Abstract
This systematic review and meta-analysis assessed the antidiabetic effect of pharmaconutrients as an add-on in type 2 diabetes mellitus patients by pooling data from currently available randomized controlled trials (RCTs). Data sources included the PubMed and EMBASE, Cochrane Central Register of Controlled Trials. RCTs reporting changes in glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), or homeostasis model assessment of insulin resistance (HOMA-IR) levels following add-on pharmaconutritional therapies for T2DM patients consuming antidiabetic drugs were targeted. Using random-effects meta-analyses, we identified pharmaconutrients with effects on glycemic outcomes. Heterogeneity among studies was presented using I2 values. Among 9537 articles, 119 RCTs with nine pharmaconutrients (chromium; coenzyme Q10; omega-3 fatty acids; vitamins C, D, and E; alpha-lipoic acid; selenium; and zinc) were included. Chromium (HbA1c, FBG, and HOMA-IR), coenzyme Q10 (HbA1c and FBG), vitamin C (HbA1c and FBG), and vitamin E (HbA1c and HOMA-IR) significantly improved glycemic control. Baseline HbA1c level and study duration influenced the effects of chromium and vitamin E on HbA1c level. Sensitivity analyses did not modify the pooled effects of pharmaconutrients on glycemic control. Administration of chromium, coenzyme Q10, and vitamins C and E for T2DM significantly improved glycemic control. This study has been registered in PROSPERO (CRD42018115229).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
Data described in the manuscript will be made publicly and freely available without restriction in PUBMED, MEDLINE, and other related website.
References
Abraham AS, Brooks BA, Eylath U (1992) The effects of chromium supplementation on serum glucose and lipids in patients with and without non-insulin-dependent diabetes. Metabolism 41:768–771. https://doi.org/10.1016/0026-0495(92)90318-5
Afkhami-Ardekani M, Karimi M, Mohammad MS, Nourani F (2008) Effect of zinc sulfate supplementation on lipid and glucose in type 2 diabetic patients. Pak J Nutr 7:550–553. https://doi.org/10.3923/pjn.2008.550.553
Ahmadi N, Mortazavi M, Iraj B, Askari G (2013) Whether vitamin D3 is effective in reducing proteinuria in type 2 diabetic patients? J Res Med Sci 18:374–377. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810568/
Akbari-Fakhrabadi M, Zeinali Ghotrom A, Mozaffari-Khosravi H, Hadi Nodoushan H, Nadjarzadeh A (2014) Effect of coenzyme Q10 on oxidative stress, glycemic control and inflammation in diabetic neuropathy: a double blind randomized clinical trial. Int J Vitam Nutr Res 84:252–260. https://doi.org/10.1024/0300-9831/a000211
Al-Sofiani ME, Jammah A, Racz M, Khawaja RA, Hasanato R, El-Fawal HA, Mousa SA, Mason DL (2015) Effect of vitamin D supplementation on glucose control and inflammatory response in type II diabetes: a double blind, randomized clinical trial. Int J Endocrinol Metab 13:e22604. https://doi.org/10.5812/ijem.22604
Al-Zahrani MK, Elnasieh AM, Alenezi FM, Almoushawah AA, Almansour M, Alshahrani F, Rahman SU, Al-Zahrani A (2014) A 3-month oral vitamin D supplementation marginally improves diastolic blood pressure in Saudi patients with type 2 diabetes mellitus. Int J Clin Exp Med 7:5421–5428. https://pubmed.ncbi.nlm.nih.gov/25664051/
Angellotti E, D’Alessio D, Dawson-Hughes B, Nelson J, Cohen RM, Gastaldelli A, Pittas AG (2018) Vitamin D supplementation in patients with type 2 diabetes: the vitamin D for established type 2 diabetes (DDM2) study. J Endocr Soc 2:310–321. https://doi.org/10.1210/js.2018-00015
Ansar H, Mazloom Z, Kazemi F, Hejazi N (2011) Effect of alpha-lipoic acid on blood glucose, insulin resistance and glutathione peroxidase of type 2 diabetic patients. Saudi Med J 32:584–588. https://pubmed.ncbi.nlm.nih.gov/21666939/
Ansari S, Djalali M, Mohammadzadeh Honarvar N, Mazaherioun M, Zarei M, Agh F, Gholampour Z, Javanbakht MH (2017) The effect of n-3 polyunsaturated fatty acids supplementation on serum irisin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Int J Endocrinol Metab 15:e40614. https://doi.org/10.5812/ijem.40614
Anyanwu AC, Fasanmade OA, Odeniyi IA, Iwuala S, Coker HB, Ohwovoriole AE (2016) Effect of vitamin D supplementation on glycemic control in type 2 diabetes subjects in Lagos, Nigeria. Indian J Endocrinol Metab 20:189–194. https://doi.org/10.4103/2230-8210.176345
Asbaghi O, Fatemeh N, Mahnaz RK, Ehsan G, Elham E, Behzad N, Damoon AL, Amirmansour AN (2020) Effects of chromium supplementation on glycemic control in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 161:105098. https://doi.org/10.1016/j.phrs.2020.105098
Ashor AW, Werner AD, Lara J, Willis ND, Mathers JC, Siervo M (2017) Effects of vitamin C supplementation on glycaemic control: a systematic review and meta-analysis of randomised controlled trials. Eur J Clin Nutr 71:1371–1380. https://doi.org/10.1038/ejcn.2017.24
Ayesha I, Raghunath M, Sesikeran B, Raghuramulu N (1998) Effect of oral administration of vitamin D on glucose tolerance and insulin secretion in type 2 diabetes mellitus. Diabetes Nutr Metab. 11:261–265
Bahijiri SM, Mira SA, Mufti AM, Ajabnoor MA (2000) The effects of inorganic chromium and brewer’s yeast supplementation on glucose tolerance, serum lipids and drug dosage in individuals with type 2 diabetes. Saudi Med J 21:831–837. https://pubmed.ncbi.nlm.nih.gov/11376359/
Baliarsingh S, Beg ZH, Ahmad J (2005) The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia. Atherosclerosis 182:367–374. https://doi.org/10.1016/j.atherosclerosis.2005.02.020
Balk EM, Earley A, Patel K, Trikalinos TA, Dahabreh IJ (2012) Empirical assessment of within-arm correlation imputation in trials of continuous outcomes. AHRQ methods for effective health care Agency for Healthcare Research and Quality, Rockville
Bartlett HE, Eperjesi F (2008) Nutritional supplementation for type 2 diabetes: a systematic review. Ophthalmic Physiol Opt 28:503–523. https://doi.org/10.1111/j.1475-1313.2008.00595.x
Bhatt JK, Thomas S, Nanjan MJ (2012) Effect of oral supplementation of vitamin C on glycemic control and lipid profile in patients with type 2 diabetes mellitus. Int J Pharm Pharm Sci 4:524–527.
