Table 2.

The outcome of the interventional clinical trials focused on the effect of vitamin D supplementation on the metabolic parameters related to lipid metabolism. ↑—increase, ↓—decrease and ↓↑—no statistical effect.

Reference	Target Population	Study Design	Results on Studied Parameters
Sharifi et al. 2016 [238]	NAFLD Intervention group (n = 27: 13 men (age: 39 [31, 48.5]) and 14 women (age: 41 [35, 46.7])) received 50,000 IU of calcitriol every 14 days for four months Placebo group (n = 26: 13 men (age: 35 [32, 55]) and 13 women )age: 47 [43.5, 52.5]))	Double-blind, randomized-controlled clinical trial	↓TC, ↓LDL-C (in women) ↑TC, ↓↑LDL-C (in men)
Lorvand Amiri et al. 2017 [239]	NAFLD Intervention groups: - received 1000 IU of calcitriol daily for 12 weeks (n = 37: 22 men and 15 women; age: 39.8 ± 11) - received 500-mg calcium carbonate + 1000 IU of calcitriol daily for 12 weeks (n = 37: 23 men and 14 women; age: 38 ± 10.1) Placebo group (n = 36: 23 men and 13 women; age: 44 ± 10.8)	Randomized, placebo-controlled, double-blind clinical trial	↓WT, ↓BMI, ↓fat mass, ↓FPG, ↓insulin, ↓HOMA-IR, ↓TG, ↑HDL-C, ↓ALT
Foroughi et al. 2014 [240]	NAFLD Intervention group (n = 30) received 50,000 IU of vitamin D weekly over 10 weeks Placebo group (n = 30) 60 patients included in study (n = 60: 29 men and 31 women; age; 48.5)	Randomized double-blind placebo-controlled clinical trial	↓TG, ↓CRP, ↑Ca2+
Khosravi et al. 2018 [241]	Overweight and obese women Intervention group (n = 26 women; age: 29.1 ± 9.6) received vitamin D with doses 50,000 IU/w for 6 weeks Placebo group (n = 27 women; age: 26.9 ± 9.1)	Double-blind placebo-controlled clinical trial	↓WT, ↓WC, ↓BMI ↓↑TC, ↓↑TG, ↓↑LDL-C, ↓↑HDL-C, ↓↑FBS, ↓↑ insulin, ↓↑HOMA-IR, ↓↑WHR
Wamberg et al. 2013 [242]	Obese adults Intervention group (n = 26: 18 men and 18 women; age: 39.5 ± 8.0) received 7000 IU of cholecalciferol daily for 26 weeks Placebo group (n = 26: 7 men and 19 women; age: 41.2 ± 6.8)	Randomized double-blind placebo-controlled clinical trial	↓↑body fat, ↓↑SAT, ↓↑VAT, ↓↑IHL, ↓↑IMCL, ↓↑HOMA-IR, ↓↑blood pressure, ↓↑HDL-C, ↓↑TG, ↓↑TC, ↓↑hsCRP
Salehpour et al. 2012 [243]	Overweight and obese women Intervention group (n = 39 woman; age: 38 ± 7) received 1000 IU per day of cholecalciferol for 12 weeks Placebo group (n = 38 woman; age: 38 ± 8)	Double-blind, randomized, placebo-ontrolled, parallel group trial	↓ fat mass, ↓↑WT, ↓↑WC
Zittermann et al. 2009 [244]	Overweight subjects Intervention group (n = 82: 31 men and 51 women; age: 47.4 ± 10.3) received 3320 IU per day of vitamin D for 12 months Placebo group (n = 83: 23 men and 60 women; age: 48.8 ± 10.1)	Double-blind placebo-controlled clinical trial	↓PTH, ↓TG, ↓TNF-α, ↑LDL-C
Sneve et al. 2008 [245]	Overweight and obese subjects Intervention groups: - (n = 116: 57 men and 96 women; age: 46.4 ± 11.3) received calcium 500 mg/day + 40,000 IU of cholecalciferol/week for 12 months - (n = 106: 51 men and 92 women; age: 47.6 ± 11.9) received calcium 500 mg/day + 20,000 IU of cholecalciferol/week for 12 months Placebo group (n = 112: 51 men and 98 women; age: 48.9 ± 11.0) received calcium 500 mg/day + placebo for 12 months	Randomized double-blind, placebo-controlled clinical trial	↓↑WHR, ↓↑ fat, ↓↑Ca, ↓PTH
