The Impact of Obesity on the Association between Vitamin D Deficiency and Cardiovascular Disease

Stavroula A Paschou, Marinos Kosmopoulos, Ilias P Nikas, Michael Spartalis, Evanthia Kassi, Dimitrios G Goulis, Irene Lambrinoudaki, Gerasimos Siasos, Stavroula A Paschou, Marinos Kosmopoulos, Ilias P Nikas, Michael Spartalis, Evanthia Kassi, Dimitrios G Goulis, Irene Lambrinoudaki, Gerasimos Siasos

Abstract

The aim of this article is to review the literature regarding the relationship between vitamin D deficiency and cardiovascular disease (CVD) and its modification in the presence of obesity. Despite the strong association between vitamin D status and cardiovascular outcomes, vitamin D supplementation trials in the general population have failed to decrease the incidence of cardiovascular events and mortality. A comprehensive study of the published literature and a comparison with experimental data lead to the conclusion that obesity, due to its high prevalence and strong association with both vitamin D deficiency and CVD, may act as a critical confounder, which is responsible for the different results on this association. Adoption of a vitamin D preventive supplementation strategy for CVD is unlikely to yield any benefit to the general population. However, it might be particularly useful in obese adults with increased risk for CVD.

Keywords: atherosclerosis; cardiovascular disease; obesity; vitamin D.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Proposed effects of vitamin D on obesity-related atherosclerotic progression. Vitamin D prevents further macrophage recruitment in atherosclerotic lesions and decreases vascular inflammation through inhibition of nuclear factor kappa B and decoying of reactive oxygen species. Obesity alleviates the beneficial effects of vitamin D on the vasculature by decreasing vitamin D bioavailability and augmenting the production of reactive oxygen species.

References

    1. Cano A., Chedraui P., Goulis D.G., Lopes P., Mishra G., Mueck A., Senturk L.M., Simoncini T., Stevenson J.C., Stute P., et al. Calcium in the prevention of postmenopausal osteoporosis: EMAS clinical guide. Maturitas. 2018;107:7–12. doi: 10.1016/j.maturitas.2017.10.004.
    1. Apostolakis M., Armeni E., Bakas P., Lambrinoudaki I. Vitamin D and cardiovascular disease. Maturitas. 2018;115:1–22. doi: 10.1016/j.maturitas.2018.05.010.
    1. Anagnostis P., Paschou S.A., Goulis D.G. Vitamin D Supplementation and Cardiovascular Disease Risk. JAMA Cardiol. 2017;2:1281–1282. doi: 10.1001/jamacardio.2017.2938.
    1. Andersen S.W., Shu X.O., Cai Q., Khankari N.K., Steinwandel M.D., Jurutka P.W., Blot W.J., Zheng W. Total and Free Circulating Vitamin D and Vitamin D-Binding Protein in Relation to Colorectal Cancer Risk in a Prospective Study of African Americans. Cancer Epidemiol Biomarkers Prev. 2017;26:1242–1247. doi: 10.1158/1055-9965.EPI-17-0133.
    1. Miclea A., Miclea M., Pistor M., Hoepner A., Chan A., Hoepner R. Vitamin D supplementation differentially affects seasonal multiple sclerosis disease activity. Brain Behav. 2017;7:e00761. doi: 10.1002/brb3.761.
    1. Lambrinoudaki I., Patikas E., Kaparos G., Armeni E., Rizos D., Thoda P., Alexandrou A., Antoniou A., Tsivgoulis G., Gatzonis S., et al. Vitamin D receptor Bsm1 polymorphism, calcium metabolism and bone mineral density in patients with multiple sclerosis: A pilot study. Neurol. Sci. 2013;34:1433–1439. doi: 10.1007/s10072-012-1259-7.
    1. Ross A.C., Manson J.E., Abrams S.A., Aloia J.F., Brannon P.M., Clinton S.K., Durazo-Arvizu R.A., Gallagher J.C., Gallo R.L., Jones G., et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: What clinicians need to know. J. Clin. Endocrinol. Metab. 2011;96:53–58. doi: 10.1210/jc.2010-2704.
