural) or fortified food sources

References

    1. McCollum E, Simmonds N, Becker J, Shipley P. An experimental demonstration of the existence of a vitamin which promotes calcium deposition. J Biol Chem. 1922;1922:293–298.
    1. Jones G. Metabolism and biomarkers of vitamin D. Scand J Clin Lab Invest. 2012;72(Suppl 243):7–13.
    1. Wang T-T, Tavera-Mendoza LE, Laperriere D, Libby E, MacLeod NB, Nagai Y, et al. Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005;19:2685–95.
    1. Smith DT, Broughton KS, Larson-meyer DE. Vitamin D status and biomarkers of inflammation in runners. 2012;3:35–42.
    1. Alvarez-Díaz S, Valle N, García JM, Peña C, Freije JMP, Quesada V, et al. Cystatin D is a candidate tumor suppressor gene induced by vitamin D in human colon cancer cells. J Clin Invest. 2009;119:2343–58. doi: 10.1172/JCI37205.
    1. Dhesi JK, Jackson SHD, Bearne LM, Moniz C, Hurley MV, Swift CG, et al. Vitamin D supplementation improves neuromuscular function in older people who fall. Age Ageing. 2004;33:589–95. doi: 10.1093/ageing/afh209.
    1. Reddy Vanga S, Good M, Howard PA, Vacek JL. Role of vitamin D in cardiovascular health. Am J Cardiol. 2010;106:798–805. doi: 10.1016/j.amjcard.2010.04.042.
    1. Sukumar D, Shapses SA, Schneider SH. Vitamin D supplementation during short-term caloric restriction in healthy overweight/obese older women: effect on glycemic indices and serum osteocalcin levels. Mol Cell Endocrinol. 2015;410:1–5.
    1. Schoenmakers I, Francis RM, McColl E, Chadwick T, Goldberg GR, Harle C, et al. Vitamin D supplementation in older people (VDOP): Study protocol for a randomised controlled intervention trial with monthly oral dosing with 12,000 IU, 24,000 IU or 48,000 IU of vitamin D3. Trials. 2013;14:299. doi: 10.1186/1745-6215-14-299.
    1. Close GL, Leckey J, Patterson M, Bradley W, Owens DJ, Fraser WD, et al. The effects of vitamin D(3) supplementation on serum total 25[OH]D concentration and physical performance: a randomised dose–response study. Br J Sports Med. 2013;47:692–6. doi: 10.1136/bjsports-2012-091735.
    1. Bendik I, Friedel A, Roos FF, Weber P, Eggersdorfer M. Vitamin D: a critical and essential micronutrient for human health. Front Physiol. 2014;5:248. doi: 10.3389/fphys.2014.00248.
    1. Grudet C, Malm J, Westrin A, Brundin L. Suicidal patients are deficient in vitamin D, associated with a pro-inflammatory status in the blood. Psychoneuroendocrinology. 2014;50C:210–9. doi: 10.1016/j.psyneuen.2014.08.016.
    1. Polak MA, Houghton LA, Reeder AI, Harper MJ, Conner TS. Serum 25-hydroxyvitamin D concentrations and depressive symptoms among young adult men and women. Nutrients. 2014;6:4720–30. doi: 10.3390/nu6114720.
    1. Chei CL, Raman P, Yin Z-X, Shi X-M, Zeng Y, Matchar DB. Vitamin D levels and cognition in elderly adults in China. J Am Geriatr Soc. 2014;62(11):2125–9. doi: 10.1111/jgs.13082.
    1. Holick MF. Vitamin D: its role in cancer prevention and treatment. Prog Biophys Mol Biol. 2006;92:49–59. doi: 10.1016/j.pbiomolbio.2006.02.014.
    1. Guillot X, Prati C, Wendling D. Vitamin D and spondyloarthritis. Expert Rev Clin Immunol. 2014;10:1581–9. doi: 10.1586/1744666X.2014.972944.
    1. Welch TR, Bergstrom WH, Tsang RC. Vitamin D-deficient rickets: the reemergence of a once-conquered disease. J Pediatr. 2000;137:143–5. doi: 10.1067/mpd.2000.109008.
    1. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014;21:319–29. doi: 10.1016/j.chembiol.2013.12.016.
