Effect of Vitamin K Supplementation on Glycemic Control: A Systematic Review and Meta-Analysis of Clinical Trials

Abstract

Type 2 diabetes mellitus (T2DM) is one of the most important public health issues. Vitamin K supplementation might have favorable effect on risk factors of T2DM. The aim of this study was to perform a systematic review and meta-analysis of interventional studies to examine the effect of vitamin K supplementation on glycemic indices. A systematic search was performed in electronic databases including PubMed, Science Direct, ProQuest, Institute of Scientific Information Web of Science, and Google scholar up to July 2017. We used a random effects model to estimate pooled effect size of fasting blood sugar (FBS), 2-h oral glucose tolerance test (2-h OGTT), fasting insulin (FINS), and homeostasis model assessment-estimated insulin resistance (HOMA-IR). Five clinical trials (533 participants) fulfilled the eligibility criteria of the present meta-analysis. Overall, meta-analysis could not show any beneficial effect of vitamin K supplementation on FBS (–0.91 mg/dl, 95% CI: –2.57, 0.76, p=0.28), FINS (–0.35 μIU/ml, 95% CI: –1.70, 1.00, p=0.61), HOMA-IR (–0.06, 95% CI: –0.32, –0.19, p=0.63), and 2-h OGTT (–4.00 mg/dl, 95% CI: –20.00, 11.99, p=0.62). Sensitivity analysis showed that overall estimates were not affected by elimination of any study. We did not observe any evidence regarding publication bias. In conclusion, vitamin K supplementation had no significant effect on glycemic control in healthy subjects. However, further studies should be performed on diabetic and pre-diabetic patients to determine the effect of vitamin K supplementation on impaired glycemic control.

Key words

vitamin K - fasting blood sugar - serum insulin - glycemic control - meta-analysis