    1. Heaney R.P., Holick M.F. Why the IOM recommendations for vitamin D are deficient. J. Bone Min. Res. 2011;26:455–457. doi: 10.1002/jbmr.328.
    1. Cashman K.D., Ritz C., Kiely M., Collaborators O. Improved Dietary Guidelines for Vitamin D: Application of Individual Participant Data (IPD)-Level Meta-Regression Analyses. Nutrients. 2017;9:469. doi: 10.3390/nu9050469.
    1. Roth D.E., Abrams S.A., Aloia J., Bergeron G., Bourassa M.W., Brown K.H., Calvo M.S., Cashman K.D., Combs G., De-Regil L.M., et al. Global prevalence and disease burden of vitamin D deficiency: A roadmap for action in low- and middle-income countries. Ann. N. Y. Acad. Sci. 2018;1430:44–79. doi: 10.1111/nyas.13968.
    1. Pilz S., Dobnig H., Tomaschitz A., Kienreich K., Meinitzer A., Friedl C., Wagner D., Piswanger-Sölkner C., März W., Fahrleitner-Pammer A. Low 25-hydroxyvitamin D is associated with increased mortality in female nursing home residents. J. Clin. Endocrinol. Metab. 2012;97:E653–E657. doi: 10.1210/jc.2011-3043.
    1. Karras S., Paschou S.A., Kandaraki E., Anagnostis P., Annweiler C., Tarlatzis B.C., Hollis B.W., Grant W.B., Goulis D.G. Hypovitaminosis D in pregnancy in the Mediterranean region: A systematic review. Eur. J. Clin. Nutr. 2016;70:979–986. doi: 10.1038/ejcn.2016.12.
    1. Afshin A., Forouzanfar M.H., Reitsma M.B., Sur P., Estep K., Lee A., Marczak L., Mokdad A.H., Moradi-Lakeh M., Naghavi M., et al. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N. Engl. J. Med. 2017;377:13–27.
    1. Roth G.A., Johnson C., Abajobir A., Abd-Allah F., Abera S.F., Abyu G., Ahmed M., Aksut B., Alam T., Alam K., et al. Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. J. Am. Coll. Cardiol. 2017;70:1–25. doi: 10.1016/j.jacc.2017.04.052.
    1. Piepoli M.F., Hoes A.W., Agewall S., Albus C., Brotons C., Catapano A.L., Cooney M.T., Corra U., Cosyns B., Deaton C., et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur. Heart J. 2016;37:2315–2381. doi: 10.1093/eurheartj/ehw106.
    1. Mason H., Shoaibi A., Ghandour R., O’Flaherty M., Capewell S., Khatib R., Jabr S., Unal B., Sözmen K., Arfa C., et al. A cost effectiveness analysis of salt reduction policies to reduce coronary heart disease in four Eastern Mediterranean countries. PLoS ONE. 2014;9:e84445. doi: 10.1371/journal.pone.0084445.
    1. O’Keeffe C., Kabir Z., O’Flaherty M., Walton J., Capewell S., Perry I.J. Modelling the impact of specific food policy options on coronary heart disease and stroke deaths in Ireland. BMJ Open. 2013;3:e002837. doi: 10.1136/bmjopen-2013-002837.
    1. Siasos G., Tousoulis D., Oikonomou E., Maniatis K., Kioufis S., Kokkou E., Vavuranakis M., Zaromitidou M., Kassi E., Miliou A., et al. Vitamin D3, D2 and arterial wall properties in coronary artery disease. Curr. Pharm. Des. 2014;20:5914–5918. doi: 10.2174/1381612820666140619122937.
    1. Giovannucci E., Liu Y., Hollis B.W., Rimm E.B. 25-hydroxyvitamin D and risk of myocardial infarction in men: A prospective study. Arch. Intern. Med. 2008;168:1174–1180. doi: 10.1001/archinte.168.11.1174.
