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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Review Article

Effect of Vitamin K Supplementation on Cardiometabolic Risk Factors: A Systematic Review and Meta-Analysis

Author(s): Hitesh Verma* and Rajeev Garg

Volume 19, Issue 1, 2019

Page: [13 - 25] Pages: 13

DOI: 10.2174/1871530318666180703125007

Price: $65

Abstract

Background: Multiple cross sectional and longitudinal studies reported the benefits of vitamin K intake for management of cardiometabolic risk factors so as to minimize the risk of cardiovascular diseases.

Objective: In present systematic review and meta-analysis, we aimed to evaluate the effect of vitamin K supplementation on cardiometabolic risk factors.

Methodology: A systematic literature search of PubMed, Cochrane central, Clinicaltrials.gov, Google Scholar, Web of Science, EBSCO and Scopus databases was done from inception to November, 2017. A total of 13 trials were selected for inclusion into the present systematic review to evaluate the effect of vitamin K supplementation on cardiometabolic risk factors in healthy or in population at high risk of cardiovascular diseases.

Results: Significant beneficial effects of vitamin K supplementation were found only in case of Creactive protein (p = 0.01) and insulin sensitivity index (p <0.001), while no significant effects of vitamin K supplementation were found in case of total cholesterol (p=0.857), low density lipoprotein – cholesterol (p=0.964), high density lipoprotein – cholesterol (p=0.998), interleukin – 6 (p=0.766), systolic blood pressure (p=0.660), diastolic blood pressure (p=0.818), fasting plasma glucose (p=0.362), fasting plasma insulin (p=0.928) and homeostasis model assessment for insulin resistance (p=0.672).

Conclusion: Presently available evidence are insufficient to ascertain the beneficial effects of vitamin K supplementation for the management of cardiometabolic risk factors. In order to explore the true potential of vitamin K supplementation for management of cardiometabolic diseases, large randomized placebo controlled trials are required in population with disturbed cardiometabolic profile. Present systematic review and meta-analysis is registered with PROSPERO (Registration number: CRD42018084608).

Keywords: Vitamin K, menaquinones, phylloquinone, cardiometabolic risk factors, supplementation, high density lipoprotein – cholesterol.