Ble-Castillo JL, Carmona-Díaz E, Méndez JD, Larios-Medina FJ, Medina-Santillán R, Cleva-Villanueva G, Díaz-Zagoya JC (2005) Effect of alpha-tocopherol on the metabolic control and oxidative stress in female type 2 diabetics. Biomed Pharmacother 59:290–295. https://doi.org/10.1016/j.biopha.2005.05.002
Borkman M, Chisholm DJ, Furler SM, Storlien LH, Kraegen EW, Simons LA, Chesterman CN (1989) Effects of fish oil supplementation on glucose and lipid metabolism in NIDDM. Diabetes 38:1314–1319. https://doi.org/10.2337/diab.38.10.1314
Boshtam M, Rafiei M, Golshadi ID, Ani M, Shirani Z, Rostamshirazi M (2005) Long term effects of oral vitamin E supplement in type II diabetic patients. Int J Vitam Nutr Res 75:341–346. https://doi.org/10.1024/0300-9831.75.5.341
Breslavsky A, Frand J, Matas Z, Boaz M, Barnea Z, Shargorodsky M (2013) Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients. Clin Nutr 32:970–975. https://doi.org/10.1016/j.clnu.2013.01.020
Chen H, Karne RJ, Hall G, Campia U, Panza JA, Cannon RO 3rd, Wang Y, Katz A, Levine M, Quon MJ (2006) High-dose oral vitamin C partially replenishes vitamin C levels in patients with type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance. Am J Physiol Heart Circ Physiol 290:H137–H145. https://doi.org/10.1152/ajpheart.00768.2005
Chen YL, Lin JD, Hsia TL, Mao FC, Hsu CH, Pei D (2014) The effect of chromium on inflammatory markers, 1st and 2nd phase insulin secretion in type 2 diabetes. Eur J Nutr 53:127–133. https://doi.org/10.1007/s00394-013-0508-8
Chen C, Yu X, Shao S (2015) Effects of omega-3 fatty acid supplementation on glucose control and lipid levels in type 2 diabetes: a meta-analysis. PLoS ONE 10:e0139565. https://doi.org/10.1371/journal.pone.0139565
Chew GT, Watts GF (2004) Coenzyme Q10 and diabetic endotheliopathy: oxidative stress and the ‘recoupling hypothesis.’ QJM 97:537–548. https://doi.org/10.1093/qjmed/hch089
Chew GT, Watts GF, Davis TM, Stuckey BG, Beilin LJ, Thompson PL, Burke V, Currie PJ (2008) Hemodynamic effects of fenofibrate and coenzyme Q10 in type 2 diabetic subjects with left ventricular diastolic dysfunction. Diabetes Care 31:1502–1509. https://doi.org/10.2337/dc08-0118
Dakhale GN, Chaudhari HV, Shrivastava M (2011) Supplementation of vitamin C reduces blood glucose and improves glycosylated hemoglobin in type 2 diabetes mellitus: a randomized, double-blind study. Adv Pharmacol Sci 2011:195271. https://doi.org/10.1155/2011/195271
Dalan R, Liew H, Assam PN, Chan ES, Siddiqui FJ, Tan AW, Chew DE, Boehm BO, Leow MK (2016) A randomised controlled trial evaluating the impact of targeted vitamin D supplementation on endothelial function in type 2 diabetes mellitus: the DIMENSION trial. Diab Vasc Dis Res 13:192–200. https://doi.org/10.1177/1479164115621667
Dass AS, Narayana S, Venkatarathnamma PN (2018) Effect of vitamin E and omega 3 fatty acids in type 2 diabetes mellitus patients. J Adv Pharm Technol Res 9:32–36. https://doi.org/10.4103/japtr.JAPTR_309_17
Davì G, Santilli F, Patrono C (2010) Nutraceuticals in diabetes and metabolic syndrome. Cardiovasc Ther 28:216–226. https://doi.org/10.1111/j.1755-5922.2010.00179.x
de Jager J, Kooy A, Lehert P, Wulffelé MG, van der Kolk J, Bets D, Verburg J, Donker AJ, Stehouwer CD (2010) Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B12 deficiency: randomised placebo controlled trial. BMJ 340:c2181. https://doi.org/10.1136/bmj.c2181
de Oliveira AM, Rondó PH, Luzia LA, D’Abronzo FH, Illison VK (2011) The effects of lipoic acid and alpha-tocopherol supplementation on the lipid profile and insulin sensitivity of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Diabetes Res Clin Pract 92:253–260. https://doi.org/10.1016/j.diabres.2011.02.010
Economides PA, Khaodhiar L, Caselli A, Caballero AE, Keenan H, Bursell SE, King GL, Johnstone MT, Horton ES, Veves A (2005) The effect of vitamin E on endothelial function of micro- and macrocirculation and left ventricular function in type 1 and type 2 diabetic patients. Diabetes 54:204–211. https://doi.org/10.2337/diabetes.54.1.204
Eftekhari MH, Akbarzadeh M, Dabbaghmanesh MH, Hasanzadeh J (2011) Impact of treatment with oral calcitriol on glucose indices in type 2 diabetes mellitus patients. Asia Pac J Clin Nutr 20:521–526. https://pubmed.ncbi.nlm.nih.gov/22094836/
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634. https://doi.org/10.1136/bmj.315.7109.629
El-Aal AA, El-Ghffar EAA, Ghali AA, Zughbur MR, Sirdah MM (2018) The effect of vitamin C and/or E supplementations on type 2 diabetic adult males under metformin treatment: A single-blinded randomized controlled clinical trial. Diabetes Metab Syndr 12:483–489. https://doi.org/10.1016/j.dsx.2018.03.013
Elkassaby S, Harrison LC, Mazzitelli N, Wentworth JM, Colman PG, Spelman T, Fourlanos S (2014) A randomised controlled trial of high dose vitamin D in recent-onset type 2 diabetes. Diabetes Res Clin Pract 106:576–582. https://doi.org/10.1016/j.diabres.2014.08.030
Ellulu MS, Rahmat A, Ismail P, Khaza’ai H, Abed Y (2015) Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial. Drug Des Dev Ther 9:3405–3412. https://doi.org/10.2147/dddt.S83144
Elmarakby AA, Sullivan JC (2012) Relationship between oxidative stress and inflammatory cytokines in diabetic nephropathy. Cardiovasc Ther 30:49–59. https://doi.org/10.1111/j.1755-5922.2010.00218.x
Eriksson JG, Forsén TJ, Mortensen SA, Rohde M (1999) The effect of coenzyme Q10 administration on metabolic control in patients with type 2 diabetes mellitus. BioFactors 9:315–318. https://doi.org/10.1002/biof.5520090229
Evans M, Anderson RA, Smith JC, Khan N, Graham JM, Thomas AW, Morris K, Deely D, Frenneaux MP, Davies JS, Rees A (2003) Effects of insulin lispro and chronic vitamin C therapy on postprandial lipaemia, oxidative stress and endothelial function in patients with type 2 diabetes mellitus. Eur J Clin Investig 33:231–238. https://doi.org/10.1046/j.1365-2362.2003.01120.x