    1. Ogan D, Pritchett K. Vitamin D and the athlete: risks, recommendations, and benefits. Nutrients. 2013;5:1856–68. doi: 10.3390/nu5061856.
    1. Sato Y, Iwamoto J, Kanoko T, Satoh K. Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial. Cerebrovasc Dis. 2005;20:187–92. doi: 10.1159/000087203.
    1. Glerup H, Mikkelsen K, Poulsen L, Hass E, Overbeck S, Andersen H, et al. Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement. Calcif Tissue Int. 2000;66:419–24. doi: 10.1007/s002230010085.
    1. Pfeifer M, Begerow B, Minne H. Vitamin D and muscle function. Osteoporos Int. 2002;3:187–94. doi: 10.1007/s001980200012.
    1. Macdougall JD, Hicks AL, Macdonald JR, Mckelvie RS, Green HJ, Smith KM. Muscle performance and enzymatic adaptations to sprint interval training. J Appl Physiol. 1998;84:2138–142.
    1. Farrokhyar F, Tabasinejad R, Dao D, Peterson D, Ayeni O, Hadioonzadeh R, et al. Prevalence of vitamin D inadequacy in athletes: A systematic-review and meta-analysis. Sport Med. 2014;5:365–78.
    1. Calvo M, Whiting S. Prevalence of vitamin D insufficiency in Canada and the United States: importance to health status and efficacy of current food fortification and dietary supplement use. Nutr Rev. 2003;61:107–13. doi: 10.1301/nr.2003.marr.107-113.
    1. Hossein-nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013;88:720–55. doi: 10.1016/j.mayocp.2013.05.011.
    1. Schlögl M, Holick MF. Vitamin D and neurocognitive function. Clin Interv Aging. 2014;9:559–68.
    1. Holick MF. Vitamin D: evolutionary, physiological and health perspectives. Curr Drug Targets. 2011;12:4–18. doi: 10.2174/138945011793591635.
    1. Prosser DE, Jones G. Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem Sci. 2004;29:664–73. doi: 10.1016/j.tibs.2004.10.005.
    1. Bischoff H, Borchers M, Gudat F, Duermueller U, Theiler R, Stähelin H, et al. In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Histochem J. 2001;33:19–24.
    1. Simpson R, Thomas G, Arnold A. Identification of 1,25-dihydroxyvitamin D3 receptors and activities in muscle*. J Biol Chem. 1985;260:8882–891.
    1. Hamilton B. Vitamin d and athletic performance: the potential role of muscle. Asian J Sports Med. 2011;2:211–19.
    1. Stockton KA, Mengersen K, Paratz JD, Kandiah D, Bennell KL. Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis. Osteoporos Int. 2010;22:859–71.
    1. Tomlinson PB, Joseph C, Angioi M. Effects of vitamin D supplementation on upper and lower body muscle strength levels in healthy individuals. A systematic review with meta-analysis. J Sci Med Sport. 2014;18(5):575-80.
    1. Beaudart C, Buckinx F, Rabenda V, Gillain S, Cavalier E, Slomian J, et al. The effects of vitamin D on skeletal muscle strength, muscle mass and muscle power: A systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2014;99:4336–345.
    1. Von Hurst PR, Beck KL. Vitamin D and skeletal muscle function in athletes. Curr Opin Clin Nutr Metab Care. 2014;17:539–45. doi: 10.1097/MCO.0000000000000105.
    1. Gregory SM, Parker BA, Capizzi JA, Grimaldi AS, Clarkson PM, Moeckel-Cole S, et al. Changes in vitamin D are not associated with changes in cardiorespiratory fitness. Clin Med Res. 2013;2:68. doi: 10.11648/j.cmr.20130204.16.
    1. Mowry DA, Costello MM, Heelan KA. Association among cardiorespiratory fitness, body fat, and bone marker measurements in healthy young females. J Am Osteopath Assoc. 2009;109(10):534–9.
    1. Ardestani A, Parker B, Mathur S, Clarkson P, Pescatello LS, Hoffman HJ, et al. Relation of vitamin D level to maximal oxygen uptake in adults. Am J Cardiol. 2011;107:1246–9. doi: 10.1016/j.amjcard.2010.12.022.
