Table 1.
Synthesis of meta-analyses and systematic reviews on the effectiveness of various dosages of vitamin D administration in pathologic conditions analyzed.
| Author/Year | Design | Duration | Participants (I/C) |
Dose of Vitamin D |
Results |
|---|---|---|---|---|---|
| VITAMIN D AND INSULIN RESISTANCE (IR) | |||||
| Asbaghi et al., 2019 [46] |
MT (12 RCTs) | From 6 to 312 weeks | 8946 healthy subjects or patients with overweight/obesity, IFG, pre-diabetes, GDM, T2DM, PCOS, HIV infection (4395/4551) |
From 200 IU/day Vitamin D3 to 50,000 IU/week Vitamin D3 (with supplementation dose of calcium that ranged from 500 mg/day to 1000 mg/day) | Reduce effects on FBG, circulating levels of insulin, and HOMA-IR |
| Sindhughosa et al., 2022 [41] | MT (7 RCTs) | From 10 to 52 weeks | 735 patients with NAFLD (423/312) | From 1000 IU/day Vitamin D3 to 50,000 IU/week Vitamin D3 | Improvement in IR (marked by a decrease in HOMA-IR), decrease in ALT levels |
| Pienkowska et al., 2023 [29] |
SR (8 RCTs) | From 12 to 260 weeks | From 66 to 2423 patients with prediabetes |
From 1000 IU/day Vitamin D3 to 88,000 IU/week Vitamin D3 | Only one trial showed improvements in FBG and HOMA-IR |
| VITAMIN D AND TYPE 2 DIABETES MELLITUS (T2DM) | |||||
| Pittas et al., 2007 [61] |
MT (13 case–control studies; 15 cross-sectional studies; 12 RCTs) | N/A | Patients with T2DM or prediabetes |
2000 IU/day Vitamin D3 or Vitamin D3 700 IU/day with supplementation dose of 500 mg/day calcium citrate |
Vitamin D and calcium insufficiency may negatively influence glycemia, whereas combined supplementation with both nutrients may be beneficial in optimizing glucose metabolism |
| Krul-Poel et al., 2017 [86] |
MT (23 RCTs) | From 4 to 52 weeks | 1797 patients with T2DM: for the effect on HbA1c 1475 patients (755/720), for the effect on FBG 1180 patients (608/572) |
From 1000 IU/day Vitamin D3 to 45,000 IU/week Vitamina D3 or 11,200 IU/day Vitamin D3 for 2 weeks followed by 5600 IU/day for 10 weeks or from 100,000 to 300,000 IU Vitamin D3 single dose | Significant effect on FBG in a subgroup of studies (n = 4); no significant effect in change in HbA1c |
| Mirhosseini et al., 2018 [57] | MT (28 RCTs) | From 8 to 260 weeks | 3848 healthy subjects or patients with prediabetes and/or overweight or obesity, NAFLD, arterial hypertension, cervical intraepithelial neoplasia, premenopausal and postmenopausal women | From 420 IU/day to 88,880 IU/week Vitamin D3 | Significant reduction in HbA1c, FBG, and HOMA-IR |
| Hu et al., 2019 [66] |
MT (19 RCTs) | From 4 to 24 weeks | 1374 patients with T2DM (747/627) |
Up to 50,000 UI/weekly Vitamin D3 or 300,000 UI single injection Vitamin D3 | Significant reduction in HbA1c, IR (marked by a decrease in HOMA-IR) and insulin levels in the short-term vitamin D supplementation group |
| VITAMIN D AND TYPE 1 DIABETES MELLITUS (T1DM) | |||||
| Gregoriou et al., 2017 [138] |
MT (7 RCTs) | From 4 to 52 weeks | 287 patients with T1DM |
Calcitriol 0.25 μg per day or on alternate days plus insulin Alphacalcidole 0.5 μg daily plus insulin Cholecalciferol 2000 IU per day plus insulin for 18 mo Cholecalciferol 70 IU/kg body weight/day plus insulin |
Vitamin D supplementation in the form of alphacalcidole and chole- calciferol appears to be beneficial in daily insulin dose (DID), fasting C- peptide (FCP), stimulated C-peptide (SCP), and HbA1c. |