    1. Welles C.C., Whooley M.A., Karumanchi S.A., Hod T., Thadhani R., Berg A.H., Ix J.H., Mukamal K.J. Vitamin D deficiency and cardiovascular events in patients with coronary heart disease: Data from the Heart and Soul Study. Am. J. Epidemiol. 2014;179:1279–1287. doi: 10.1093/aje/kwu059.
    1. Zhang R., Li B., Gao X., Tian R., Pan Y., Jiang Y., Gu H., Wang Y., Wang Y., Liu G. Serum 25-hydroxyvitamin D and the risk of cardiovascular disease: Dose-response meta-analysis of prospective studies. Am. J. Clin. Nutr. 2017;105:810–819. doi: 10.3945/ajcn.116.140392.
    1. Schöttker B., Jorde R., Peasey A., Thorand B., Jansen E.H., de Groot L., Streppel M., Gardiner J., Ordóñez-Mena J.M., Perna L., et al. Vitamin D and mortality: Meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ. 2014;348:g3656. doi: 10.1136/bmj.g3656.
    1. Faridi K.F., Zhao D., Martin S.S., Lupton J.R., Jones S.R., Guallar E., Ballantyne C.M., Lutsey P.L., Michos E.D. Serum vitamin D and change in lipid levels over 5 y: The Atherosclerosis Risk in Communities study. Nutrition. 2017;38:85–93. doi: 10.1016/j.nut.2017.01.008.
    1. Yin K., You Y., Swier V., Tang L., Radwan M.M., Pandya A.N., Agrawal D.K. Vitamin D Protects Against Atherosclerosis via Regulation of Cholesterol Efflux and Macrophage Polarization in Hypercholesterolemic Swine. Arterioscler. Thromb. Vasc. Biol. 2015;35:2432–2442. doi: 10.1161/ATVBAHA.115.306132.
    1. Chen S., Swier V.J., Boosani C.S., Radwan M.M., Agrawal D.K. Vitamin D Deficiency Accelerates Coronary Artery Disease Progression in Swine. Arterioscler. Thromb. Vasc. Biol. 2016;36:1651–1659. doi: 10.1161/ATVBAHA.116.307586.
    1. Antonopoulos A.S., Sanna F., Sabharwal N., Thomas S., Oikonomou E.K., Herdman L., Margaritis M., Shirodaria C., Kampoli A.M., Akoumianakis I., et al. Detecting human coronary inflammation by imaging perivascular fat. Sci. Transl. Med. 2017;9:eaal2658. doi: 10.1126/scitranslmed.aal2658.
    1. Hadjadj L., Monori-Kiss A., Horváth E.M., Heinzlmann A., Magyar A., Sziva R.E., Miklós Z., Pál É., Gál J., Szabó I., et al. Geometric, elastic and contractile-relaxation changes in coronary arterioles induced by Vitamin D deficiency in normal and hyperandrogenic female rats. Microvasc. Res. 2019;122:78–84. doi: 10.1016/j.mvr.2018.11.011.
    1. Ellam T., Hameed A., ul Haque R., Muthana M., Wilkie M., Francis S.E., Chico T.J. Vitamin D deficiency and exogenous vitamin D excess similarly increase diffuse atherosclerotic calcification in apolipoprotein E knockout mice. PLoS ONE. 2014;9:e88767. doi: 10.1371/journal.pone.0088767.
    1. Sunbul M., Bozbay M., Mammadov C., Cincin A., Atas H., Ozsenel E.B., Sari I., Basaran Y. Effect of vitamin D deficiency and supplementation on myocardial deformation parameters and epicardial fat thickness in patients free of cardiovascular risk. Int. J. Cardiovasc. Imaging. 2015;31:765–772. doi: 10.1007/s10554-015-0622-1.
    1. Farhangi M.A., Nameni G., Hajiluian G., Mesgari-Abbasi M. Cardiac tissue oxidative stress and inflammation after vitamin D administrations in high fat- diet induced obese rats. BMC Cardiovasc. Disord. 2017;17:161. doi: 10.1186/s12872-017-0597-z.