• References

• 1 Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus – present and future perspectives. Nat Rev Endocrinol 2012; 8: 228-236
• 2 Roglic G. WHO Global report on diabetes: A summary. Int J Non-Commun Dis 2016; 1: 3
• 3 Ardisson Korat AV, Willett WC, Hu FB. Diet, lifestyle, and genetic risk factors for type 2 diabetes: A review from the nurses’ health study, nurses’ health study 2, and health professionals’ follow-up study. Curr Nutr Rep 2014; 3: 345-354
• 4 InterAct Consortium. Romaguera D, Norat T, Wark PA, Vergnaud AC, Schulze MB, van Woudenbergh GJ, Drogan D, Amiano P, Molina-Montes E, Sánchez MJ, Balkau B, Barricarte A, Beulens JW, Clavel-Chapelon F, Crispim SP, Fagherazzi G, Franks PW, Grote VA, Huybrechts I, Kaaks R, Key TJ, Khaw KT, Nilsson P, Overvad K, Palli D, Panico S, Quirós JR, Rolandsson O, Sacerdote C, Sieri S, Slimani N, Spijkerman AM, Tjonneland A, Tormo MJ, Tumino R, van den Berg SW, Wermeling PR, Zamara-Ros R, Feskens EJ, Langenberg C, Sharp SJ, Forouhi NG, Riboli E, Wareham NJ. Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct. Diabetologia 2013; 56: 1520-1530
• 5 Ley SH, Hamdy O, Mohan V, Hu FB. Prevention and management of type 2 diabetes: dietary components and nutritional strategies. Lancet 2014; 383: 1999-2007
• 6 Dong JY, Xun P, He K, Qin LQ. Magnesium intake and risk of type 2 diabetes meta-analysis of prospective cohort studies. Diabetes Care 2011; 34: 2116-2122
• 7 Mitri J, Muraru MD, Pittas AG. Vitamin D and type 2 diabetes: A systematic review. Eur J Clin Nutr 2011; 65: 1005-1015
• 8 Sun Q, van Dam RM, Willett WC, Hu FB. Prospective study of zinc intake and risk of type 2 diabetes in women. Diabetes Care 2009; 32: 629-634
• 9 Park K, Rimm EB, Siscovick DS, Spiegelman D, Manson JE, Morris JS, Hu FB, Mozaffarian D. Toenail selenium and incidence of type 2 diabetes in U.S. men and women. Diabetes Care 2012; 35: 1544-1551
• 10 Manna P, Kalita J. Beneficial role of vitamin K supplementation on insulin sensitivity, glucose metabolism, and the reduced risk of type 2 diabetes: A review. Nutrition 2016; 32: 732-739
• 11 Shearer MJ. Chemistry, nutritional sources, tissue distribution and metabolism of vitamin K with special reference to bone health. J Nutr 1996; 126: 1181S
• 12 Booth SL. Vitamin K: food composition and dietary intakes. Food Nutr Res 2012; 56 [Epub 2012 Apr 2]
• 13 Huang ZB, Wan SL, Lu YJ, Ning L, Liu C, Fan SW. Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials. Osteoporos Int 2015; 26: 1175-1186
• 14 Schurgers LJ, Cranenburg ECM, Vermeer C. Matrix Gla-protein: The calcification inhibitor in need of vitamin K. Thromb Haemost. 2008; 100: 593-603
• 15 Vermeer C. Vitamin K: the effect on health beyond coagulation-an overview. Food Nutr Res 2012; 56 [Epub 2012 Apr 2]
• 16 Rasekhi H, Karandish M, Jalali MT, 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
• 17 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
• 18 Choi HJ, Yu J, Choi H, An JH, Kim SW, Park KS, Hak JC, Kim SY, Shin CS. Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: A placebo-controlled trial. Diabetes Care 2011; 34: e147
• 19 Moher D, Liberati A, Tetzlaff J, Altman DG, The PG. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA Statement. PLoS Med 2009; 6: e1000097
• 20 Asemi Z, Raygan F, Bahmani F, Rezavandi Z, Talari HR, Rafiee M, Poladchang S, Darooghegi Mofrad M, Taheri S, Mohammadi AA, Esmaillzadeh A. The effects of vitamin D, K and calcium co-supplementation on carotid intima-media thickness and metabolic status in overweight type 2 diabetic patients with CHD. Br J Nutr 2016; 116: 286-293
• 21 Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials 1996; 17: 1-12
• 22 Moher D, Schulz KF, Altman DG. The CONSORT statement: Revised recommendations for improving the quality of reports of parallel group randomized trials. BMC Med Res Methodol 2001; 1: 2
• 23 Centi AJ. Association of vitamin K with insulin resistance and body composition (Order No. 3701851). 2015; Available from Biological Science Database; ProQuest Dissertations & Theses Global (1682048195). Retrieved from https://search.proquest.com/docview/1682048195?accountid = 41305
• 24 Yoshida M, Jacques PF, Meigs JB, Saltzman E, Shea MK, Gundberg C, Dawson-Hughes B, Dallal G, Booth SL. Effect of vitamin K supplementation on insulin resistance in older men and women. Diabetes Care 2008; 31: 2092-2096
• 25 Kumar R, Binkley N, Vella A. Effect of phylloquinone supplementation on glucose homeostasis in humans. Am J Clin Nutr. 2010; 92: 1528-1532