| Najjar et al., 2021 [140] |
MT (10 studies: 3 cohort; 5 case–control; 2 matched case–control) |
N/A | 39,884 patients with T1DM (16,370/23,514) |
N/A | No large effect of a genetically determined reduction in 25(OH)D concentrations by selected polymorphisms on T1D risk |
| Hou et al., 2021 [129] |
MT (16 studies: 12 case–control studies; 1 cross-sectional case–control study; 2 nested case–control study; 1 case–cohort study) |
N/A | 10,605 patients with T1DM (3913/6692) |
N/A | Results demonstrated a significant inverse association between the 25(OH)D concentration in circulation and the risk of T1DM |
| Nascimento et al., 2022 [139] | SR (10 studies) | From 6 to 52 weeks | Children and adolescents (0–19 years) with T1DM | Cholecalciferol, with dosages ranging from 1000 to 160,000 IU. Just one study used vitamin D in the form of alfacalcidol at a dosage of 0.25 to 0.5 μg/day | This study did not provide evidence to support the effect of vitamin D supplementation on glycemic control to aid in the treatment of T1DM |
| Yu et al., 2022 [137] |
SR (13 studies: 9 RCTs; 2 open-label case–control; 1 open label; 1 cohort) |
From 4 to 12 weeks | 527 patients with T1DM |
The following therapeutic regimens were used: 1.25 D 0.25 μg 2nd daily; 25 D 2000 IU daily; 25 D to achieve serum 25 D > 125 nmol/L; Alfacalcidol 0.25 μg bd 25 D; 60,000 IU monthly; Ergocalciferol (D2) 2 m of 50,000 IU/w; 25 D 2000 IU/d; 25D. 3000 IU/d; Calciferol 2000 IU/d + etanercept + GAD-alum |
The maintenance of optimal circulating 25 D levels may reduce the risk of T1D and that may have potential for benefits in delaying the development of absolute or near-absolute C-peptide deficiency |
| VITAMIN D AND GESTATIONAL DIABETES MELLITUS (GDM) | |||||
| Akbari et al., 2017 [167] |
MT (6 RCTs) | From 6 to 12 weeks | 371 pregnant women with GDM (187/184) | 50,000 IU vitamin D3 2 times during the study or 50,000 IU vitamin D3 once every 2 weeks for 2 months, for a total of 200,000 IU vitamin D3 or 50,000 U vitamin D3 pearl twice during the study + 1000 mg calcium per day or 1000 IU vitamin D3 and 1000 mg evening primrose oil (EPO) or one intramuscular injection of 300,000 IU of vitamin D3 or a total of 700,000 IU vitamin D3 during pregnancy | This meta-analysis has demonstrated that vitamin D supplementation may lead to an improvement in HOMA-IR, QUICKI, and LDL-cholesterol levels but did not affect FPG, insulin, HbA1c, triglycerides, total-, and HDL-cholesterol levels; however, vitamin D supplementation increased HOMA-B. |
| Jahanjoo et al., 2018 [169] |
MT (5 RCTs) | From 6 to 16 weeks | 310 women with GDM | 50,000 IU vitamin D3 2 times during the study or 200,000 IU vitamin D3 for each of the first 2 days, and then 50,000 IU per week thereafter, up to 700,000 IU in total. Those at week 28 of gestation or later were asked to take 100,000 IU weekly or 50,000 IU of vitamin D3 once every 2 weeks | This study showed that supplementation of GDM women with vitamin D may lead to an improvement in FPG, TC, LDL, HDL, and hs-CRP serum levels, as well as in newborns’ hyperbilirubinemia |
| Rodrigues et al., 2019 [170] |