Graphical Abstract
[1]
Hansen, B.C. The metabolic syndrome X. Ann. N. Y. Acad. Sci., 1999, 18, 1-24.
[2]
Alberti, K.G.; Eckel, R.H.; Grundy, S.M.; Zimmet, P.Z.; Cleeman, J.I.; Donato, K.A.; Fruchart, J.C.; James, W.P.; Loria, C.M.; Smith, S.C., Jr International diabetes federation task force on epidemiology and prevention; National heart, lung, and blood institute; American heart association; World heart federation; International atherosclerosis society; International association for the study of obesity. Harmonizing the metabolic syndrome: A joint interim statement of the international diabetes federation task force on epidemiology and prevention; National heart, lung, and blood institute; American heart association; World heart federation; International atherosclerosis society; And international association for the study of obesity. Circulation, 2009, 120, 1640-1645.
[3]
Athyros, V.G.; Ganotakis, E.S.; Elisaf, M.; Mikhailidis, D.P. The prevalence of the metabolic syndrome using the national cholesterol educational program and international diabetes federation definitions. Curr. Med. Res. Opin., 2005, 21, 1157-1159.
[4]
Cameron, A.J.; Shaw, J.E.; Zimmet, P.Z. The metabolic syndrome: Prevalence in worldwide populations. Endocrinol. Metab. Clin. North Am., 2004, 33, 351-375.
[5]
Misra, A.; Khurana, L. Obesity and the metabolic syndrome in developing countries. J. Clin. Endocrinol. Metab., 2008, 93, S9-S30.
[6]
Isomaa, B.; Almgren, P.; Tuomi, T.; Forsen, B.; Lahti, K.; Nissen, M.; Taskinen, M.R.; Groop, L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care, 2001, 24, 683-689.
[7]
Malik, S.; Wong, N.D.; Franklin, S.S.; Kamath, T.V.; L’Italien, G.J.; Pio, J.R.; Williams, G.R. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation, 2004, 110, 1245-1250.
[8]
Daly, C.A.; Hildebrandt, P.; Bertrand, M.; Ferrari, R.; Remme, W.; Simoons, M.; Fox, K.M. EUROPA investigators. Adverse prognosis associated with the metabolic syndrome in established coronary artery disease: Data from the EUROPA trial. Heart, 2007, 93, 1406-1411.
[9]
Gami, A.S.; Witt, B.J.; Howard, D.E.; Erwin, P.J.; Gami, L.A.; Somers, V.K.; Montori, V.M. Metabolic syndrome and risk of incident cardiovascular events and death: A systematic review and meta-analysis of longitudinal studies. J. Am. Coll. Cardiol., 2007, 49, 403-414.
[10]
Sakamoto, N.; Nishiike, T.; Iguchi, H.; Sakamoto, K. Relationship between acute insulin response and vitamin K intake in healthy young male volunteers. Diabetes Nutr. Metab., 1999, 12, 37-41.
[11]
Yoshida, M.; Booth, S.L.; Meigs, J.B.; Saltzman, E.; Jacques, P.F. Phylloquinone intake, insulin sensitivity, and glycemic status in men and women. Am. J. Clin. Nutr., 2008, 88, 210-215.
[12]
Pan, Y.; Jackson, R.T. Dietary phylloquinone intakes and metabolic syndrome in US young adults. J. Am. Coll. Nutr., 2009, 28, 369-379.
[13]
Beulens, J.W. van der A, D.L.; Grobbee, D.E.; Sluijs, I.; Spijkerman, A.M.; van der Schouw, Y.T. Dietary phylloquinone and menaquinones intakes and risk of type 2 diabetes. Diabetes Care, 2010, 33, 1699-1705.
[14]
Ibarrola-Jurado, N.; Salas-Salvadó, J.; Martínez-González, M.A.; Bulló, M. Dietary phylloquinone intake and risk of type 2 diabetes in elderly subjects at high risk of cardiovascular disease. Am. J. Clin. Nutr., 2012, 96, 1113-1118.
[15]