Evert AB, Boucher JL, Cypress M, Dunbar SA, Franz MJ, Mayer-Davis EJ, Neumiller JJ, Nwankwo R, Verdi CL, Urbanski P, Yancy WS (2014) Nutrition therapy recommendations for the management of adults with diabetes. Diabetes Care 37(suppl 1):S120–S143. https://doi.org/10.2337/dc14-S120
Faghihi T, Radfar M, Barmal M, Amini P, Qorbani M, Abdollahi M, Larijani B (2014) A randomized, placebo-controlled trial of selenium supplementation in patients with type 2 diabetes: effects on glucose homeostasis, oxidative stress, and lipid profile. Am J Ther 21:491–495. https://doi.org/10.1097/MJT.0b013e318269175f
Farrokhian A, Bahmani F, Taghizadeh M, Mirhashemi SM, Aarabi MH, Raygan F, Aghadavod E, Asemi Z (2016) Selenium supplementation affects insulin resistance and serum hs-CRP in patients with type 2 diabetes and coronary heart disease. Horm Metab Res 48:263–268. https://doi.org/10.1055/s-0035-1569276
Farrokhian A, Mahmoodian M, Bahmani F, Amirani E, Shafabakhsh R, Asemi Z (2019) The influences of chromium supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease. Biol Trace Elem Res 194(2):313–320. https://doi.org/10.1007/s12011-019-01783-7
Farsi PF, Djazayery A, Eshraghian MR, Koohdani F, Saboor-Yaraghi AA, Derakhshanian H, Zarei M, Javanbakht MH, Djalali M (2014) Effects of supplementation with omega-3 on insulin sensitivity and non-esterified free fatty acid (NEFA) in type 2 diabetic patients. Arq Bras Endocrinol Metab 58:335–340. https://doi.org/10.1590/0004-2730000002861
Fattore E, Botta F, Agostoni C, Bosetti C (2017) Effects of free sugars on blood pressure and lipids: a systematic review and meta-analysis of nutritional isoenergetic intervention trials. Am J Clin Nutr 105:42–56. https://doi.org/10.3945/ajcn.116.139253
Florkowski C (2013) HbA1c as a diagnostic test for diabetes mellitus: reviewing the evidence. Clin Biochem Rev 34:75–83. https://pubmed.ncbi.nlm.nih.gov/24151343/
Gazis A, White DJ, Page SR, Cockcroft JR (1999) Effect of oral vitamin E (alpha-tocopherol) supplementation on vascular endothelial function in type 2 diabetes mellitus. Diabet Med 16:304–311. https://doi.org/10.1046/j.1464-5491.1999.00049.x
Ghaffari P, Nadiri M, Gharib A, Rahimi F (2015) The effects of vitamin C on diabetic patients. Pharm Lett 7:68–71. https://www.scholarsresearchlibrary.com/articles/the-effects-of-vitamin-c-on-diabetic-patients.pdf
Ghavamzadeh S, Mobasseri M, Mahdavi R (2014) The effect of vitamin D supplementation on adiposity, blood glycated hemoglobin, serum leptin and tumor necrosis factor-alpha in type 2 diabetic patients. Int J Prev Med 5:1091–1098. https://doaj.org/article/4752b1a74de84f83bdabfc925f32f20e
Gholami M, Rezvanfar MR, Delavar M, Abdollahi M, Khosrowbeygi A (2019) Effects of coenzyme Q10 supplementation on serum values of gamma-glutamyl transferase, pseudocholinesterase, bilirubin, ferritin, and high-sensitivity C-reactive protein in women with type 2 diabetes. Exp Clin Endocrinol Diabetes 127:311–319. https://doi.org/10.1055/s-0043-124183
Ghosh D, Bhattacharya B, Mukherjee B, Manna B, Sinha M, Chowdhury J, Chowdhury S (2002) Role of chromium supplementation in Indians with type 2 diabetes mellitus. J Nutr Biochem 13:690–697. https://doi.org/10.1016/s0955-2863(02)00220-6
Golzari MH, Hosseini S, Koohdani F, Saboor Yaraghi AA, Javanbakht MH, Mohammadzadeh-Honarvar N, Djalali M (2017) The effect of eicosapentaenoic acid on the serum levels and enzymatic activity of paraoxonase 1 in the patients with type 2 diabetes mellitus. Acta Med Iran 55:486–495. https://doaj.org/article/828ce19f09bb46dba1b29a6a85858dcd
Gomes PM, Hollanda-Miranda WR, Beraldo RA, Castro AV, Geloneze B, Foss MC, Foss-Freitas MC (2015) Supplementation of alpha-linolenic acid improves serum adiponectin levels and insulin sensitivity in patients with type 2 diabetes. Nutrition 31:853–857. https://doi.org/10.1016/j.nut.2014.12.028
Guimarães MM, Martins Silva Carvalho AC, Silva MS (2013) Chromium nicotinate has no effect on insulin sensitivity, glycemic control, and lipid profile in subjects with type 2 diabetes. J Am Coll Nutr 32:243–250. https://doi.org/10.1080/07315724.2013.816598
Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schünemann HJ, GRADE Working Group (2008) What is ‘quality of evidence’ and why is it important to clinicians? BMJ 336:995–998. https://doi.org/10.1136/bmj.39490.551019.BE
Hamilton SJ, Chew GT, Watts GF (2009) Coenzyme Q10 improves endothelial dysfunction in statin-treated type 2 diabetic patients. Diabetes Care 32:810–812. https://doi.org/10.2337/dc08-1736
Hejazi N, Dabbaghmanesh MH, Mazloom Z, Dashtabi A (2015) Effects of vitamin E on fasting and postprandial oxidative stress, inflammatory markers, glucose status, insulin resistance, blood pressure and pulse rate in type-2 diabetic patients: A randomized clinical trial. Galen Med J 4:67–74
Hendra TJ, Britton ME, Roper DR, Wagaine-Twabwe D, Jeremy JY, Dandona P, Haines AP, Yudkin JS (1990) Effects of fish oil supplements in NIDDM subjects. Controlled Study Diabetes Care 13:821–829. https://doi.org/10.2337/diacare.13.8.821
Heshmat R, Tabatabaei-Malazy O, Abbaszadeh-Ahranjani S, Shahbazi S, Khooshehchin G, Bandarian F, Larijani B (2012) Effect of vitamin D on insulin resistance and anthropometric parameters in Type 2 diabetes; a randomized double-blind clinical trial. Daru 20:10. https://doi.org/10.1186/2008-2231-20-10
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558. https://doi.org/10.1002/sim.1186
Higgins JP, Thomas J, Chander J, Cumpson M, Li T, Page MJ, Welch VA (2019) Cochrane handbook for systematic reviews of interventions. John Wiley & Sons, Hoboken
