The Role of Vitamin D Oral Supplementation in Insulin Resistance in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Abstract
:1. Introduction
2. Methods
2.1. Protocol and Registration
2.2. Eligibility Criteria
2.3. Inclusion Criteria
- Intervention studies (randomized controlled trials (RCTs) and double-blind randomized controlled trials (DB-RCTs)) that compared vitamin D supplementation (alone or in combination with other vitamins and minerals) with a placebo without any limitations on time of supplementation.
- English-language articles.
- Studies that enrolled women with a strict diagnosis of PCOS using the Rotterdam criteria of the European Society of Human Reproduction and Embryology (ESHRE)/American Society of Reproductive Medicine (ASRAM) [29].
- The vitamin D was administered orally as cholecalciferol (vitamin D3), ergocalciferol (vitamin D2), or an active form of vitamin D (1α-hydroxyvitamin D and 1,25-dihydroxyvitamin D (1,25(OH)2D)). Studies in which vitamin D was combined with other vitamins and minerals were also taken into consideration. Finally, we included studies that reported the most often assessed parameters in insulin resistance, such as fasting glucose, fasting insulin, and HOMA-IR.
2.4. Exclusion Criteria
- Studies performed in specific groups of patients (e.g., subjects with hyperparathyroidism, subjects suffering from hepatic disease or kidney disease, those with a history of bariatric surgery, pregnant or breast-feeding women, and studies performed in women with PCOS but without insulin resistance).
- Studies in which vitamin D was combined with metformin.
- Conference papers, and articles only available in abstract form (where the authors could not be contacted) were also excluded.
2.5. Data Extraction and Analysis
2.6. Assessment of the Risk of Bias in Studies
2.7. Statistical Analysis
3. Results
3.1. Search Results
3.2. Population and Study Characteristics
3.3. Effects of Vitamin D Supplementation on 25(OH)D Levels
3.4. Effects of Vitamin D Supplementation on Changes in Parameters Related to Insulin Resistance
3.5. Publication Bias
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Study | Country | Subjects (n) | Intervention | Supplemented Dose of Vitamin D | Vitamin D Supplements: Formulation and Manufacturer | Time of Intervention | Ethnicity |
---|---|---|---|---|---|---|---|
Abootorabi et al. [16], 2017 | Iran | 36 | Cholecalciferol (n = 19) Placebo (n = 17) | 50,000 IU/weekly | Capsules: D-Vitamin 50,000; Zahravi Pharm Co, Tabriz, Iran | 8 weeks | Asian: 100% |