    1. Koundourakis NE, Androulakis NE, Malliaraki N, Margioris AN. Relation of vitamin D level to maximal oxygen uptake in adults. Am J Cardiol. 2011;107:1246–9.
    1. Fitzgerald J, Peterson B, Warpeha J, Wilson P, Rhodes G, Ingraham S. Vitamin D status and VO2peak during a skate treadmill graded exercise test in competitive ice hockey players. J Strength Cond Res. 2014;28:3200–5. doi: 10.1519/JSC.0000000000000523.
    1. Forney L, Earnest CC, Henagan T, Johnson L, Castleberry T, Stewart L. Vitamin D Status, Body Composition, and Fitness Measures in College-Aged Students. J Strength Cond Res. 2014;28:814–24. doi: 10.1519/JSC.0b013e3182a35ed0.
    1. Jastrzębski Z. Effect of vitamin D supplementation on the level of physical fitness and blood parameters of rowers during the 8-week high intensity training. Facicula Educ Fiz şi Sport. 2014;2:57–67.
    1. Sugimoto H, Shiro Y. Diversity and substrate specificity in the structures of steroidogenic cytochrome P450 enzymes. Biol Pharm Bull. 2012;35:818–23. doi: 10.1248/bpb.35.818.
    1. D’Antona G, Lanfranconi F, Pellegrino MA, Brocca L, Adami R, Rossi R, et al. Skeletal muscle hypertrophy and structure and function of skeletal muscle fibres in male body builders. J Physiol. 2006;570(Pt 3):611–27. doi: 10.1113/jphysiol.2005.101642.
    1. Schoenfeld B. The mechanisms of muscle hypertrophy and their application to resistance training. J Strength Cond Res. 2010;24:2857–72. doi: 10.1519/JSC.0b013e3181e840f3.
    1. Schoenfeld B. Does exercise-induced muscle damage play a role in skeletal muscle hypertrophy? J Strength Cond Res. 2012;26:1441–53. doi: 10.1519/JSC.0b013e31824f207e.
    1. Garcia LA, Ferrini MG, Norris KC, Artaza JN. 1,25(OH)2vitamin D3 enhances myogenic differentiation by modulating the expression of key angiogenic growth factors and angiogenic inhibitors in C2C12 skeletal muscle cells. J Steroid Biochem Mol Biol. 2013;133:1–11. doi: 10.1016/j.jsbmb.2012.09.004.
    1. Garcia LA, King KK, Ferrini MG, Norris KC, Artaza JN. 1,25(OH)2vitamin D3 stimulates myogenic differentiation by inhibiting cell proliferation and modulating the expression of promyogenic growth factors and myostatin in C2C12 skeletal muscle cells. Endocrinology. 2011;152:2976–86. doi: 10.1210/en.2011-0159.
    1. Stratos I, Li Z, Herlyn P, Rotter R, Behrendt A-K, Mittlmeier T, et al. Vitamin D increases cellular turnover and functionally restores the skeletal muscle after crush injury in rats. Am J Pathol. 2013;182:895–904.
    1. Lund D, Cornelison D. Enter the matrix: shape, signal and superhighway. FEBS J. 2013;280:4089–99. doi: 10.1111/febs.12171.
    1. Barker T, Schneider ED, Dixon BM, Henriksen VT, Weaver LK. Supplemental vitamin D enhances the recovery in peak isometric force shortly after intense exercise. Nutr Metab (Lond) 2013;10:69. doi: 10.1186/1743-7075-10-69.
    1. Ainbinder A, Boncompagni S, Protasi F, Dirksen RT. Role of mitofusin-2 in mitochondrial localization and calcium uptake in skeletal muscle. Cell Calcium. 2015;57:14–24.
    1. Todd JJ, Pourshahidi KL, McSorley EM, Madigan SM, Magee PJ. Vitamin D: Recent advances and implications for athletes. Sport Med. 2015;45:213–29.
    1. Ceglia L, Niramitmahapanya S, da Silva MM, Rivas DA, Harris SS, Bischoff-Ferrari H, et al. A randomized study on the effect of vitamin D3 supplementation on skeletal muscle morphology and vitamin D receptor concentration in older women. J Clin Endocrinol Metab. 2013;98:E1927–35.