Major et al. 2007 [246]	Overweight or obese women Intervention group (n = 30 women; age: 43.6 ± 5.0) received 2 tablets/d of a calcium + vitamin D supplement (600-mg elemental calcium and 200 IU of vitamin D/tablet) for 15 weeks Placebo group (n = 33 women; age: 41.6 ± 6.1)	Double-blind, clinical placebo-controlled trial	↓LDL-C, ↓LDL:HDL ratio, ↓↑ HDL-C, ↓TG, ↓TC, ↓total HDL
Farag et al. 2019 [247]	Metabolic syndrome patients Intervention groups: - (n = 24: 8 men and 16 women; age:40.54 ± 5.94) received 2000 IU of vitamin D per day for 12 weeks - (n = 21: 7 men and 14 women; age: 40.42 ± 5.89) received 2000 IU of vitamin D per day plus 30 min of endurance physical activity for 12 weeks Placebo group (n = 25: 13 men and 12 women; age: 42.6 ± 5.62)	Parallel randomized placebo-controlled trial	↓TC, ↓LDL-C (in vitamin D + physical activity group) ↓↑TG, ↓↑HDL-C (in all three groups)
Mikariou et al. 2017 [248]	Metabolic syndrome patients Intervention group (n = 25: 15 men and 10 women; age: 52.0 ± 9.0) received 2000 IU of vitamin D/day for 3 months Placebo group (n = 25: 11 men and 14 women; age: 51.0 ± 12.0)	Prospective, randomized, open-label, blinded placebo-controlled end-point trial	↓↑TG, ↓↑HDL-C, ↓↑LDL-C, ↓↑FTG, ↓↑ HbA1c, ↓↑HOMA-IR, ↓↑DBP, ↓SBP
Mikariou et al. 2019 [249]	Metabolic syndrome patients Intervention group (n = 25: 15 men and 10 women; age: 52.0 ± 9.0)) received 2000 IU of vitamin D /day for 3 months Placebo group (n = 25: 11 men and 14 women; age: 51.0 ± 12.0)	Prospective, randomized, open-label, blinded placebo-controlled end-point trial	↓↑sdLDL-C, ↓↑LDL size, ↓↑LpPLA2 activity, ↓↑leptin, ↓↑ adiponectin, ↓↑leptin:adiponectin ratio
Salekzamani et al. 2016 [250]	Metabolic syndrome patients Intervention group (n = 35) received 50,000 IU cholecalciferol/week for 16 weeks Placebo group (n = 36) 71 patients included into study (n = 71: 35 men and 36 women; age; 40.49 ± 5.04)	Randomized placebo-controlled, double-blind parallel trial	↓TG, ↓↑FBG, ↓↑HOMA-IR, ↓↑LDL-C, ↓↑HDL-C, ↓↑TC, ↓↑WC, ↓↑BMI, ↓↑HC, ↓↑DBP, ↓↑SBP, ↓↑FP
Wongwiwatthana- nukit et al. 2013 [251]	Metabolic syndrome patients Intervention group - (n = 30: 16 men and 14 women; age: 62.29 ± 10.63) received 40,000 IU of vitamin D2 (ergocalciferol)/week for 8 weeks - (n = 30: 15 men and 15 women; age: 63.61 ± 13.25) received 20,000 IU of vitamin D2 (ergocalciferol)/week for 8 weeks Placebo group (n = 30: 15 men and 15 women; age: 65.07 ± 11.31)	Prospective, randomized, double-blind, Double-dummy, placebo-controlled parallel trial	↓↑FPG, ↓↑FPI, ↓↑HOMA-IR, ↓↑TC, ↓↑TG, ↓↑HDL-C, ↓↑LDL-C
Yin et al. 2016 [252]	Metabolic syndrome patients Intervention group (n = 61) received 700 IU of cholecalciferol/day for 12 months Placebo group (n = 62)	Randomized placebo-controlled intervention trial	↓↑BMI, ↓↑WC, ↓↑FPG, ↓↑FPI, ↓↑HOMA-IR, ↓↑TG, ↓↑HDL-C, ↓↑LDL-C, ↓↑SBP, ↓↑DBP
Barzegari et al. 2019 [253]	Diabetic nephropathy patients Intervention group (n = 25; age: 39.7 ± 7.3) received 50,000 IU of cholecalciferol/week for 8 weeks/Placebo group (n = 25; age: 43.7 ± 6.1)	Paralleled, randomized, double-blinded, placebo-controlled clinical trial	↓TG, ↓LDL, ↓TC, ↓↑HDL ↑↓ oxidative/antioxidative markers
