The Effect of Folic Acid Supplementation on Endothelial Function and Arterial Stiffness Markers in Adults: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Protocol and Registration
2.2. Information Sources and Search Strategy
2.3. Inclusion and Exclusion Criteria
2.4. Data Collection Process, Extraction and Analysis
2.5. Data Item
- 1.
- General information: title of the article, journal name, main author and publication year;
- 2.
- Study characteristics: name and design, country (region), sample size (total number and number of subjects for each group (which included and completed the trial) and study design;
- 3.
- Type and time of intervention: studies that compared the effect of oral folic acid (form and dose) supplementation with placebo on endothelial function (the control group received a placebo or other nutrients excluding folic acid) with an intervention duration of at least two weeks;
- 4.
- Study population characteristics: age (≥18 years old), sex (% of women), body mass index (BMI (kg/m2)) and health condition;
- 5.
- Outcomes measured:
- 5.1.
- Main outcome:
- Endothelial function: flow-mediated dilation (FMD (%)).
- 5.2.
- Endothelial function: flow-mediated dilation (FMD (%)).
- Arterial stiffness parameters: pulse wave velocity (PWV (m/s)); pulse wave analysis (PWA), augmentation index (AIx (%));
- Endothelial function parameters: asymmetric dimethylarginine (ADMA (μmol/L)), endothelial nitric oxide synthase (eNOS (ng/mL)), monocyte chemotactic protein (MCP-1 (pg/mL)), matrix metalloproteinase (MMP), plasminogen activator inhibitor-1 (PAI-1 (AU/mL)), soluble vascular cell adhesion molecule-1 (sVCAM-1 (ng/mL)), intercellular adhesion molecule-1 (ICAM-1 (ng/mL)), vascular endothelial growth factor (VEGF (pg/mL)).
2.6. Risk of Bias of Individual Studies
2.7. Statistical Analysis
3. Results
3.1. Search Result
3.2. Characteristics of Included Studies
3.3. Characteristics of Intervention
3.4. The Effect of Folic Acid Supplementation on Flow-Mediated Dilation
3.5. The Effect of Folic Acid Supplementation on Pulse Wave Velocity
3.6. The Effect of Folic Acid Supplementation on Monocyte Chemotactic Protein 1
3.7. The Effect of Folic Acid Supplementation on Other Endothelial Parameters
3.8. Subgroup Analysis
3.9. Risk of Bias
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Author | Year | Country (Region) | Groups | n Included | n Completed | Study Design | Studied Population | Age (Years) 1 | BMI (kg/m2) 1 | Sex [% of Women] |
---|---|---|---|---|---|---|---|---|---|---|
Li et al. [39] | 2020 | China (Asia) | Intervention 2 | 60 | 55 | RCT parallel | Elderly subjects with mild cognitive impairment | 70.33 ± 7.70 | 24.41 ± 2.47 | 60 |
Intervention 3 | 60 | 53 | 70.20 ± 6.13 | 25.47 ± 3.01 | 60 | |||||
Intervention 4 | 60 | 53 | 71.55 ± 6.62 | 24.70 ± 2.52 | 60 | |||||
Control | 60 | 51 | 70.38 ± 6.73 | 24.30 ± 2.93 | 55 | |||||
Ma et al. [61] | 2019 | China (Asia) | Intervention 3 | 60 | 58 | RCT parallel | Elderly subjects with mild cognitive impairment | 68.42 ± 3.62 | NI | 63 |