MT (6 RCT studies) | From 6 to 24 weeks and a study until delivery | 456 pregnant women with GDM diagnosed in the second or third trimester of pregnancy |
50,000 IU of vitamin D3 every 2 weeks or 1000 UI daily |
Improves adverse maternal and neonatal outcomes related to GDM |
| Milajerdi et al., 2021 [145] |
MT (29 studies: 18 cohort; 9 nested case–control; 1 prospective cross-sectional; 1 retrospective cohort) |
N/A | 42,668 patients with GDM or not |
Blood vitamin D levels | The lowest risk of GDM was found among those with serum vitamin D levels of 40 and 90 nmol/L |
| Wang et al., 2021 [44] |
MT (19 RCTs; of these, 13 concerned GDM) | From 6 to 12 weeks | 1198 patients with GDM |
From 50,000 IU of vitamin D3 2 times/day to 1200 IU daily |
The results showed that vitamin D supplementation during pregnancy could significantly reduce maternal cesarean section rate, maternal hospitalization rate, and postpartum hemorrhage in women with GDM |
| Chatzakis et al., 2021 [174] |
MT (15 studies: 9 cohort; 6 nestedcase–control) |
N/A | 42,636 pregnant women (1848/40,788) |
Blood vitamin D levels | The result showed that lower levels of serum 25(OH)D were associated with a higher chance of GDM |
| Wu et al., 2023 [166] |
MT (20 RCT studies) | From 2 to 16 weeks | 1682 pregnant women with GDM diagnosed (837/845) |
From 50,000 IU of vitamin D3 2 times/day to 1200 IU daily |
Reduce serum LDL-C, TG, and TC levels and increase the serum HDL-C level. Reduce maternal and neonatal hyperbilirubinemia and hospitalization risk. |
| VITAMIN D, METABOLIC SYNDROME (MetS), AND CARDIOVASCULAR DISEASE (CVD) | |||||
| De Paula TP et al., 2017 [223] |
MT (7 RCTs) | From 3 to 52 weeks | 542 patients with T2DM (472/70) |
A single dose of vitamin D2 (100,000 IU) or vitamin D3 (100,000 IU or 200,000 IU) | Reduction in BP, especially in systolic BP |
| Ostadmohammadi et al., 2019 [221] |
MT (8 RCTs) | From 8 to 24 weeks | 630 adults with CVD (305/325) |
50,000 IU/week Vitamin D3 or 50,000 IU every two weeks or 300,000 IU single dose |
Improving glycemic control, HDL-C, and CRP levels; it did not affect TG, TC, and LDL-C levels |
| Hajhashemy Z. et al., 2021 [226] |
Dose–response MT (43 epidemiological studies: 38 cross-sectional; 1 nested case control; 4 cohort studies) |
N/A | 309.206 adults with or without MetS |
Blood Vitamin D levels in adults | Inverse association between serum vitamin D concentrations and risk of MetS |
| Qi K.J. et al., 2022 [222] |
MT (13 RCTs) | From 8 to 24 weeks | 1.076 adults with MetS (530/546) |
From 1000 IU/day Vitamin D3 to 50,000 IU/week | Decreased BP, FPG, HOMA-IR, and CRP levels; it did not affect HDL-C, LDL-C, TC, and TG levels |
I/C: intervention/control; IR: insulin resistance; MT: meta-analysis; RCTs: randomized controlled trials; IFG: impaired fasting glucose; GDM: gestational diabetes mellitus; T2DM: type 2 diabetes mellitus; PCOS: polycystic ovary syndrome; FBG: fasting blood glucose; HOMA-IR: homeostatic model assessment of insulin resistance; NAFLD: non-alcoholic fatty liver disease; HbA1c: glycated hemoglobin; SR: systematic review; IR: insulin resistance; T1DM: type 1 diabetes mellitus; N/A: not applicable; MetS: metabolic syndrome; CVD: cardiovascular disease; BP: blood pressure; TG: triglycerides; TC: total cholesterol; LDL-C: LDL-cholesterol; HDL-C: HDL-cholesterol; CRP: C-reactive protein.