    1. Close GL, Russell J, Cobley JN, Owens DJ, Wilson G, Fraser WD, et al. Assessment of vitamin D concentration in non-supplemented professional athletes and healthy adults during the winter months in the UK: implications for skeletal muscle function. J Sports Sci. 2013;31:344–53.
    1. Mauras N, Hayes V, Welch S, Rini A, Helgeson K, Dokler M, Veldhuis JD, Urban RJ. Testosterone deficiency in young men: Marked alterations in whole body protein kinetics, strength, and adiposity*. J Clin Endocrinol Metab. 1998;83:1886–892.
    1. Wehr E, Pilz S, Boehm B, März W, Obermayer-Pietsch B. Association of vitamin D status with serum androgen levels in men. Clin Endocrinol (Oxf). 2010;73:243–8.
    1. Pilz S, Frisch S, Koertke H, Kuhn J, Dreier J, Obermayer-Pietsch B, et al. Effect of vitamin D supplementation on testosterone levels in men. Horm Metab Res. 2011;43:223–5.
    1. Kinuta K, Tanaka H, Moriwake T, Aya K, Kato S, Seino Y. Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads*. Endocrinology 200AD, 141:1317–324.
    1. Blomberg Jensen M, Nielsen JE, Jørgensen A, Rajpert-De Meyts E, Kristensen DM, Jørgensen N, et al. Vitamin D receptor and vitamin D metabolizing enzymes are expressed in the human male reproductive tract. Hum Reprod. 2010;25:1303–11.
    1. Blomberg Jensen M, Dissing S. Non-genomic effects of vitamin D in human spermatozoa. Steroids. 2012;77:903–9. doi: 10.1016/j.steroids.2012.02.020.
    1. Herbst KL, Bhasin S. Testosterone action on skeletal muscle. Curr Opin Clin Nutr Metab Care. 2004;7:271–7. doi: 10.1097/00075197-200405000-00006.
    1. Urban RJ. Growth hormone and testosterone: Anabolic effects on muscle. Horm Res Pædiatrics. 2011;76:81–3.
    1. Holick M, MacLaughlin J, Clark M, Holick S, Potts J, Anderson R, et al. Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Am Assoc Adv Sci. 1980;210:203–05.
    1. Webb AR. Who, what, where and when-influences on cutaneous vitamin D synthesis. Prog Biophys Mol Biol. 2006;92:17–25. doi: 10.1016/j.pbiomolbio.2006.02.004.
    1. Gilchrest B. Sun exposure and vitamin D sufficiency. Am J Clin Nutr. 2008;88:570–7.
    1. Lim HW, Gilchrest BA, Cooper KD, Bischoff-Ferrari HA, Rigel DS, Cyr WH, et al. Sunlight, tanning booths, and vitamin D. J Am Acad Dermatol. 2005;52:868–76.
    1. Wolpowitz D, Gilchrest BA. The vitamin D questions: how much do you need and how should you get it? J Am Acad Dermatol. 2006;54:301–17. doi: 10.1016/j.jaad.2005.11.1057.
    1. Holick MF. Sunligth "D"ilemma: Risk of skin cancer or bone disease and muscle weakness. Lancet 2001:4–6.
    1. Heaney RP. Vitamin D in health and disease. Clin J Am Soc Nephrol. 2008;3:1535–41. doi: 10.2215/CJN.01160308.
    1. Mithal A, Wahl DA, Bonjour J-P, Burckhardt P, Dawson-Hughes B, Eisman JA, et al. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int. 2009;20:1807–20.
    1. Walker N, Love TD, Baker DF, Healey PB, Haszard J, Edwards AS, et al. Knowledge and attitudes to vitamin D and sun exposure in elite New Zealand athletes: a cross-sectional study. J Int Soc Sports Nutr. 2014;11:47.
    1. Matsuoka LY, Wortsman J, Hollis BW. Use of topical sunscreen for the evaluation of regional synthesis of vitamin D3. J Am Acad Dermatol. 1990;22:772–5. doi: 10.1016/0190-9622(90)70107-S.
    1. Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr. 2012;95:1357–64.