Intervention 5 | 60 | 58 | 69.47 ± 2.88 | 65 | ||||||
Intervention 6 | 60 | 58 | 69.16 ± 2.46 | 65 | ||||||
Control | 60 | 57 | 68.54 ± 3.90 | 63 | ||||||
Grigoletti et al. [63] | 2018 | Brazil (South America) | Intervention 3 | 6 | NI | RCT parallel | HIV-infected individuals, antiretroviral therapy (at least 6 months) with undetectable viral load (<50 copies/mL) and CD4 count > 200 cells/mm3 | 53 ± 3 8 | NI | 50 |
Intervention 7 | 5 | 52 ± 3 8 | 40 | |||||||
Control | 5 | 48 ± 3 8 | 60 | |||||||
Hoch et al. [64] | 2009 | USA (North America) | Intervention | NI | 8 | RCT parallel | Eumenorrheic woman who were not taking birth control pills and who ran at least 20 miles/week | 25.0 ± 1.4 9 | 20.7 ± 0.6 9 | 100 |
Control | 5 | 22.4 ± 0.9 9 | 24.4 ± 1.2 9 | 100 | ||||||
Khandanpour et al. [27] | 2009 | United Kingdom (Europe) | Intervention 3 | 46 | 45 | RCT parallel | Subjects with peripheral arterial disease | 70.1 ± 9.0 | 27.5 ± 4.5 | 69 |
Intervention 10 | 51 | 48 | 69.7 ± 7.6 | 27.3 ± 3.6 | 71 | |||||
Control | 46 | 40 | 69.2 ± 8.2 | 26.8 ± 3.6 | 63 | |||||
Moens et al. [65] | 2007 | Belgium (Europe) | Intervention | NI | 20 | RCT crossover | Subjects with acute myocardial infarction | 57 ± 11 | NI | 10 |
Control | 20 | 56 ± 14 | 15 | |||||||
Shirodaria et al. [40] | 2007 | United Kingdom (Europe) | Intervention 11 | 56 | 20 | RCT parallel | Subjects with coronary artery disease | 62.2 ± 7.6 | 28.2 ± 4.0 | 25 |
Intervention 12 | 22 | 62.2 ± 8.0 | 28 ± 3.8 | 9 | ||||||
Control | 14 | 64 ± 8.6 | 26.9 ± 4.5 | 14.3 | ||||||
Yilmaz et al. [66] | 2007 | Turkey (Asia) | Intervention 3 | 20 | 20 | RCT parallel | Subjects with elevated plasma homocysteine levels (>15 μmol/L) and unequivocal angiographic evidence of coronary artery disease (>50% stenosis in one or more vessels) | 52.2 ± 11.9 | 27.2 ± 3.8 | 35 |
Intervention 13 | 20 | 16 | 64.8 ± 9.0 | 27.8 ± 3.8 | 15 | |||||
Control | 20 | 18 | 65.5 ± 7.6 | 28.3 ± 4 | 10 | |||||
Austen et al. [28] | 2006 | Australia (Australia) | Intervention | NI | 10 | RCT crossover | Renal transplant recipients | 45.5 ± 11.8 | NI | 30 |
Control | ||||||||||
Moat et al. [41] | 2006 | United Kingdom (Europe) | Intervention 11 | NI | 30 | RCT parallel | Subjects with coronary artery disease | 61 ± 7 | 28.5 ± 4.4 | 10 |
Intervention 12 | 25 | 60 ± 7 | 29.9 ± 4.4 | 16 | ||||||
Control | 29 | 61 ± 7 | 29.6 ± 4.1 | 13.8 | ||||||
Olthof et al. [53] | 2006 | Netherlands (Europe) | Intervention | 40 | 39 | RCT crossover | Healthy subjects | 59 ± 5 | 25.2 ± 2.8 | NI |
Control | ||||||||||
Solini et al. [62] | 2006 | Italy (Europe) | Intervention | 30 | 30 | RCT parallel | Healthy volunteers with normal glucose tolerance and overweight | 50 ± 7 | 27.5 ± 0.6 | 73.3 |
Control | 30 | 30 | 49 ± 8 | 27.4 ± 0.6 | 63.3 | |||||
Spoelstra-de Man et al. [56] a | 2006 | Netherlands (Europe) | Intervention | 28 | 23 | RCT parallel | Subjects with a diabetes mellitus type 2, a fasting homocysteine concentration of ≥14 μmol/L and a urinary albumin-to-creatinine ratio of at least 1 mg/mmol | 64 ± 9 | 29 ± 4 | 39 |