• 26 Beulens JW, Grobbee DE, Sluijs I, Spijkerman AM, Van Der Schouw YT. Dietary phylloquinone and menaquinones intakes and risk of type 2 diabetes. Diabetes Care 2010; 33: 1699-1705
• 27 Iwamoto J, Seki A, Sato Y, Matsumoto H, Takeda T, Yeh JK. Vitamin K2 prevents hyperglycemia and cancellous osteopenia in rats with streptozotocin-induced type 1 diabetes. Calcif Tissue Int 2011; 88: 162-168
• 28 Varsha MS, Raman T, Manikandan R, Dhanasekaran G. Hypoglycemic action of vitamin K1 protects against early-onset diabetic nephropathy in streptozotocin-induced rats. Nutrition 2015; 31: 1284-1292
• 29 Varsha MS, Thiagarajan R, Manikandan R, Dhanasekaran G. Vitamin K1 alleviates streptozotocin-induced type 1 diabetes by mitigating free radical stress, as well as inhibiting NF-κB activation and iNOS expression in rat pancreas. Nutrition 2015; 31: 214-222
• 30 Manna P, Kalita J. Beneficial role of vitamin K supplementation on insulin sensitivity, glucose metabolism, and the reduced risk of type 2 diabetes: a review. Nutrition 2016; 32: 732-739
• 31 Yoshida M, Booth SL, Meigs JB, Saltzman E, Jacques PF. Phylloquinone intake, insulin sensitivity, and glycemic status in men and women. Am J Clin Nutr 2008; 88: 210-215
• 32 Ibarrola-Jurado N, Salas-Salvadó J, Martínez-González MA, 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
• 33 Dam V, Dalmeijer GW, Vermeer C, Drummen NE, Knapen MH, van der Schouw YT, Beulens JW. Association between vitamin K and the metabolic syndrome: A 10-year follow-up study in adults. J Clin Endocrinol Metab 2015; 100: 2472-2479
• 34 Pan Y, Jackson RT. Dietary phylloquinone intakes and metabolic syndrome in US young adults. J Am Coll Nutr. 2009; 28: 369-379
• 35 Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α- and obesity-induced insulin resistance. Science 1996; 271: 665-668
• 36 Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006; 444: 860-867
• 37 Reddi K, Henderson B, Meghji S, Wilson M, Poole S, Hopper C, Harris M, Hodges SJ. Interleukin 6 production by lipopolysaccharide-stimulated human fibroblasts is potently inhibited by Naphthoquinone (vitamin K) compounds. Cytokine 1995; 7: 287-290
• 38 Shea MK, Dallal GE, Dawson-Hughes B, Ordovas JM, O'Donnell CJ, Gundberg CM, Peterson JW, Booth SL. Vitamin K, circulating cytokines, and bone mineral density in older men and women. Am J Clin Nutr 2008; 88: 356-363
• 39 Ye R, Scherer PE. Adiponectin, driver or passenger on the road to insulin sensitivity?. Mol Metab 2013; 2: 133-141
• 40 Ouchi N, Walsh K. Adiponectin as an anti-inflammatory factor. Clin Chim Acta 2007; 380: 24-30
• 41 Ohashi K, Ouchi N, Matsuzawa Y. Anti-inflammatory and anti-atherogenic properties of adiponectin. Biochimie 2012; 94: 2137-2142
• 42 Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001; 7: 941-946
• 43 Kharroubi I, Rasschaert J, Eizirik DL, Cnop M. Expression of adiponectin receptors in pancreatic β cells. Biochem Biophys Res Commun 2003; 312: 1118-1122
• 44 Vollenweider P, von Eckardstein A, Widmann C. HDLs, Diabetes, and metabolic syndrome. Handb Exp Pharmacol 2015; 224: 405-421
• 45 Kawashima H, Nakajima Y, Matubara Y, Nakanowatari J, Fukuta T, Mizuno S, Takahashi S, Tajima T, Nakamura T. Effects of vitamin K2 (menatetrenone) on atherosclerosis and blood coagulation in hypercholesterolemic rabbits. Jpn J Pharmacol 1997; 75: 135-143
• 46 Sogabe N, Maruyama R, Baba O, Hosoi T, Goseki-Sone M. Effects of long-term vitamin K1 (phylloquinone) or vitamin K2 (menaquinone-4) supplementation on body composition and serum parameters in rats. Bone 2011; 48: 1036-1042
• 47 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
• 48 Booth SL, Centi A, Smith SR, Gundberg C. The role of osteocalcin in human glucose metabolism: Marker or mediator?. Nat Rev Endocrinol 2013; 9: 43-55
• 49 Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G. Endocrine regulation of energy metabolism by the skeleton. Cell 2007; 130: 456-469
• 50 Ferron M, Hinoi E, Karsenty G, Ducy P. Osteocalcin differentially regulates β cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci U S A 2008; 105: 5266-5270
• 51 Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B. Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 2009; 94: 827-832
• 52 Saleem U, Mosley TH, Kullo IJ. Serum osteocalcin is associated with measures of insulin resistance, adipokine levels, and the presence of metabolic syndrome. Arterioscler Thromb Vasc Biol 2010; 30: 1474-1478
• 53 Kimmons JE, Blanck HM, Tohill BC, Zhang J, Khan LK. Associations Between Body Mass Index and the Prevalence of Low Micronutrient Levels Among US Adults. MedGenMed 2006; 8: 59