Hodgson JM, Watts GF, Playford DA, Burke V, Croft KD (2002) Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr 56:1137–1142. https://doi.org/10.1038/sj.ejcn.1601464
Hunt AE, Allen KGD, Smith BA (1985) Effect of chromium supplementation on hair chromium concentration and diabetic status. Nutr Res 5:131–140. https://doi.org/10.1016/S0271-5317(85)80028-2
Imanparast F, Javaheri J, Kamankesh F, Rafiei F, Salehi A, Mollaaliakbari Z, Rezaei F, Rahimi A, Abbasi E (2020) The effects of chromium and vitamin D (3) co-supplementation on insulin resistance and tumor necrosis factor-alpha in type 2 diabetes: a randomized placebo-controlled trial. Appl Physiol Nutr Metab 45:471–477. https://doi.org/10.1139/apnm-2019-0113
Jacobo-Cejudo MG, Valdés-Ramos R, Guadarrama-López AL, Pardo-Morales RV, Martínez-Carrillo BE, Harbige LS (2017) Effect of n-3 polyunsaturated fatty acid supplementation on metabolic and inflammatory biomarkers in type 2 diabetes mellitus patients. Nutrients 9:1–11. https://doi.org/10.3390/nu9060573
Jain SK, Kahlon G, Morehead L, Dhawan R, Lieblong B, Stapleton T, Caldito G, Hoeldtke R, Levine SN, Bass PF III (2012) Effect of chromium dinicocysteinate supplementation on circulating levels of insulin, TNF-alpha, oxidative stress, and insulin resistance in type 2 diabetic subjects: randomized, double-blind, placebo-controlled study. Mol Nutr Food Res 56:1333–1341. https://doi.org/10.1002/mnfr.201100719
Jehle S, Lardi A, Felix B, Hulter HN, Stettler C, Krapf R (2014) Effect of large doses of parenteral vitamin D on glycaemic control and calcium/phosphate metabolism in patients with stable type 2 diabetes mellitus: a randomised, placebo-controlled, prospective pilot study. Swiss Med Wkly 144:w13942. https://doi.org/10.4414/smw.2014.13942
Jones NE, Heyland DK (2008) Pharmaconutrition: a new emerging paradigm. Curr Opin Gastroenterol 24:215–222. https://doi.org/10.1097/MOG.0b013e3282f4cdd8
Jorde R, Figenschau Y (2009) Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels. Eur J Nutr 48:349–354. https://doi.org/10.1007/s00394-009-0020-3
Kabir M, Skurnik G, Naour N, Pechtner V, Meugnier E, Rome S, Quignard-Boulangé A, Vidal H, Slama G, Clément K, Guerre-Milo M (2007) Treatment for 2 mo with n-3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am J Clin Nutr 86:1670–1679. https://doi.org/10.1093/ajcn/86.5.1670
Kampmann U, Mosekilde L, Juhl C, Moller N, Christensen B, Rejnmark L, Wamberg L, Orskov L (2014) Effects of 12 weeks high dose vitamin D3 treatment on insulin sensitivity, beta cell function, and metabolic markers in patients with type 2 diabetes and vitamin D insufficiency - a double-blind, randomized, placebo-controlled trial. Metabolism 63:1115–1124. https://doi.org/10.1016/j.metabol.2014.06.008
Keche YN, Yegnanarayan R, Bhat S (2016) Effect of vitamin B12 supplementation on glycemic control in poorly controlled hyperhomocysteinemic type 2 diabetic patients. Bangladesh J Pharmacol 11:50–53. https://doi.org/10.3329/bjp.v11i1.24141
Kim HJ, Park KS, Lee SK, Min KW, Han KA, Kim YK, Ku BJ (2012) Effects of pinitol on glycemic control, insulin resistance and adipocytokine levels in patients with type 2 diabetes mellitus. Ann Nutr Metab 60:1–5. https://doi.org/10.1159/000334834
Kleefstra N, Houweling ST, Jansman FG, Groenier KH, Gans RO, Meyboom-de Jong B, Bakker SJ, Bilo HJ (2006) Chromium treatment has no effect in patients with poorly controlled, insulin-treated type 2 diabetes in an obese Western population: a randomized, double-blind, placebo-controlled trial. Diabetes Care 29:521–525. https://doi.org/10.2337/diacare.29.03.06.dc05-1453
Kleefstra N, Houweling ST, Bakker SJ, Verhoeven S, Gans RO, Meyboom-de Jong B, Bilo HJ (2007) Chromium treatment has no effect in patients with type 2 diabetes in a Western population: a randomized, double-blind, placebo-controlled trial. Diabetes Care 30:1092–1096. https://doi.org/10.2337/dc06-2192
Kolahdouz-Mohammadi R, Hosseinzadeh-Attar MJ, Eshraghian MR, Nakhjavani M, Khorami E, Esteghamati A (2013) The effect of coenzyme Q10 supplementation on metabolic status of type 2 diabetic patients. Minerva Gastroenterol Dietol 59:231–236
Korea Food and Drug Administration Health functional food code (2020) https://www.mfds.go.kr/eng/brd/m_15/view.do?seq=70011&srchFr=&srchTo=&srchWord=&srchTp=&itm_seq_1=0&itm_seq_2=0&multi_itm_seq=0&company_cd=&company_nm=&page=2 Accessed 23 Feb 2022
Król E, Krejpcio Z, Byks H, Bogdański P, Pupek-Musialik D (2011) Effects of chromium brewer’s yeast supplementation on body mass, blood carbohydrates, and lipids and minerals in type 2 diabetic patients. Biol Trace Elem Res 143:726–737. https://doi.org/10.1007/s12011-010-8917-5
Krul-Poel YH, Westra S, ten Boekel E, ter Wee MM, van Schoor NM, van Wijland H, Stam F, Lips PT, Simsek S (2015) Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes (SUNNY trial): a randomized placebo-controlled trial. Diabetes Care 38:1420–1426. https://doi.org/10.2337/dc15-0323
Lai MH (2008) Antioxidant effects and insulin resistance improvement of chromium combined with vitamin C and E supplementation for type 2 diabetes mellitus. J Clin Biochem Nutr 43:191–198. https://doi.org/10.3164/jcbn.2008064
Lesser LI, Ebbeling CB, Goozner M, Wypij D, Ludwig DS (2007) Relationship between funding source and conclusion among nutrition-related scientific articles. PLOS Med 4:e5. https://doi.org/10.1371/journal.pmed.0040005
Lewicki S, Zdanowski R, Krzyżowska M, Lewicka A, Dębski B, Niemcewicz M, Goniewicz M (2014) The role of Chromium III in the organism and its possible use in diabetes and obesity treatment. Ann Agric Environ Med 21:331–335. https://doi.org/10.5604/1232-1966.1108599