Control | 23 | 18 | 66 ± 9 | 29 ± 3 | 44 | |||||
Title et al. [58] | 2006 | Canada (North America) | Intervention | NI | 19 | RCT crossover | Subjects with diabetes mellitus type 2 | 54.5 ± 5.9 | NI | 52.6 |
Control | ||||||||||
Zoungas et al. [50] b | 2006 | Australia, New Zealand (Oceania) | Intervention | 355 | 156 | RCT parallel | Subjects with chronic renal failure of any cause | 56 ± 13 | 26 ± 5 | 26.9 |
Control | 159 | 56 ± 14 | 27± 4 | 37.7 | ||||||
Mangoni et al. [26] | 2005 | Australia (Australia) | Intervention | NI | 13 | RCT parallel | Subjects with diabetes mellitus type 2 | 55.3 ± 4.3 | 30.5 ± 4.0 | 38.5 |
Control | 13 | 57.6 ± 4.7 | 32.3 ± 6.5 | 46 | ||||||
Williams et al. [51] | 2005 | Australia (Australia) | Intervention | NI | 41 | RCT crossover | Subjects with normal or high-normal ambulatory blood pressure (systolic: >130 to <145 mm Hg; diastolic: >80 to <90 mm Hg) | 32 ± 7 | 24 ± 4 | NI |
Control | ||||||||||
Durga et al. [57] | 2005 | Netherlands (Europe) | Intervention | 530 | 521 | RCT parallel | Men and postmenopausal women aged 50 to 70 years | 60 ± 5 | 27 ± 3 | 29.9 |
Control | 60 ± 6 | 27 ± 4 | 26.3 | |||||||
Doshi et al. [42] * | 2004 | United Kingdom (Europe) | Intervention [31] | 52 | 50 | RCT crossover | Subjects with coronary heart disease | 57 ± 8 | 28.5 ± 4.4 | 12 |
Control [31] | ||||||||||
Lekakis et al. [67] | 2004 | Greece (Europe) | Intervention | NI | 17 | RCT parallel | Hypercholesterolaemic subjects taking statins | 55.7 ± 8.3 | NI | 17.6 |
Control | 17 | 57.3 ± 8.8 | 11.8 | |||||||
Spoelstra-de Man et al. [54] a | 2004 | Netherlands (Europe) | Intervention | 28 | 23 | RCT parallel | Subjects with a diabetes mellitus type 2, a fasting homocysteine concentration of ≥14 μmol/L and a urinary albumin-to-creatinine ratio of at least 1 mg/mmol | 63.7 ± 8.6 | 29.3 ± 3.9 | 39 |
Control | 23 | 18 | 66.1 ± 8.5 | 28.8 ± 3.4 | 44 | |||||
Woodman et al. [29] | 2004 | Australia (Australia) | Intervention | NI | 26 | RCT crossover | Healthy hyperhomocysteinaemic subjects | 49 ± 2 | 28.1 ± 1.0 | 30.8 |
Control | ||||||||||
Zoungas et al. [52] b | 2004 | Australia, New Zealand (Australia) | Intervention | NI | 315 | RCT parallel | Subjects with chronic renal failure | 58.2 ± 10.2 | NI | 32.4 |
Control | 213 | 56.6 ± 13.6 | 33.3 | |||||||
Doshi et al. [43] * | 2003 | United Kingdom (Europe) | Intervention [31] | NI | 50 | RCT crossover | Subjects with coronary heart disease | 57 ± 8 | 28.5 ± 4.4 | 12 |
Control [31] | ||||||||||
Intervention [29] | 33 | RCT parallel | Subjects with coronary heart disease | 56 ± 7 | 28.9 ± 5.99 | 9 | ||||
Control [29] | ||||||||||
Doshi et al. [44] | 2002 | United Kingdom (Europe) | Intervention | NI | 16 | RCT parallel | Subjects with coronary heart disease | 56 ± 7 | 28.9 ± 5.99 | 9 |
Control | 17 | |||||||||
Mangoni et al. [45] | 2002 | United Kingdom (Europe) | Intervention | NI | 12 | RCT parallel | Chronic cigarette smokers | 39.7 ± 3.4 | 25.7 ± 0.8 | 66.7 |
Control | 12 | 36.0 ± 3.6 | 24.9 ± 0.9 | 58.3 | ||||||