Juanola-Falgarona, M.; Salas-Salvadó, J.; Estruch, R.; Portillo, M.P.; Casas, R.; Miranda, J.; Martínez-González, M.A.; Bulló, M. Association between dietary phylloquinone intake and peripheral metabolic risk markers related to insulin resistance and diabetes in elderly subjects at high cardiovascular risk. Cardiovasc. Diabetol., 2013, 12, 7.
[16]
Dam, V.; Dalmeijer, G.W.; Vermeer, C.; Drummen, N.E.; Knapen, M.H.; van der Schouw, Y.T.; Beulens, J.W. Association between vitamin K and the metabolic syndrome: A 10-year follow-up study in adults. J. Clin. Endocrinol. Metab., 2015, 100, 2472-2479.
[17]
Suttie, J.W. Vitamin K in health and disease, 1st ed; CRC Press: Florida, 2009.
[18]
Beulens, J.W.; Booth, S.L.; Van den Heuvel, E.G.H.M.; Stoecklin, E.; Baka, A.; Vermeer, C. The role of menaquinones (vitamin K2) in human health. Br. J. Nutr., 2013, 110, 1357-1368.
[19]
Shearer, M.; Fu, X.; Booth, S. Vitamin K nutrition, metabolism, and requirements: Current concepts and future research. Adv. Nutr., 2012, 2, 182-195.
[20]
Hara, K.; Akiyama, Y.; Nakamura, T.; Murota, S.; Morita, I. The inhibitory effect of vitamin K, (menatetrenone) on bone resorption may be related to its side chain. Bone, 1995, 16, 179-184.
[21]
Li, J.; Lin, J.C.; Wang, H.; Peterson, J.W.; Furie, B.C.; Furie, B.; Booth, S.L.; Volpe, J.J.; Rosenberg, P.A. Novel role of vitamin k in preventing oxidative injury to developing oligodendrocytes and neurons. J. Neurosci., 2003, 23, 5816-5826.
[22]
Kim, J.H.; Bachmann, R.A.; Chen, J. Interleukin-6 and insulin resistance. Vitam. Horm., 2009, 80, 613-633.
[23]
Hoene, M.; Weigert, C. The role of interleukin-6 in insulin resistance, body fat distribution and energy balance. Obes. Rev., 2008, 9, 20-29.
[24]
Moran, A.; Steffen, L.M.; Jacobs, D.R., Jr; Steinberger, J.; Pankow, J.S.; Hong, C.P.; Tracy, R.P.; Sinaiko, A.R. Relation of C-reactive protein to insulin resistance and cardiovascular risk factors in youth. Diabetes Care, 2005, 28, 1763-1768.
[25]
Ndumele, C.E.; Pradhan, A.D.; Ridker, P.M. Interrelationships between inflammation, C-reactive protein, and insulin resistance. J. Cardiometab. Syndr., 2006, 1, 190-196.
[26]
Gundberg, C.M.; Lian, J.B.; Booth, S.L. Vitamin K-dependent carboxylation of osteocalcin: Friend or foe? Adv. Nutr., 2012, 3, 149-157.
[27]
Ma, X.Y.; Chen, F.Q.; Hong, H.; Lv, X.J.; Dong, M.; Wang, Q.Y. The Relationship between Serum Osteocalcin Concentration and Glucose and Lipid Metabolism in Patients with Type 2 Diabetes Mellitus – The Role of Osteocalcin in Energy Metabolism. Ann. Nutr. Metab., 2015, 66, 110-116.
[28]
Shu, H.; Pei, Y.; Chen, K.; Lu, J. Significant inverse association between serum osteocalcin and incident type 2 diabetes in a middle-aged cohort. Diabetes Metab. Res. Rev., 2016, 32, 867-874.
[29]
Tirapelli, C.R.; Resstel, L.B.; de Oliveira, A.M.; Corrêa, F.M. Mechanisms underlying the biphasic effect of vitamin K1 (phylloquinone) on arterial blood pressure. J. Pharm. Pharmacol., 2008, 60, 889-893.
[30]
Takeuchi, Y.; Suzawa, M.; Fukumoto, S.; Fujita, T. Vitamin K(2) inhibits adipogenesis, osteoclastogenesis, and ODF/RANK ligand expression in murine bone marrow cell cultures. Bone, 2000, 27, 769-776.
[31]
Rees, K.; Guraewal, S.; Wong, Y.L.; Majanbu, D.L.; Mavrodaris, A.; Stranges, S.; Kandala, N.B.; Clarke, A.; Franco, O.H. Is vitamin K consumption associated with cardio-metabolic disorders? A systematic review. Maturitas, 2010, 67, 121-128.