Ardabili et al. [17], 2012 | Iran | 50 | Cholecalciferol (n = 24) Placebo (n = 26) | 50,000 IU every 20 days Placebo | Capsules: D-Vitin 50,000, Zahravi Pharm Co, Tabriz, Iran | 60 weeks | Asian: 100% |
Asemi et al. [18], 2014 a | Iran | 78 | Cholecalciferol (n = 26) Cholecalciferol + Calcium(n = 26) placebo (n = 26) | 50,000 IU/week 50,000 IU/week + 1000 mg/d Placebo | Tablets: Dana Pharmaceutical Company (Tabriz, Iran) and Barij Essence Pharmaceutical Company (Kashan, Iran). | 8 weeks | Asian: 100% |
Bonakdaran et al. [24], 2012 b | Iran | 31 | Calcitriol (n = 15) Placebo (n = 16) | 200 IU/d Placebo | Capsules: Zahravi, Tabriz, Iran | 12 weeks | Asian: 100% |
Gupta et al. [21], 2017 | India | 50 | Cholecalciferol (n = 25) Placebo (n = 25) | 60,000 IU/weekly Placebo | Not given | 12 weeks | Asian: 100% |
Irani et al. [15], 2015 | USA | 53 | Cholecalciferol (n = 35) Placebo (n = 18) | 50,000 IU/weekly Placebo | Capsules: manufacturer not given | 8 weeks | Vitamin D group: Hispanic: 69.4%; Asian: 25%; Black: 5.5% Placebo group: Hispanic: 72.2%; Asian: 22.2%; Black: 5.5% |
Jamilian et al. [2], 2017 | Iran | 90 | Cholecalciferol (n = 30) Cholecalciferol (n = 30) Placebo (n = 30) | 1000 IU/d 4000 IU/d Placebo | Capsules: Zahravi Pharmaceutical Company (Tabriz, Iran) and Barij Essence Pharmaceutical Company Kashan, Iran | 12 weeks | Asian: 100% |
Jamilian et al. [22], 2017 | Iran | 60 | Cholecalciferol+Magnesium+Zinc+Calcium (n = 30) Placebo (n = 30) | 200 IU + 100 mg + 4 mg + 400 mg/d Placebo | Tablets: Vitane (Wolfratshausen, Germany) and Barij Essence Pharmaceuticals (Kashan, Iran), | 12 weeks | Asian: 100% |
Karamali et al. [19], 2018 | Iran | 55 | Cholecalciferol + Calcium + Vitamin K (n = 28) Placebo (n = 27) | 200 IU + 500 mg + 90 μg/d Placebo | Capsules: Arian SalamtSina (Tehran, Iran) and Barij Essence Pharmaceutical Company(Kashan, Iran) | 8 weeks | Asian: 100% |
Maktabi et al. [23], 2017 | Iran | 70 | Cholecalciferol (n = 35) Placebo (n = 35) | 50,000 IU every 2 weeks Placebo | Capsules: Zahravi, Tabriz, Iran | 12 weeks | Asian: 100% |
Raja-Khan et al. [20], 2014 | USA | 28 | Cholecalciferol (n = 13) Placebo (n = 15) | 12,000 IU/d Placebo | Gel caps: Maximum D3 (with soy lecithin oil): BTR Group, Inc. (Pittsfield, IL, USA) | 12 weeks | N/A |
Study | Supplemented Dose of Vitamin D | Study Groups | Age (Years) Mean ± SD | BMI (kg/m2) Mean ± SD | Serum 25(OH)D (ng/mL)Concentration Mean ± SD | |
---|---|---|---|---|---|---|
Before Supplementation | After Supplementation | |||||
Abootorabi et al. [16], 2017 | Cholecalciferol Placebo | SG PG | 26.2 ± 4.6 22.8 ± 4.4 | N/A | 8.65 ± 4.3 9.80 ± 5.1 | 36.9 ± 8.4 *** 13.4 ± 7.1 |