Luo J, Rizkalla SW, Vidal H, Oppert JM, Colas C, Boussairi A, Guerre-Millo M, Chapuis AS, Chevalier A, Durand G, Slama G (1998) Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results of a controlled study. Diabetes Care 21:717–724. https://doi.org/10.2337/diacare.21.5.717
Mahmoudabadi MM, Rahbar AR (2014) Effect of EPA and vitamin C on superoxide dismutase, glutathione peroxidase, total antioxidant capacity and malondialdehyde in type 2 diabetic patients. Oman Med J 29:39–45. https://doi.org/10.5001/omj.2014.09
Mansoori A, Sotoudeh G, Djalali M, Eshraghian MR, Keramatipour M, Nasli-Esfahani E, Shidfar F, Alvandi E, Toupchian O, Koohdani F (2015) Effect of DHA-rich fish oil on PPARgamma target genes related to lipid metabolism in type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial. J Clin Lipidol 9:770–777. https://doi.org/10.1016/j.jacl.2015.08.007
Manzella D, Barbieri M, Ragno E, Paolisso G (2001) Chronic administration of pharmacologic doses of vitamin E improves the cardiac autonomic nervous system in patients with type 2 diabetes. Am J Clin Nutr 73:1052–1057. https://doi.org/10.1093/ajcn/73.6.1052
Martin J, Wang ZQ, Zhang XH, Wachtel D, Volaufova J, Matthews DE, Cefalu WT (2006) Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care 29:1826–1832. https://doi.org/10.2337/dc06-0254
Mason SA, Rasmussen B, van Loon LJC, Salmon J, Wadley GD (2019) Ascorbic acid supplementation improves postprandial glycaemic control and blood pressure in individuals with type 2 diabetes: findings of a randomized cross-over trial. Diabetes Obes Metab 21:674–682. https://doi.org/10.1111/dom.13571
Mason SA, Keske MA, Wadley GD (2021) Effects of vitamin C supplementation on glycemic control and cardiovascular risk factors in people with type 2 diabetes: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials. Diabetes Care 44:618–530. https://doi.org/10.2337/dc20-1893
McManus RM, Jumpson J, Finegood DT, Clandinin MT, Ryan EA (1996) A comparison of the effects of n-3 fatty acids from linseed oil and fish oil in well-controlled type II diabetes. Diabetes Care 19:463–467. https://doi.org/10.2337/diacare.19.5.463
McVeigh GE, Brennan GM, Johnston GD, McDermott BJ, McGrath LT, Henry WR, Andrews JW, Hayes JR (1993) Dietary fish oil augments nitric oxide production or release in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 36:33–38. https://doi.org/10.1007/bf00399090
Mehrdadi P, Kolahdouz Mohammadi R, Alipoor E, Eshraghian MR, Esteghamati A, Hosseinzadeh-Attar MJ (2017) The effect of coenzyme Q10 supplementation on circulating levels of novel adipokine adipolin/CTRP12 in overweight and obese patients with type 2 diabetes. Exp Clin Endocrinol Diabetes 125:156–162. https://doi.org/10.1055/s-0042-110570
Memisoğullari R, Taysi S, Bakan E, Capoglu I (2003) Antioxidant status and lipid peroxidation in type II diabetes mellitus. Cell Biochem Funct 21:291–296. https://doi.org/10.1002/cbf.1025
Moazen M, Mazloom Z, Ahmadi A, Dabbaghmanesh MH, Roosta S (2015) Effect of coenzyme Q10 on glycaemic control, oxidative stress and adiponectin in type 2 diabetes. J Pak Med Assoc 65:404–408
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097. https://doi.org/10.1371/journal.pmed.1000097
Moloney F, Yeow TP, Mullen A, Nolan JJ, Roche HM (2004) Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus. Am J Clin Nutr 80:887–895. https://doi.org/10.1093/ajcn/80.4.887
Morgan WA, Raskin P, Rosenstock J (1995) A comparison of fish oil or corn oil supplements in hyperlipidemic subjects with NIDDM. Diabetes Care 18:83–86. https://doi.org/10.2337/diacare.18.1.83
Nasri H, Behradmanesh S, Maghsoudi AR, Ahmadi A, Nasri P, Rafieian-Kopaei M (2014) Efficacy of supplementary vitamin D on improvement of glycemic parameters in patients with type 2 diabetes mellitus; a randomized double blind clinical trial. J Ren Inj Prev 3:31–34. https://doi.org/10.12861/jrip.2014.10
Neil HA, Ceglarek U, Thiery J, Paul S, Farmer A, Holman RR (2010) Impact of atorvastatin and omega-3 ethyl esters 90 on plasma plant sterol concentrations and cholesterol synthesis in type 2 diabetes: a randomised placebo controlled factorial trial. Atherosclerosis 213:512–517. https://doi.org/10.1016/j.atherosclerosis.2010.09.013
Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, Cavan D, Shaw JE, Makaroff LE (2017) IDF Diabetes Atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract 128(suppl c):40–50. https://doi.org/10.1016/j.diabres.2017.03.024
Omidian M, Mahmoudi M, Abshirini M, Eshraghian MR, Javanbakht MH, Zarei M, Hasani H, Djalali M (2019) Effects of vitamin D supplementation on depressive symptoms in type 2 diabetes mellitus patients: randomized placebo-controlled double-blind clinical trial. Diabetes Metab Syndr 13:2375–2380. https://doi.org/10.1016/j.dsx.2019.06.011
Paiva AN, Lima JG, Medeiros AC, Figueiredo HA, Andrade RL, Ururahy MA, Rezende AA, Brandão-Neto J, Almeida Md (2015) Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: a randomized clinical study. J Trace Elem Med Biol 32:66–72. https://doi.org/10.1016/j.jtemb.2015.05.006
Paolisso G, D’Amore A, Galzerano D, Balbi V, Giugliano D, Varricchio M, D’Onofrio F (1993) Daily vitamin E supplements improve metabolic control but not insulin secretion in elderly type II diabetic patients. Diabetes Care 16:1433–1437. https://doi.org/10.2337/diacare.16.11.1433
Paolisso G, Balbi V, Volpe C, Varricchio G, Gambardella A, Saccomanno F, Ammendola S, Varricchio M, D’Onofrio F (1995) Metabolic benefits deriving from chronic vitamin C supplementation in aged non-insulin dependent diabetics. J Am Coll Nutr 14:387–392. https://doi.org/10.1080/07315724.1995.10718526