[32]
Suksomboon, N.; Poolsup, N.; Ko Ko, H.D. Effect of vitamin K supplementation on insulin sensitivity: A meta-analysis. Diabetes Metab. Syndr. Obes., 2017, 10, 169-177.
[33]
Liberati, A.; Altman, D.G.; Tetzlaff, J.; Mulrow, C.; Gøtzsche, P.C.; Ioannidis, J.P.A.; Clarke, M.; Devereaux, P.J.; Kleijnen, J.; David, M. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration. BMJ, 2009, 339, b2700.
[34]
Deeks, J.J.; Higgins, J.P.T.; Altman, D.G. Analysing data and undertaking meta-analyses.In: Cochrane Handbook of Systemic Reviews of Interventions; Higgins, J.P.T.; Green, S., Eds.; John Wiley & Sons Ltd: Chichester, 2008, pp. 243-296.
[35]
Hozo, S.P.; Djulbegovic, B.; Hozo, I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med. Res. Methodol., 2005, 20, 13.
[36]
Aronne, L.J. Classification of obesity and assessment of obesity-related health risks. Obes. Res., 2002, 10, 105S-115S.
[37]
Nagasawa, Y.; Fujii, M.; Kajimoto, Y.; Imai, E.; Hori, M. Vitamin K2 and Serum cholesterol in patients on continuous ambulatory peritoneal dialysis. Lancet, 1998, 351, 724.
[38]
Nagasawa, Y.; Fujii, M.; Imai, E.; Hori, M. Author’s Reply to Vitamin K2 and Serum cholesterol in patients on continuous ambulatory peritoneal dialysis. Lancet, 1998, 351, 1735.
[39]
Sakamoto, N.; Nishiike, T.; Iguchi, H.; Sakamoto, K. Possible effects of one week vitamin K (menaquinone-4) tablets intake on glucose tolerance in healthy young male volunteers with different descarboxy prothrombin levels. Clin. Nutr., 2000, 19, 259-263.
[40]
Shin, C. Effect of Vitamin K Supplementation on Glucose Metabolism., https://clinicaltrials.gov/ct2/show/NCT00960973?term=Vitamin+K%2Cphylloquinone%2C+menaquinone&cond=Diabetes&rank=4 (Accessed on September 11, 2017).
[41]
Pollock, N. Vitamin K and Glucose Metabolism in Adults at Risk for Diabetes (Vita-K ' n ' Adults Study). https://clinicaltrials.gov/ct2/show/NCT02366481?term=Vitamin+K%2Cphylloquinone%2C+menaquinone&cond=Diabetes&rank=3 (Accessed on September 11, 2017).
[42]
Rasekhi, H.; Karandish, M.; Jalali, M.; Mohammadshahi, M.; Zarei, M.; Saki, A.; Shahbazian, H. Phylloquinone supplementation improves glycemic status independent of the effects of adiponectin levels in premonopause women with prediabetes: a double-blind randomized controlled clinical trial. J. Diabetes Metab. Disord., 2015, 14, 1.
[43]
Rasekhi, H.; Karandish, M.; Jalali, M.T.; Mohammad-Shahi, M.; Zarei, M.; Saki, A.; Shahbazian, H. The effect of vitamin K1 supplementation on sensitivity and insulin resistance via osteocalcin in prediabetic women: A double-blind randomized controlled clinical trial. Eur. J. Clin. Nutr., 2015, 69, 891-895.
[44]
Yoshida, M.; Jacques, P.F.; Meigs, J.B.; Saltzman, E.; Shea, M.K.; Gundberg, C.; Dawson-Hughes, B.; Dallal, G.; Booth, S.L. Effect of vitamin K supplementation on insulin resistance in older men and women. Diabetes Care, 2008, 31, 2092-2096.
[45]
Kristensen, M.; Kudsk, J.; Bugel, S. Six weeks phylloquinone supplementation produces undesirable effects on blood lipids with no changes in inflammatory and fibrinolytic markers in postmenopausal women. Eur. J. Nutr., 2008, 47, 375-379.
[46]