El Hajj et al. 2018 [254]	Elderly subjects (nondiabetic with vitamin D deficiency) Intervention group (n = 60: 33 men and 27 women; age: 73.0 ± 1.95) received 30,000 IU of cholecalciferol/week for 6 months Placebo group (n = 55: 26 men and 29 women; age: 73.5 ± 2.1)	Randomized placebo-controlled trial	↓HOMA-IR, ↓FBG, ↓TC, ↓LDL-C, ↓BMI, ↓↑HDL-C
Tabesh et al. 2014 [255]	Nonsmoker individuals with T2DM and vitamin D insufficiency Intervention group - (n = 29: 15 men and 14 women; age: 50.2 ± 6.6)) received 50,000 IU of calcitriol/week for 8 weeks - (n = 29: 14 men and 15 women; age: 53.7 ± 5.7) received calcium 1000 mg/day for 8 weeks - (n = 30: 15 men and 15 women; age: 49.8 ± 6.1) received 50,000 IU of calcitriol/week + 1000 mg/day calcium for 8 weeks Placebo group (n = 30: 14 men and 16 women; age: 51.0 ± 6.1)	Randomized placebo-controlled clinical trial	↓serum insulin, ↓HbA1c, ↓HOMA-IR, ↓LDL-C, ↓TC/HDL-C, ↑HDL-C
Wenclewska et al. 2019 [232]	Elderly subjects with metabolic disorders Intervention group (n = 48: 18 subjects with T2DM and 30 controls; 14 men and 34 women; age: 63.43 ± 1.57) received 2000 IU of cholecalciferol/day for 3 months Placebo group (n = 44: 14 subjects with T2DM and 30 controls; 19 men and 25 women; age: 69.78 ± 2.1)	Randomized placebo-controlled clinical trial	↑HDL-C, ↓HOMA-IR, ↓TG:HDL-C ratio (in vitamin D-supplemented group) ↓HbA1c (in T2DM supplemented with vitamin D group)
Upreti et al. 2018 [256]	T2DM patients with hypovitaminosis D Intervention group (n = 30: 15 men and 15 women; age: 48.3 ± 9.8) received 60,000 IU of cholecalciferol/week for first 6 weeks and then once every 4 weeks until completion of the study (6 months) Placebo group (n = 30: 23 men and 7 women; age: 49.9 ± 6.9)	Randomized, parallel group, placebo-controlled trial	↓FPG, ↓PPPG, ↓HbA1c, ↓SBP, ↓DBP, ↓TC, ↓LDL-C, ↓↑TG, ↑↓HDL-C
Tepper et al. 2016 [257]	Healthy men without diabetes with vitamin D deficiency/insufficiency Intervention group (n = 78) received 100,000 IU of calcitriol/bimonthly for 12 months Placebo group (n = 52) 130 men included into study (n = 130; age; 47.52 ± 11.84)	Double-blind randomized-controlled trial	↓↑BMI, ↓↑glucose, ↓↑insulin, ↓↑hsCRP, ↓↑HOMA-IR, ↓↑HOMA-β

Abbreviations: TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; PPPG, post-prandial plasma glucose; DBP, diastolic blood pressure; SBP, systolic blood pressure; BMI, body mass index; FPI, fasting plasma insulin; FPG, fasting plasma glucose; hs-CRP, high-sensitive C-Reactive Protein; TG, triglycerides; HOMA-IR, Homeostatic Model Assessment for Insulin Resistance; HbA1c, glycated hemoglobin; PTH, parathyroid hormone; FBG, fasting blood glucose; HOMA-β, Homeostatic Model Assessment of β-cells Function; TNF-α, tumor necrosis factor α; WT, weight; SAT, subcutaneous; WAT, visceral adipose tissue; IHL, intrahepatic lipids; IMCL, intramyocellular lipids; ALT, alanine aminotransferase; WC, waist circumference; FBS, fasting blood sugar; WHR, waist-to-hip ratio; FTG, fasting triglycerides; sd-LDL-C, small dense LDL-C; LpPLA2, lipoprotein-associated phospholipase A2; HC, hip circumference; FP, fat body percent. ↓—decrease, ↑—increase, and ↓↑—no statistical effect.