Ardabili et al. [17], 2012 | Cholecalciferol Placebo | SG PG | 26.8 ± 4.7 27.0 ± 3.7 | 29.1 ± 4.6 28.3 ± 3.5 | 6.9 ± 2.8 | 23.4 ± 6.1 *** |
Asemi et al. [18], 2014a | Cholecalciferol Cholecalciferol + Calcium placebo | SG SG PG | 25.6 ± 4.4 24.9 ± 5.1 24.3 ± 5.2 | 29.3 ± 3.9 27.3 ± 5.3 27.5 ± 5.2 | 11.6 ± 4.7 15.1 ± 3.6 14.0 ± 4.1 | 23.4 ± 7.1 ** 26.8 ± 7.8 *** 14.4 ± 4.7 |
Bonakdaran et al. [24], 2012b | Calcitriol Placebo | SG PG | 24.7 ± 3.3 25.2 ± 7.9 | 24.8 ± 5.3 25.3 ± 5.1 | 11.4 ± 8.2 19.9 ± 16.5 | 20.1 ± 16.2 19.0 ± 15.3 |
Gupta et al. [21], 2017 | Cholecalciferol Placebo | SG PG | 26.0 ± 3.7 26.6 ± 3.7 | 24.9 ± 2.8 25.6 ± 2.0 | 18.56 ± 9.7 | 44.90 ± 9.04 *** |
Irani et al. [15], 2015 | Cholecalciferol Placebo | SG PG | 30.5 ± 1.0 29.6 ± 1.7 | 30.0 ± 1.0 28.0 ± 1.6 | 16.3 ± 0.9 17.0 ± 1.8 | 43.2 ± 2.4 ** 17.4 ± 1.9 |
Jamilian et al. [22], 2017 | Cholecalciferol+Magnesium+Zinc+Calcium Placebo | SG PG | 18–40 | N/A | +7.9 ± 8.4 *** b +0.1 ± 8.4 | |
Jamilian et al. [2], 2017 | Cholecalciferol Cholecalciferol Placebo | SG low dose SG high dose PG | 26 ± 5.0 28 ± 5.0 25 ± 5.0 | 33 ± 5 31 ± 6 30 ± 6 | 12.6 ± 3.4 12.6 ± 2.7 12.9 ± 2.4 | 18.5 ± 4.9 * 24.6 ± 3.3 * 13.1 ± 2.5 |
Karamali et al. [19], 2018 | Cholecalciferol + calcium + vitamin K Placebo | SG PG | 23.5 ± 4.2 23.3 ± 3.4 | 24.2 ± 4.8 24.3 ± 3.9 | 14.7 ± 2.5 14.8 ± 3.9 | 20.0 ± 3.0 *** 14.5 ± 5.0 |
Maktabi et al. [23], 2017 | Cholecalciferol Placebo | SG PG | 18–40 a | N/A | 12.8 ± 4.5 14.5 ± 5.1 | 27.5 ± 9.8 *** 14.4 ± 5.2 |
Raja-Khan et al. [20], 2014 | Cholecalciferol Placebo | SG PG | 28.2 ± 5.2 28.7 ± 5.6 | 37.2 ± 4.5 35.1 ± 9.8 | 19.95 ± 9.5 22.20 ± 6.9 | 67.4 ± 28.6 *** 22.5 ± 7.0 |
Study | Supplemented Dose of Vitamin D | Study Groups | Fasting Glucose (mg/dL) Mean ± SD | Fasting Insulin (μLU/mL) Mean ± SD | HOMA-IR Mean ± SD | |||
---|---|---|---|---|---|---|---|---|
Before | After | Before | After | Before | After | |||
Abootorabi et al. [16], 2017 | Cholecalciferol Placebo | SG PG | 86.7 ± 6.8 84.2 ± 5.9 | 79.1 ± 7.1 *** 85.9 ± 7.9 | 14.7 ± 7.5 8.2 ± 5.8 | 15.9 ± 7.3 9.6 ± 3.3 | 2.8 ± 1.3 1.7 ± 1.2 | 2.8 ± 1.4 2.0 ± 0.7 |
Ardabili et al. [17], 2012 | Cholecalciferol Placebo | SG PG | 99.8 ± 10.1 101.5 ± 10.6 | 96.6 ± 9.9 98.8 ± 14.6 | 12.5 ± 15.1 9.9 ± 5.3 | 13.3 ± 9.7 10.0 ± 4.1 | 3.2 ± 4.1 2.5 ± 1.4 | 3.2 ± 2.6 2.5 ± 1.1 |
Asemi et al. [18], 2014 a | Cholecalciferol Cholecalciferol + calcium placebo | SG SG PG | 87.3 ± 16.4 81.6 ± 10.0 67.6 ± 11.7 | 86.8 ± 16.1 76.4 ± 13.3 * 73.5 ± 23.8 | 13.5 ± 9.9 11.1 ± 14.2 12.0 ± 5.6 | 12.4 ± 5.5 * 7.8 ± 3.6 * 15.1 ± 7.1 | 3.1 ± 2.8 2.2 ± 2.8 2.0 ± 1.1 | 2.8 ± 1.6 * 1.5 ± 0.7 * 2.8 ± 1.9 |