    1. Holick M. Vitamin D deficiency. N Engl J Med. 2007;357:266–281. doi: 10.1056/NEJMra070553.
    1. Houghton L,A, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006;84:694–7.
    1. Logan VF, Gray AR, Peddie MC, Harper MJ, Houghton LA. Long-term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the winter months. Br J Nutr. 2013;109:1082–8. doi: 10.1017/S0007114512002851.
    1. Harris SS, Dawson-Hughes B. Plasma vitamin D and 25OHD responses of young and old men to supplementation with vitamin D3. J Am Coll Nutr. 2002;21:357–62. doi: 10.1080/07315724.2002.10719235.
    1. Post JL, Ilich Ernst JZ. Controversies in vitamin D recommendations and its possible roles in nonskeletal health issues. J Nutr Food Sci. 2013;03:1–5.
    1. Ross AC, Taylor CL. Yaktine AL. Calcium Vitamin D: Valle HB Del; 2011.
    1. Endocrine S. Evalutation, treatment, and prevention of vitamin D deficiency: An endocrine society clinical practice guideline. 2011.
    1. Vieth R. Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults. J Steroid Biochem Mol Biol. 2004;89–90:575–9. doi: 10.1016/j.jsbmb.2004.03.038.
    1. Cannell J, Hollis B. Use of vitamin D in clinical practice. Altern Med Rev. 2008;13:6–20.
    1. Heaney RP. Assessing vitamin D status. Curr Opin Clin Nutr Metab Care. 2011;14:440–44.
    1. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999;69:842–56.
    1. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006;84:18–28.
    1. Pramyothin P, Holick MF. Vitamin D supplementation: guidelines and evidence for subclinical deficiency. Curr Opin Gastroenterol. 2012;28:139–50. doi: 10.1097/MOG.0b013e32835004dc.
    1. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30.
    1. Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr. 2005;135:317–22.
    1. Engelman CD. Vitamin D recommendations: the saga continues. J Clin Endocrinol Metab. 2011;96:3065–6. doi: 10.1210/jc.2011-2355.
    1. Barger-Lux MJ, Heaney RP, Dowell S, Chen TC, Holick MF. International original article vitamin D and its major metabolites : Serum levels after graded oral dosing in healthy men. Osteoporos Int. 1998;25:222–30. doi: 10.1007/s001980050058.
    1. Lappe J, Cullen D, Haynatzki G, Recker R, Ahlf R, Thompson K. Calcium and vitamin d supplementation decreases incidence of stress fractures in female navy recruits. J Bone Miner Res. 2008;23:741–9. doi: 10.1359/jbmr.080102.
    1. Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16:713–6. doi: 10.1007/s00198-005-1867-7.
    1. Heaney RP, Davies KM, Chen TC, Holick MF, Janet Barger-Lux M. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77:204–10.
    1. Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab. 1988;67:373–8. doi: 10.1210/jcem-67-2-373.
    1. Valtueña J, Dominguez D, Til L, González-Gross M, Drobnic F. High prevalence of vitamin D insufficiency among elite Spanish athletes the importance of outdoor training adaptation. Nutr Hosp. 2014;30:124–31.
    1. Villacis D, Yi A, Jahn R, Kephart CJ, Charlton T, Gamradt SC, et al. Prevalence of Abnormal Vitamin D Levels Among Division I NCAA Athletes. Sports Health. 2014;6:340–7.
    1. Constantini NW, Arieli R, Chodick G, Dubnov-Raz G. High prevalence of vitamin D insufficiency in athletes and dancers. Clin J Sport Med. 2010;20:368–71. doi: 10.1097/JSM.0b013e3181f207f2.
    1. Holick MF. The vitamin D epidemic and its health consequences. J Nutr. 2005;135:2739S–48.
    1. Van den Ouweland J, Fleuren H, Drabbe M, Vollaard H. Pharmacokinetics and safety issues of an accidental overdose of 2,000,000 IU of vitamin D3 in two nursing home patients: a case report. BMC Pharmacol Toxicol. 2014;15:57. doi: 10.1186/2050-6511-15-57.