    1. Salum E., Kals J., Kampus P., Salum T., Zilmer K., Aunapuu M., Arend A., Eha J., Zilmer M. Vitamin D reduces deposition of advanced glycation end-products in the aortic wall and systemic oxidative stress in diabetic rats. Diabetes Res. Clin. Pract. 2013;100:243–249. doi: 10.1016/j.diabres.2013.03.008.
    1. Holick M.F. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am. J. Clin. Nutr. 2004;80:1678S–1688S. doi: 10.1093/ajcn/80.6.1678S.
    1. Al Mheid I., Quyyumi A.A. Vitamin D and Cardiovascular Disease: Controversy Unresolved. J. Am. Coll. Cardiol. 2017;70:89–100. doi: 10.1016/j.jacc.2017.05.031.
    1. Hsia J., Heiss G., Ren H., Allison M., Dolan N.C., Greenland P., Heckbert S.R., Johnson K.C., Manson J.E., Sidney S., et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007;115:846–854. doi: 10.1161/CIRCULATIONAHA.106.673491.
    1. Cauley J.A., Chlebowski R.T., Wactawski-Wende J., Robbins J.A., Rodabough R.J., Chen Z., Johnson K.C., O’Sullivan M.J., Jackson R.D., Manson J.E. Calcium plus vitamin D supplementation and health outcomes five years after active intervention ended: The Women’s Health Initiative. J. Women’s Health. 2013;22:915–929. doi: 10.1089/jwh.2013.4270.
    1. Scragg R., Stewart A.W., Waayer D., Lawes C.M., Toop L., Sluyter J., Murphy J., Khaw K.T., Camargo C.A. Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study: A Randomized Clinical Trial. JAMA Cardiol. 2017;2:608–616. doi: 10.1001/jamacardio.2017.0175.
    1. Manson J.E., Cook N.R., Lee I.M., Christen W., Bassuk S.S., Mora S., Gibson H., Gordon D., Copeland T., D’Agostino D., et al. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N. Engl. J. Med. 2019;380:33–44. doi: 10.1056/NEJMoa1809944.
    1. Forouhi N.G., Menon R.K., Sharp S.J., Mannan N., Timms P.M., Martineau A.R., Rickard A.P., Boucher B.J., Chowdhury T.A., Griffiths C.J., et al. Effects of vitamin D2 or D3 supplementation on glycaemic control and cardiometabolic risk among people at risk of type 2 diabetes: Results of a randomized double-blind placebo-controlled trial. Diabetes Obes. Metab. 2016;18:392–400. doi: 10.1111/dom.12625.
    1. Pilz S., Gaksch M., Kienreich K., Grübler M., Verheyen N., Fahrleitner-Pammer A., Treiber G., Drechsler C., ó Hartaigh B., Obermayer-Pietsch B., et al. Effects of vitamin D on blood pressure and cardiovascular risk factors: A randomized controlled trial. Hypertension. 2015;65:1195–1201. doi: 10.1161/HYPERTENSIONAHA.115.05319.
    1. Schnatz P.F., Jiang X., Aragaki A.K., Nudy M., O’Sullivan D.M., Williams M., LeBlanc E.S., Martin L.W., Manson J.E., Shikany J.M., et al. Effects of Calcium, Vitamin D, and Hormone Therapy on Cardiovascular Disease Risk Factors in the Women’s Health Initiative: A Randomized Controlled Trial. Obstet. Gynecol. 2017;129:121–129. doi: 10.1097/AOG.0000000000001774.
    1. Zittermann A., Ernst J.B., Prokop S., Fuchs U., Dreier J., Kuhn J., Knabbe C., Birschmann I., Schulz U., Berthold H.K., et al. Effect of vitamin D on all-cause mortality in heart failure (EVITA): A 3-year randomized clinical trial with 4000 IU vitamin D daily. Eur. Heart J. 2017;38:2279–2286. doi: 10.1093/eurheartj/ehx235.
    1. Makariou S.E., Elisaf M., Challa A., Tentolouris N., Liberopoulos E.N. No effect of vitamin D supplementation on cardiovascular risk factors in subjects with metabolic syndrome: A pilot randomised study. Arch. Med. Sci. Atheroscler. Dis. 2017;2:e52–e60. doi: 10.5114/amsad.2017.70504.