Shea, M.K.; Dallal, G.E.; Dawson-Hughes, B.; Ordovas, J.M.; O’Donnell, C.J.; Gundberg, C.M.; Peterson, J.W.; Booth, S.L.; Vitamin, K. circulating cytokines, and bone mineral density in older men and women. Am. J. Clin. Nutr., 2008, 88, 356-363.
[47]
Shea, M.K.; O’Donnell, C.J.; Hoffmann, U.; Dallal, G.E.; Dawson-Hughes, B.; Ordovas, J.M.; Price, P.A.; Williamson, M.K.; Booth, S.L. Vitamin K supplementation and progression of coronary artery calcium in older men and women. Am. J. Clin. Nutr., 2009, 89, 1799-1807.
[48]
Koitaya, N.; Ezaki, J.; Nishimuta, M.; Yamauchi, J.; Hashizume, E.; Morishita, K.; Miyachi, M.; Sasaki, S.; Ishimi, Y. Effect of low dose vitamin K2 (MK-4) supplementation on bio- indices in postmenopausal japanese women. J. Nutr. Sci. Vitaminol., 2009, 55, 15-21.
[49]
Kumar, R.; Binkley, N.; Vella, A. Effect of phylloquinone supplementation on glucose homeostasis in humans. Am. J. Clin. Nutr., 2010, 92, 1528-1532.
[50]
Sang, H.; Joo, N.S.; Choi, B.; Kim, K.; Kim, B.; Park, S.; Cho, Y.; Kim, K.; Lee, D. vitamin K supplement along with vitamin D and calcium reduced serum concentration of undercarboxylated osteocalcin while increasing bone mineral density in Korean postmenopausal women over sixty-years-old. J. Korean Med. Sci., 2011, 26, 1093-1098.
[51]
Choi, H.J.; Yu, J.; Choi, H.; An, J.H.; Kim, S.W.; Park, K.S.; Jang, H.C.; Kim, S.Y.; Shin, C.S. Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial. Diabetes Care, 2011, 34, e147.
[52]
Fulton, R.L.; McMurdo, M.E.T.; Hill, A.; Abboud, R.J.; Arnold, G.P.; Struthers, A.D.; Khan, F.; Witham, M.D. Vitamin K to improve markers of vascular health and physical function in older people with vascular disease -a randomised controlled trial. Age Ageing, 2014, 43, ii14.
[53]
Kurnatowska, I.; Grzelak, P.; Masajtis-Zagajewska, A.; Kaczmarska, M.; Stefańczyk, L.; Vermeer, C.; Maresz, K.; Nowicki, M. Effect of vitamin K2 on progression of atherosclerosis and vascular calcification in nondialyzed patients with chronic kidney disease stages 3-5. Pol. Arch. Med. Wewn., 2015, 12, 631-640.
[54]
Kolahi, S.; Gargari, B.P.; Abbasi, M.M.; Jafarabadi, M.A.; Shishavan, N.G. Effects of phylloquinone supplementation on lipid profile in women with rheumatoid arthritis: a double blind placebo controlled study. Nutr. Res. Pract., 2015, 9, 186-191.
[55]
Fulton, R.L.; McMurdo, M.E.; Hill, A.; Abboud, R.J.; Arnold, G.P.; Struthers, A.D.; Khan, F.; Vermeer, C.; Knapen, M.H.; Drummen, N.E.; Witham, M.D. Effect of vitamin K on vascular health and physical function in older people with vascular disease--a randomised controlled trial. J. Nutr. Health Aging, 2016, 20, 325-333.
[56]
Pollock, N. Vitamin K and glucose metabolism in children at risk for diabetes (vita-K 'n' kids study). https://clinicaltrials.gov/ct2/show/NCT01972113?term=Vitamin+K%2Cphylloquinone%2C+menaquinone&cond=Diabetes&rank=1 (Accessed on September 16, 2017).
[57]
Pollock, N. Vitamin K to slow progression of dyslipidemia and diabetes risk (vita-K 'n' kids study ii). https://clinicaltrials.gov/ct2/show/NCT02959762?term=Vitamin+K%2Cphylloquinone%2C+menaquinone&cond=Diabetes&rank=2 (Accessed on September 16, 2017).
[58]
Pollock, N.K.; Nguyen, J.; Fain, M.E.; Gower, B.A.; Bassali, R.; Davis, C.L. Menaquinone-7 supplementation improves lipid profile in obese african-american children: A randomized controlled trial. FASEB 30, 2016, 423-426.

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