Bonakdaran et al. [24], 2012 b | Calcitriol Placebo | SG PG | 81.7 ± 8.6 86.3 ± 5.4 | 89.0 ± 12.3 87.3 ± 5.3 | 18.3 ± 30.4 13.6 ± 14.6 | 13.1 ± 14.8 8.6 ± 5.0 | 4.2 ± 6.8 2.8 ± 2.9 | 2.7 ± 3.1 1.9 ± 1.0 |
Gupta et al. [21], 2017 | Cholecalciferol Placebo | SG PG | 88.2 ± 9.3 91.3 ± 8.4 | 82.4 ± 8.0 * 87.6 ± 9.9 | 10.3 ± 20.0 4.6 ± 0.6 | 5.0 ± 3.2 * 4.6 ± 0.6 | 2.4 ± 4.9 1.0 ± 0.6 | 1.0 ± 0.6 * 1.0 ± 0.2 |
Irani et al. [15], 2015 | Cholecalciferol Placebo | SG PG | N/A | N/A | N/A | N/A | 2.1 ± 0.4 1.6 ± 0.3 | 2.0 ± 0.2 1.5 ± 0.2 |
Jamilian et al. [22], 2017 | Cholecalciferol Cholecalciferol Placebo | SG low dose SG high dose PG | N/A | N/A | N/A | N/A | 3.2 ± 0.4 3.2 ± 0.4 3.0 ± 0.3 | 2.9 ± 0.6 2.7 ± 0.4 * 3.1 ± 0.7 |
Jamilian et al. [2], 2017 | Cholecalciferol+Magnesium+Zinc+Calcium Placebo | SG PG | 86.6 ± 6.9 90.0 ± 4.8 | 86.7 ± 7.5 91.1 ± 5.9 | 12.9 ± 4.4 11.2 ± 3.9 | 11.0 ± 4.6 11.6 ± 4.5 | 2.8 ± 0.9 2.5 ± 0.9 | 2.4 ± 1.1 2.6 ± 1.0 |
Karamali et al. [19], 2018 | Cholecalciferol + calcium + vitamin K Placebo | SG PG | 84.2 ± 6.9 83.6 ± 13.0 | 84.5 ± 6.7 88.6 ± 20.5 | 11.8 ± 4.7 10.4 ± 5.3 | 9.9 ± 3.7 ** 12.2 ± 6.1 | 2.4 ± 1.0 2.1 ± 1.0 | 2.0 ± 0.8 ** 2.5 ± 1.3 |
Maktabi et al. [23], 2017 | Cholecalciferol Placebo | SG PG | 91.0 ± 6.1 93.8 ± 7.8 | 87.8 ± 7.6 * 94.3 ± 9.8 | 9.6 ± 4.5 9.1 ± 7.3 | 8.2 ± 2.8 ** 11.7 ± 6.5 | 2.2 ± 1.1 2.1 ± 1.7 | 1.8 ± 0.6 ** 2.7 ± 1.6 |
Raja-Khan et al. [20], 2014 | Cholecalciferol Placebo | SG PG | 84.9 ± 9.5 83.7 ± 9.3 | 83.8 ± 8.0 77.6 ± 14.7 | 26.31 ± 9.6 27.1 ± 15.8 | 38.1 ± 37.6 28.7 ± 14.6 | 5.5 ± 1.8 5.8 ± 3.9 | 7.8 ± 7.4 5.7 ± 3.0 |
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Łagowska, K.; Bajerska, J.; Jamka, M. The Role of Vitamin D Oral Supplementation in Insulin Resistance in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients 2018, 10, 1637. https://doi.org/10.3390/nu10111637
Łagowska K, Bajerska J, Jamka M. The Role of Vitamin D Oral Supplementation in Insulin Resistance in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2018; 10(11):1637. https://doi.org/10.3390/nu10111637
Chicago/Turabian StyleŁagowska, Karolina, Joanna Bajerska, and Małgorzata Jamka. 2018. "The Role of Vitamin D Oral Supplementation in Insulin Resistance in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials" Nutrients 10, no. 11: 1637. https://doi.org/10.3390/nu10111637
APA StyleŁagowska, K., Bajerska, J., & Jamka, M. (2018). The Role of Vitamin D Oral Supplementation in Insulin Resistance in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients, 10(11), 1637. https://doi.org/10.3390/nu10111637