Paolisso G, Tagliamonte MR, Barbieri M, Zito GA, Gambardella A, Varricchio G, Ragno E, Varricchio M (2000) Chronic vitamin E administration improves brachial reactivity and increases intracellular magnesium concentration in type II diabetic patients. J Clin Endocrinol Metab 85:109–115. https://doi.org/10.1210/jcem.85.1.6258
Parekh D, Sarathi V, Shivane VK, Bandgar TR, Menon PS, Shah NS (2010) Pilot study to evaluate the effect of short-term improvement in vitamin D status on glucose tolerance in patients with type 2 diabetes mellitus. Endocr Pract 16:600–608. https://doi.org/10.4158/ep09300.Or
Parham M, Amini M, Aminorroaya A, Heidarian E (2008) Effect of zinc supplementation on microalbuminuria in patients with type 2 diabetes: a double blind, randomized, placebo-controlled, cross-over trial. Rev Diabet Stud 5:102–109. https://doi.org/10.1900/rds.2008.5.102
Park S, Choi SB (2002) Effects of alpha-tocopherol supplementation and continuous subcutaneous insulin infusion on oxidative stress in Korean patients with type 2 diabetes. Am J Clin Nutr 75:728–733. https://doi.org/10.1093/ajcn/75.4.728
Partida-Hernández G, Arreola F, Fenton B, Cabeza M, Román-Ramos R, Revilla-Monsalve MC (2006) Effect of zinc replacement on lipids and lipoproteins in type 2-diabetic patients. Biomed Pharmacother 60:161–168. https://doi.org/10.1016/j.biopha.2006.02.004
Pérez A, Rojas P, Carrasco F, Basfi-fer K, Pérez-Bravo F, Codoceo J, Inostroza J, Ruz M (2018) Zinc supplementation does not affect glucagon response to intravenous glucose and insulin infusion in patients with well-controlled type 2 diabetes. Biol Trace Elem Res 185:255–261. https://doi.org/10.1007/s12011-018-1249-6
Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI (2003) Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300:1140–1142. https://doi.org/10.1126/science.1082889
Playford DA, Watts GF, Croft KD, Burke V (2003) Combined effect of coenzyme Q10 and fenofibrate on forearm microcirculatory function in type 2 diabetes. Atherosclerosis 168:169–179. https://doi.org/10.1016/s0021-9150(02)00417-3
Pooya Sh, Jalali MD, Jazayery AD, Saedisomeolia A, Eshraghian MR, Toorang F (2010) The efficacy of omega-3 fatty acid supplementation on plasma homocysteine and malondialdehyde levels of type 2 diabetic patients. Nutr Metab Cardiovasc Dis 20:326–331. https://doi.org/10.1016/j.numecd.2009.04.002
Poreba M, Mostowik M, Siniarski A, Golebiowska-Wiatrak R, Malinowski KP, Haberka M, Konduracka E, Nessler J, Undas A, Gajos G (2017) Treatment with high-dose n-3 PUFAs has no effect on platelet function, coagulation, metabolic status or inflammation in patients with atherosclerosis and type 2 diabetes. Cardiovasc Diabetol 16:50. https://doi.org/10.1186/s12933-017-0523-9
Puhakainen I, Ahola I, Yki-Järvinen H (1995) Dietary supplementation with n-3 fatty acids increases gluconeogenesis from glycerol but not hepatic glucose production in patients with non-insulin-dependent diabetes mellitus. Am J Clin Nutr 61:121–126. https://doi.org/10.1093/ajcn/61.1.121
Rabbani N, Alam SS, Riaz S, Larkin JR, Akhtar MW, Shafi T, Thornalley PJ (2009) High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study. Diabetologia 52:208–212. https://doi.org/10.1007/s00125-008-1224-4
Racek J, Trefil L, Rajdl D, Mudrová V, Hunter D, Senft V (2006) Influence of chromium-enriched yeast on blood glucose and insulin variables, blood lipids, and markers of oxidative stress in subjects with type 2 diabetes mellitus. Biol Trace Elem Res 109:215–230. https://doi.org/10.1385/bter:109:3:215
Rafraf M, Bazyun B, Sarabchian MA, Safaeiyan A, Gargari BP (2016) Vitamin E improves serum paraoxonase-1 activity and some metabolic factors in patients with type 2 diabetes: no effects on nitrite/nitrate levels. J Am Coll Nutr 35:521–528. https://doi.org/10.1080/07315724.2015.1116896
Randhawa FA, Mustafa S, Khan DM, Hamid S (2017) Effect of vitamin D supplementation on reduction in levels of HbA1 in patients recently diagnosed with type 2 diabetes mellitus having asymptomatic vitamin D deficiency. Pak J Med Sci 33:881–885. https://doi.org/10.12669/pjms.334.12288
Rashidi H, Ghaderian SB, Shirinpour Z, Yazdanpanah L, Kaykhaei MA, Aleali AM, Latifi SM, Bazdar M (2016) The effect of vitamin D supplementation on insulin resistance and glycemic control in patients with type 2 diabetes. Int J Pharm Technol 8:11634–11642
Reaven PD, Herold DA, Barnett J, Edelman S (1995) Effects of vitamin E on susceptibility of low-density lipoprotein and low-density lipoprotein subfractions to oxidation and on protein glycation in NIDDM. Diabetes Care 18:807–816. https://doi.org/10.2337/diacare.18.6.807
Rekha NMR, Sattigeri BM (2013) Comparison of efficacy and tolerability of vitamin C as add on therapy to the oral hypoglycaemic agent in newly diagnosed type 2 diabetes mellitus. Int J Drug Dev Res 5:187–194
Rivellese AA, Maffettone A, Iovine C, Di Marino L, Annuzzi G, Mancini M, Riccardi G (1996) Long-term effects of fish oil on insulin resistance and plasma lipoproteins in NIDDM patients with hypertriglyceridemia. Diabetes Care 19:1207–1213. https://doi.org/10.2337/diacare.19.11.1207
Rodrigues MRK, Lima SAM, Mazeto GMFDS, Calderon IMP, Magalhães CG, Ferraz GAR, Molina AC, Costa RAA, Nogueira VDSN, Rudge MVC (2019) Efficacy of vitamin D supplementation in gestational diabetes mellitus: systematic review and meta-analysis of randomized trials. PLoS ONE 14:e0213006. https://doi.org/10.1371/journal.pone.0213006
Ryu OH, Lee S, Yu J, Choi MG, Yoo HJ, Mantero F (2014) A prospective randomized controlled trial of the effects of vitamin D supplementation on long-term glycemic control in type 2 diabetes mellitus of Korea. Endocr J 61:167–176. https://doi.org/10.1507/endocrj.ej13-0356
Sadiya A, Ahmed SM, Carlsson M, Tesfa Y, George M, Ali SH, Siddieg HH, Abusnana S (2015) Vitamin D supplementation in obese type 2 diabetes subjects in Ajman, UAE: a randomized controlled double-blinded clinical trial. Eur J Clin Nutr 69:707–711. https://doi.org/10.1038/ejcn.2014.251
Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K, Shaw JE, Bright D, Williams R (2019) Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract 157:107843. https://doi.org/10.1016/j.diabres.2019.107843
Safarpour P, Daneshi-Maskooni M, Vafa M, Nourbakhsh M, Janani L, Maddah M, Amiri FS, Mohammadi F, Sadeghi H (2020) Vitamin D supplementation improves SIRT1, Irisin, and glucose indices in overweight or obese type 2 diabetic patients: a double-blind randomized placebo-controlled clinical trial. BMC Fam Pract 21:26. https://doi.org/10.1186/s12875-020-1096-3
Saiyed ZM, Lugo JP (2016) Impact of chromium dinicocysteinate supplementation on inflammation, oxidative stress, and insulin resistance in type 2 diabetic subjects: an exploratory analysis of a randomized, double-blind, placebo-controlled study. Food Nutr Res 60:31762. https://doi.org/10.3402/fnr.v60.31762
Sanguanwong S, Tangvarasittichai O, Sengsuk C, Tangvarasittichai S (2016) Oral supplementation of vitamin C reduced lipid peroxidation and insulin resistance in patients with type 2 diabetes mellitus. Int J Toxicol Pharmacol Res 8:114–119
Sarbolouki S, Javanbakht MH, Derakhshanian H, Hosseinzadeh P, Zareei M, Hashemi SB, Dorosty AR, Eshraghian MR, Djalali M (2013) Eicosapentaenoic acid improves insulin sensitivity and blood sugar in overweight type 2 diabetes mellitus patients: a double-blind randomised clinical trial. Singapore Med J 54:387–390. https://doi.org/10.11622/smedj.2013139
Schectman G, Kaul S, Kissebah AH (1988) Effect of fish oil concentrate on lipoprotein composition in NIDDM. Diabetes 37:1567–1573. https://doi.org/10.2337/diab.37.11.1567
Seet RC, Lee CY, Lim EC, Quek AM, Huang H, Huang SH, Looi WF, Long LH, Halliwell B (2011) Oral zinc supplementation does not improve oxidative stress or vascular function in patients with type 2 diabetes with normal zinc levels. Atherosclerosis 219:231–239. https://doi.org/10.1016/j.atherosclerosis.2011.07.097
Seida JC, Mitri J, Colmers IN, Majumdar SR, Davidson MB, Edwards AL, Hanley DA, Pittas AG, Tjosvold L, Johnson JA (2014) Clinical review: effect of vitamin D3 supplementation on improving glucose homeostasis and preventing diabetes: a systematic review and meta-analysis. J Clin Endocrinol Metab 99:3551–3560. https://doi.org/10.1210/jc.2014-2136
Sharma S, Agrawal RP, Choudhary M, Jain S, Goyal S, Agarwal V (2011) Beneficial effect of chromium supplementation on glucose, HbA1c and lipid variables in individuals with newly onset type-2 diabetes. J Trace Elem Med Biol 25:149–153. https://doi.org/10.1016/j.jtemb.2011.03.003
Shidfar F, Keshavarz A, Hosseyni S, Ameri A, Yarahmadi S (2008) Effects of omega-3 fatty acid supplements on serum lipids, apolipoproteins and malondialdehyde in type 2 diabetes patients. East Mediterr Health J 14:305–313
Soliman GZA, Bahagt NM (2012) Effect of vitamin C and/or vitamin E on oxidative stress and lipid profile in diabetic rats. Res J Pharm Biol Chem Sci 3:639–652
Sosale B, Sosale AR, Chandrashekara S, Panchagnula R, Dey S, Prasannakumar KM (2018) Effect of vitamin D supplementation on reduction of cardiometabolic risk in patients with type 2 diabetes mellitus and dyslipidemia. Int J Diabetes Dev Ctries 38:221–227. https://link.springer.com/content/pdf/10.1007/s13410-017-0584-z
Stonehouse W, Brinkworth GD, Thompson CH, Abeywardena MY (2016) Short term effects of palm-tocotrienol and palm-carotenes on vascular function and cardiovascular disease risk: a randomised controlled trial. Atherosclerosis 254:205–214. https://doi.org/10.1016/j.atherosclerosis.2016.10.027
Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321:405–412. https://doi.org/10.1136/bmj.321.7258.405
Sugden JA, Davies JI, Witham MD, Morris AD, Struthers AD (2008) Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels. Diabet Med 25:320–325. https://doi.org/10.1111/j.1464-5491.2007.02360.x
Suksomboon N, Poolsup N, Yuwanakorn A (2014) Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes. J Clin Pharm Ther 39:292–306. https://doi.org/10.1111/jcpt.12147
Talab AT, Abdollahzad H, Nachvak SM, Pasdar Y, Eghtesadi S, Izadi A, Aghdashi MA, Mohammad Hossseini Azar MR, Moradi S, Mehaki B, Moradi S (2020) Effects of chromium picolinate supplementation on cardiometabolic biomarkers in patients with type 2 diabetes mellitus: a randomized clinical trial. Clin Nutr Res 9:97–106. https://doi.org/10.7762/cnr.2020.9.2.97
Tütüncü NB, Bayraktar M, Varli K (1998) Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes: a preliminary study. Diabetes Care 21:1915–1918. https://doi.org/10.2337/diacare.21.11.1915
Udupa AS, Nahar PS, Shah SH, Kshirsagar MJ, Ghongane BB (2012) Study of comparative effects of antioxidants on insulin sensitivity in type 2 diabetes mellitus. J Clin Diagn Res 6:1469–1473. https://doi.org/10.7860/jcdr/2012/4464.2535
UK Prospective Diabetes Study Group (1998) Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 352:854–865. https://pubmed.ncbi.nlm.nih.gov/9742977/
Upreti V, Maitri V, Dhull P, Handa A, Prakash MS, Behl A (2018) Effect of oral vitamin D supplementation on glycemic control in patients with type 2 diabetes mellitus with coexisting hypovitaminosis D: a parallel group placebo controlled randomized controlled pilot study. Diabetes Metab Syndr 12:509–512. https://doi.org/10.1016/j.dsx.2018.03.008
Uusitupa MI, Kumpulainen JT, Voutilainen E, Hersio K, Sarlund H, Pyörälä KP, Koivistoinen PE, Lehto JT (1983) Effect of inorganic chromium supplementation on glucose tolerance, insulin response, and serum lipids in noninsulin-dependent diabetics. Am J Clin Nutr 38:404–410. https://doi.org/10.1093/ajcn/38.3.404