    1. Jepsen P., Johnsen S.P., Gillman M.W., Sorensen H.T. Interpretation of observational studies. Heart. 2004;90:956–960. doi: 10.1136/hrt.2003.017269.
    1. Plesner J.L., Dahl M., Fonvig C.E., Nielsen T.R.H., Kloppenborg J.T., Pedersen O., Hansen T., Holm J.C. Obesity is associated with vitamin D deficiency in Danish children and adolescents. J. Pediatr. Endocrinol. Metab. 2018;31:53–61. doi: 10.1515/jpem-2017-0246.
    1. Dylag H., Rowicka G., Strucinska M., Riahi A. Assessment of vitamin D status in children aged 1-5 with simple obesity. Rocz. Panstw. Zakl. Hig. 2014;65:325–330.
    1. Rontoyanni V.G., Avila J.C., Kaul S., Wong R., Veeranki S.P. Association between Obesity and Serum 25(OH)D Concentrations in Older Mexican Adults. Nutrients. 2017;9:97. doi: 10.3390/nu9020097.
    1. Forrest K.Y.Z., Stuhldreher W.L. Prevalence and correlates of vitamin D deficiency in US adults. Nutr. Res. 2011;31:48–54. doi: 10.1016/j.nutres.2010.12.001.
    1. Bettencourt A., Boleixa D., Reis J., Oliveira J.C., Mendonça D., Costa P.P., da Silva B.M., Marinho A., da Silva A.M. Serum 25-hydroxyvitamin D levels in a healthy population from the North of Portugal. J. Steroid Biochem. Mol. Biol. 2018;175:97–101. doi: 10.1016/j.jsbmb.2016.11.005.
    1. Stokić E., Kupusinac A., Tomić-Naglić D., Zavišić B.K., Mitrović M., Smiljenić D., Soskić S., Isenović E. Obesity and vitamin D deficiency: Trends to promote a more proatherogenic cardiometabolic risk profile. Angiology. 2015;66:237–243. doi: 10.1177/0003319714528569.
    1. Fatima S.S., Farooq S., Tauni M.A., Irfan O., Alam F. Effect of raised body fat on vitamin D, leptin and bone mass. J. Pak. Med. Assoc. 2015;65:1315–1319.
    1. Shafinaz I.S., Moy F.M. Vitamin D level and its association with adiposity among multi-ethnic adults in Kuala Lumpur, Malaysia: A cross sectional study. BMC Public Health. 2016;16:232. doi: 10.1186/s12889-016-2924-1.
    1. Calle E.E., Thun M.J., Petrelli J.M., Rodriguez C., Heath C.W.J. Body-mass index and mortality in a prospective cohort of U.S. adults. N. Engl. J. Med. 1999;341:1097–1105. doi: 10.1056/NEJM199910073411501.
    1. Caleyachetty R., Thomas G.N., Toulis K.A., Mohammed N., Gokhale K.M., Balachandran K., Nirantharakumar K. Metabolically Healthy Obese and Incident Cardiovascular Disease Events Among 3.5 Million Men and Women. J. Am. Coll. Cardiol. 2017;70:1429–1437. doi: 10.1016/j.jacc.2017.07.763.
    1. Berrington de Gonzalez A., Hartge P., Cerhan J.R., Flint A.J., Hannan L., MacInnis R.J., Moore S.C., Tobias G.S., Anton-Culver H., Freeman L.B., et al. Body-mass index and mortality among 1.46 million white adults. N. Engl. J. Med. 2010;363:2211–2219. doi: 10.1056/NEJMoa1000367.
    1. Sandfort V., Lai S., Ahlman M.A., Mallek M., Liu S., Sibley C.T., Turkbey E.B., Lima J.A., Bluemke D.A. Obesity Is Associated with Progression of Atherosclerosis During Statin Treatment. J. Am. Heart Assoc. 2016;5:e003621. doi: 10.1161/JAHA.116.003621.