    1. Suda T, Ueno Y, Fujii K, Shinki T. Vitamin D and bone. J Cell Biochem. 2003;88:259–66S.
    1. Zittermann A. Vitamin D and cardiovascular disease. Anticancer Res. 2014;34:4641–648.
    1. Kidd PM. Vitamins D and K as pleiotropic nutrients: clinical importance to the skeletal and cardiovascular systems and preliminary evidence for synergy. Altern Med Rev. 2010;15:199–222.
    1. Gundberg CM, Lian JB, Booth SL. Vitamin K-dependent carboxylation of osteocalcin: friend or foe? Adv Nutr An. 2012;3:149–157. doi: 10.3945/an.112.001834.
    1. Mizuguchi M, Fujisawa R, Nara M, Nitta K, Kawano K. Fourier-Transform infrared spectroscopic study of Ca2 + −binding to osteocalcin. Calcif Tissue Int. 2001;69:337–42. doi: 10.1007/s002230010042.
    1. Fitzpatrick TB, Basset GJC, Borel P, Carrari F, DellaPenna D, Fraser PD, et al. Vitamin deficiencies in humans: can plant science help? Plant Cell. 2012;24:395–414.
    1. Binkley NC, Krueger DC, Kawahara TN, Engelke JA, Chappell RJ, Suttie JW. A high phylloquinone intake is required to achieve maximal osteocalcin γ-carboxylation. Am J Clin Nutr. 2002;76:1055–60.
    1. Akiyama Y, Hara K, Tajima T, Murota S, Morita I. Effect of vitamin K2 (menatetrenone) on osteoclast-like cell formation in mouse bone marrow cultures. Eur J Pharmacol. 1994;263:181–5. doi: 10.1016/0014-2999(94)90539-8.
    1. Akiyama Y, Hara K, Kobayashi M, Tomiuga T, Nakamura T. Inhibitory Effect of Vitamin K2 (Menatetrenone) on Bone Resorption in Ovariectomized Rats. A Histomorphometric and Dual Energy X-Ray Absorptiometic Study. The Japanese Journal of Pharmacology. 1999;80(1):67–74. doi: 10.1254/jjp.80.67.
    1. Feskanich D, Weber P, Willett WC, Rockett H, Booth SL, Colditz GA. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr. 1999;69:74–9.
    1. Masterjohn C. Vitamin D toxicity redefined: vitamin K and the molecular mechanism. Med Hypotheses. 2007;68:1026–34. doi: 10.1016/j.mehy.2006.09.051.
    1. El Asmar MS, Naoum JJ, Arbid EJ. Vitamin k dependent proteins and the role of vitamin k2 in the modulation of vascular calcification: a review. Oman Med J. 2014;29:172–7. doi: 10.5001/omj.2014.44.
    1. Hamidi MS, Cheung AM. Vitamin K and musculoskeletal health in postmenopausal women. Mol Nutr Food Res. 2014;58:1647–57. doi: 10.1002/mnfr.201300950.
    1. Iwamoto J. Vitamin K2 therapy for postmenopausal osteoporosis. Nutrients. 2014;6:1971–80. doi: 10.3390/nu6051971.
    1. Murakami K, Yamanaka N, Ohnishi K, Fukayama M, Yoshino M. Inhibition of angiotensin I converting enzyme by subtilisin NAT (nattokinase) in natto, a Japanese traditional fermented food. Food Funct. 2012;3:674–8. doi: 10.1039/c2fo10245e.
    1. Dowd P, Hershline R, Ham SW, Naganathan S. Mechanism of action of vitamin K. Nat Prod Rep. 1994;11:251–64. doi: 10.1039/np9941100251.
    1. Fusaro M, Crepaldi G, Maggi S, Galli F, D’Angelo A, Calò L, et al. Vitamin K, bone fractures, and vascular calcifications in chronic kidney disease: an important but poorly studied relationship. J Endocrinol Invest. 2011;34:317–23.
    1. Konakion® . Konakion®. 2010. pp. 1–6.
    1. Craciun AM, Wolf J, Knapen MH, Brouns F, Vermeer C. Improved bone metabolism in female elite athletes after vitamin K supplementation. Int J Sports Med. 1998;19:479–84. doi: 10.1055/s-2007-971948.
    1. Visser M, Deeg DJ, Puts MT, Seidell JC, Lips P. Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admission. Am J Clin Nutr. 2006;84:671–672.

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