Vafa M, Haghighat N, Moslehi N, Eghtesadi S, Heydari I (2015) Effect of tocotrienols enriched canola oil on glycemic control and oxidative status in patients with type 2 diabetes mellitus: a randomized double-blind placebo-controlled clinical trial. J Res Med Sci 20:540–547. https://doi.org/10.4103/1735-1995.165945
Vrtovec M, Vrtovec B, Briski A, Kocijancic A, Anderson RA, Radovancevic B (2005) Chromium supplementation shortens QTc interval duration in patients with type 2 diabetes mellitus. Am Heart J 149:632–636. https://doi.org/10.1016/j.ahj.2004.07.021
Wang ZQ, Cefalu WT (2010) Current concepts about chromium supplementation in type 2 diabetes and insulin resistance. Curr Diabetes Rep 10:145–151. https://doi.org/10.1007/s11892-010-0097-3
Wang F, Wang Y, Zhu Y, Liu X, Xia H, Yang X, Sun G (2017) Treatment for 6 months with fish oil-derived n-3 polyunsaturated fatty acids has neutral effects on glycemic control but improves dyslipidemia in type 2 diabetic patients with abdominal obesity: a randomized, double-blind, placebo-controlled trial. Eur J Nutr 56:2415–2422. https://doi.org/10.1007/s00394-016-1352-4
Ward NC, Wu JH, Clarke MW, Puddey IB, Burke V, Croft KD, Hodgson JM (2007) The effect of vitamin E on blood pressure in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. J Hypertens 25:227–234. https://doi.org/10.1097/01.hjh.0000254373.96111.43
Westerveld HT, de Graaf JC, van Breugel HH, Akkerman JW, Sixma JJ, Erkelens DW, Banga JD (1993) Effects of low-dose EPA-E on glycemic control, lipid profile, lipoprotein(a), platelet aggregation, viscosity, and platelet and vessel wall interaction in NIDDM. Diabetes Care 16:683–688. https://doi.org/10.2337/diacare.16.5.683
Weykamp C (2013) HbA1c: a review of analytical and clnical aspects. Ann Lab Med 33:393–400. https://doi.org/10.3343/alm.2013.33.6.393
Winterbone MS, Sampson MJ, Saha S, Hughes JC, Hughes DA (2007) Pro-oxidant effect of alpha-tocopherol in patients with type 2 diabetes after an oral glucose tolerance test: a randomised controlled trial. Cardiovasc Diabetol 6:8. https://doi.org/10.1186/1475-2840-6-8
Witham MD, Dove FJ, Dryburgh M, Sugden JA, Morris AD, Struthers AD (2010) The effect of different doses of vitamin D(3) on markers of vascular health in patients with type 2 diabetes: a randomised controlled trial. Diabetologia 53:2112–2119. https://doi.org/10.1007/s00125-010-1838-1
Wong CY, Yiu KH, Li SW, Lee S, Tam S, Lau CP, Tse HF (2010) Fish-oil supplement has neutral effects on vascular and metabolic function but improves renal function in patients with type 2 diabetes mellitus. Diabet Med 27:54–60. https://doi.org/10.1111/j.1464-5491.2009.02869.x
Yousefi Rad EY, Djalali M, Koohdani F, Saboor-Yaraghi AA, Eshraghian MR, Javanbakht MH, Saboori S, Zarei M, Hosseinzadeh-Attar MJ (2014) The effects of vitamin D supplementation on glucose control and insulin resistance in patients with diabetes type 2: a randomized clinical trial study. Iran J Public Health 43:1651–1656. https://doaj.org/article/92daf676694a48bf8a4f0096b1a668a6
Zahedi H, Eghtesadi S, Seifirad S, Rezaee N, Shidfar F, Heydari I, Golestan B, Jazayeri S (2014) Effects of CoQ10 supplementation on lipid profiles and glycemic control in patients with type 2 diabetes: a randomized, double blind, placebo-controlled trial. J Diabetes Metab Disord 13:81. https://doi.org/10.1186/s40200-014-0081-6
Zhang SY, Yang KL, Zeng LT, Wu XH, Huang HY (2018) Effectiveness of coenzyme Q10 supplementation for type 2 diabetes mellitus: a systematic review and meta-analysis. Int J Endocrinol 2018:6484839. https://doi.org/10.1155/2018/6484839
Zhao L, Sun T, Wang L (2017) Chitosan oligosaccharide improves the therapeutic efficacy of sitagliptin for the therapy of Chinese elderly patients with type 2 diabetes mellitus. Ther Clin Risk Manag 13:739–750. https://doi.org/10.2147/tcrm.S134039
Zhao F, Pan D, Wang N, Xia H, Zhang H, Wang S, Sun G (2022) Effect of chromium supplementation on blood glucose and lipid levels in patients with Type 2 diabetes mellitus: a systematic review and meta-analysis. Bio Trace Elem Res 200(2):516–525. https://doi.org/10.1007/s12011-021-02693-3
Zheng JS, Lin M, Fang L, Yu Y, Yuan L, Jin Y, Feng J, Wang L, Yang H, Chen W, Li D, Tang J, Cai W, Shi M, Li Z, Wang F, Li D (2016) Effects of n-3 fatty acid supplements on glycemic traits in Chinese type 2 diabetic patients: a double-blind randomized controlled trial. Mol Nutr Food Res 60:2176–2184. https://doi.org/10.1002/mnfr.201600230
Ziegler D, Schatz H, Conrad F, Gries FA, Ulrich H, Reichel G (1997) Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. a 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie Diabetes Care 20:369–373. https://doi.org/10.2337/diacare.20.3.369
Acknowledgements
This study was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (Grant Numbers 2018R1D1A1B07046564 and 2021R1A6A1A03044296) and by NRF grant funded by the Korea government (Ministry of Science and ICT, MICT) (NRF-2021R1F1A1062044). The funders had no role in study design, data collection, data analysis, or decision to publish and preparation of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All authors declare that there are no conflicts of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Registration number: PROSPERO__CRD42018115229.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Kim, Y., Oh, Y.K., Lee, J. et al. Could nutrient supplements provide additional glycemic control in diabetes management? A systematic review and meta-analysis of randomized controlled trials of as an add-on nutritional supplementation therapy. Arch. Pharm. Res. 45, 185–204 (2022). https://doi.org/10.1007/s12272-022-01374-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-022-01374-6