    1. Ahmad F.S., Ning H., Rich J.D., Yancy C.W., Lloyd-Jones D.M., Wilkins J.T. Hypertension, Obesity, Diabetes, and Heart Failure-Free Survival: The Cardiovascular Disease Lifetime Risk Pooling Project. JACC Heart Fail. 2016;4:911–919. doi: 10.1016/j.jchf.2016.08.001.
    1. Kouli G.M., Panagiotakos D.B., Kyrou I., Georgousopoulou E.N., Chrysohoou C., Tsigos C., Tousoulis D., Pitsavos C. Visceral adiposity index and 10-year cardiovascular disease incidence: The ATTICA study. Nutr. Metab. Cardiovasc. Dis. 2017;27:881–889. doi: 10.1016/j.numecd.2017.06.015.
    1. Araujo J., Severo M., Barros H., Ramos E. Duration and degree of adiposity: Effect on cardiovascular risk factors at early adulthood. Int. J. Obes. 2017;41:1526–1530. doi: 10.1038/ijo.2017.133.
    1. Kelly A.S., Jacobs D.R.J., Sinaiko A.R., Moran A., Steffen L.M., Steinberger J. Relation of circulating oxidized LDL to obesity and insulin resistance in children. Pediatr. Diabetes. 2010;11:552–555. doi: 10.1111/j.1399-5448.2009.00640.x.
    1. Geiss L.S., Kirtland K., Lin J., Shrestha S., Thompson T., Albright A., Gregg E.W. Changes in diagnosed diabetes, obesity, and physical inactivity prevalence in US counties, 2004–2012. PLoS ONE. 2017;12:e0173428. doi: 10.1371/journal.pone.0173428.
    1. Wortsman J., Matsuoka L.Y., Chen T.C., Lu Z., Holick M.F. Decreased bioavailability of vitamin D in obesity. Am. J. Clin. Nutr. 2000;72:690–693. doi: 10.1093/ajcn/72.3.690.
    1. Mawer E.B., Backhouse J., Holman C.A., Lumb G.A., Stanbury S.W. The distribution and storage of vitamin D and its metabolites in human tissues. Clin. Sci. 1972;43:413–431. doi: 10.1042/cs0430413.
    1. Forbes G.B., Welle S.L. Lean body mass in obesity. Int. J. Obes. 1983;7:99–107.
    1. Cipriani C., Pepe J., Piemonte S., Colangelo L., Cilli M., Minisola S. Vitamin d and its relationship with obesity and muscle. Int. J. Endocrinol. 2014;2014:841248. doi: 10.1155/2014/841248.
    1. Jung Y.S., Wu D., Smith D., Meydani S.N., Han S.N. Dysregulated 1,25-dihydroxyvitamin D levels in high-fat diet-induced obesity can be restored by changing to a lower-fat diet in mice. Nutr. Res. 2018;53:51–60. doi: 10.1016/j.nutres.2018.03.008.
    1. Bonnet L., Hachemi M.A., Karkeni E., Couturier C., Astier J., Defoort C., Svilar L., Martin J.C., Tourniaire F., Landrier J.F. Diet induced obesity modifies vitamin D metabolism and adipose tissue storage in mice. J. Steroid Biochem. Mol. Biol. 2019;185:39–46. doi: 10.1016/j.jsbmb.2018.07.006.
    1. Wang Y., Buckendahl P., Sharma K., Miller J.W., Shapses S.A. Expression of vitamin D hydroxylases and bone quality in obese mice consuming saturated or monounsaturated enriched high-fat diets. Nutr. Res. 2018;60:106–115. doi: 10.1016/j.nutres.2018.08.006.
    1. Osmancevic A., Gillstedt M., Landin-Wilhelmsen K., Larkö A.M.W., Larkö O., Holick M.F., Krogstad A.L. Size of the exposed body surface area, skin erythema and body mass index predict skin production of vitamin D. J. Photochem. Photobiol. B. 2015;149:224–229. doi: 10.1016/j.jphotobiol.2015.06.008.
    1. Florez H., Martinez R., Chacra W., Strickman-Stein N., Levis S. Outdoor exercise reduces the risk of hypovitaminosis D in the obese. J. Steroid Biochem. Mol. Biol. 2007;103:679–681. doi: 10.1016/j.jsbmb.2006.12.032.
    1. Targher G., Bertolini L., Scala L., Cigolini M., Zenari L., Falezza G., Arcaro G. Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease. Nutr. Metab. Cardiovasc. Dis. 2007;17:517–524. doi: 10.1016/j.numecd.2006.04.002.
    1. Liu S., Liu Y., Wan B., Zhang H., Wu S., Zhu Z., Lin Y., Wang M., Zhang N., Lin S., et al. Association between Vitamin D Status and Non-Alcoholic Fatty Liver Disease: A Population-Based Study. J. Nutr. Sci. Vitam. 2019;65:303–308. doi: 10.3177/jnsv.65.303.
    1. Chang E., Kim Y. Vitamin D Insufficiency Exacerbates Adipose Tissue Macrophage Infiltration and Decreases AMPK/SIRT1 Activity in Obese Rats. Nutrients. 2017;9:338. doi: 10.3390/nu9040338.
    1. Shamardl H.A., El-Ashmony S.M., Kamel H.F., Fatani S.H. Potential Cardiovascular and Renal Protective Effects of Vitamin D and Coenzyme Q10 in l-NAME-Induced Hypertensive Rats. Am. J. Med. Sci. 2017;354:190–198. doi: 10.1016/j.amjms.2017.04.007.
    1. Andersen L.B., Przybyl L., Haase N., von Versen-Höynck F., Qadri F., Jørgensen J.S., Sorensen G.L., Fruekilde P., Poglitsch M., Szijarto I., et al. Vitamin D depletion aggravates hypertension and target-organ damage. J. Am. Heart Assoc. 2015;4:e001417. doi: 10.1161/JAHA.114.001417.
    1. Gupta G.K., Agrawal T., Rai V., Del Core M.G., Hunter W.J., 3rd, Agrawal D.K. Vitamin D Supplementation Reduces Intimal Hyperplasia and Restenosis following Coronary Intervention in Atherosclerotic Swine. PLoS ONE. 2016;11:e0156857. doi: 10.1371/journal.pone.0156857.
    1. Martins D., Meng Y.X., Tareen N., Artaza J., Lee J.E., Farodolu C., Gibbons G., Norris K. The Effect of Short Term Vitamin D Supplementation on the Inflammatory and Oxidative Mediators of Arterial Stiffness. Health. 2014;6:1503–1511. doi: 10.4236/health.2014.612185.
    1. Vimaleswaran K.S., Berry D.J., Lu C., Tikkanen E., Pilz S., Hiraki L.T., Cooper J.D., Dastani Z., Li R., Houston D.K., et al. Causal relationship between obesity and vitamin D status: Bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med. 2013;10:e1001383. doi: 10.1371/journal.pmed.1001383.
    1. Codoner-Franch P., Tavarez-Alonso S., Simo-Jorda R., Laporta-Martin P., Carratala-Calvo A., Alonso-Iglesias E. Vitamin D status is linked to biomarkers of oxidative stress, inflammation, and endothelial activation in obese children. J. Pediatr. 2012;161:848–854. doi: 10.1016/j.jpeds.2012.04.046.
    1. Gradinaru D., Borsa C., Ionescu C., Margina D., Prada G.I., Jansen E. Vitamin D status and oxidative stress markers in the elderly with impaired fasting glucose and type 2 diabetes mellitus. Aging Clin. Exp. Res. 2012;24:595–602.
    1. Wang E.W., Siu P.M., Pang M.Y., Woo J., Collins A.R., Benzie I.F.F. Vitamin D deficiency, oxidative stress and antioxidant status: Only weak association seen in the absence of advanced age, obesity or pre-existing disease. Br. J. Nutr. 2017;118:11–16. doi: 10.1017/S000711451700188X.

Source: PubMed

3
Abonnere