Doshi et al. [46] | 2001 | United Kingdom (Europe) | Intervention | 52 | 50 | RCT crossover | Subjects with coronary artery disease | 57 ± 8 | 28.5 ± 4.4 | 12 |
Control | ||||||||||
Miner et al. [60] | 2001 | Canada (North America) | Intervention 14 | 37 | 11 | RCT parallel | Cardiac transplant recipients | 55 ± 1 | NI | 9.1 |
Intervention 3 | 12 | 56 ± 1 | 16.7 | |||||||
Control | 8 | 48 ± 1 | 14.3 | |||||||
Pullin et al. [47] | 2001 | United Kingdom (Europe) | Intervention 3 | NI | 42 | RCT crossover | Healthy subjects | 39 ± 12 | NI | 58 |
Intervention 15 | 42 | |||||||||
Control | 42 | |||||||||
Thambyrajah et al. [48] | 2001 | United Kingdom (Europe) | Intervention | 90 | 43 | RCT parallel | Subjects with >50% stenosis in one or more vessels | 63.0 ± 8.2 | 28.6 ± 4.7 | 14 |
Control | 43 | 63.4 ± 7.2 | 27.2 ± 3.5 | 11.6 | ||||||
Thambyrajah et al. [49] | 2000 | United Kingdom (Europe) | Intervention | 50 | 47 | RCT parallel | Subjects with chronic renal failure (serum creatinine >130 mmol/L) and a plasma homocysteine concentration >12 mmol/L | 61 (57–64) 16 | 28.2 (26.6–29.8) 16 | 26 |
Control | 50 | 44 | 62 (59–66) 16 | 27.5 (26.1–28.8) 16 | 28 | |||||
Title et al. [59] | 2000 | Canada (North America) | Intervention 3 | NI | 25 | RCT parallel | Subjects with coronary artery disease | 57.2 ± 9.8 | NI | 24 |
Intervention 17 | 25 | 58.8 ± 11.6 | 24 | |||||||
Control | 25 | 60.6 ± 8.6 | 16 | |||||||
Wilmink et al. [55] | 2000 | Netherlands (Europe) | Intervention | NI | 20 | RCT crossover | Healthy subjects | 23 ± 3.4 | 21.9 ± 2.7 | 50 |
Control | 20 | 22.8 ± 2.6 | ||||||||
Bellamy et al. [37] | 1999 | United Kingdom (Europe) | Intervention | NI | 10 | RCT crossover | Healthy volunteers-blood donors and members of hospital staff | NI | NI | NI |
Control | 8 | |||||||||
Woo et al. [38] | 1999 | China (Asia) | Intervention | 17 | RCT crossover | Healthy volunteers who had no history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease or family history of premature atherosclerosis | 54 ± 10 | NI | NI | |
Kunz et al. [36] | 1999 | France (Europe) | Intervention | 63 | 25 | RCT parallel | Stable chronic haemodialysis patients who did not receive anti-epileptic drugs or other folate antagonists or oestrogens; no vitamin B12 or folate supplementation over the past 12 months | 59 ± 13 | NI | 30 |
Control | 28 |
Author | Year | Groups | Characteristic of Intervention | Form | Dose (per Day) | Time of Intervention (Weeks) |
---|---|---|---|---|---|---|
Li et al. [39] | 2020 | Intervention | Folic acid + docosahexaenoic acid | Tablets + capsules | 800 μg + 800 mg | 26 |
Intervention | Folic acid | 800 μg | ||||
Intervention | Docosahexaenoic acid | 800 mg | ||||
Control | Placebo (corn starch + soybean oil) | NI | ||||
Ma et al. [61] | 2019 | Intervention | Folic acid | Tablets | 800 μg | 24 |
Intervention | Vitamin B12 | 25 µg | ||||
Intervention | Folic acid + vitamin B12 | 800 μg + 25 µg | ||||
Control | No intervention | NI | NI | |||
Grigoletti et al. [63] | 2018 | Intervention | Folinic acid | NI | 5 mg | 4 |
Intervention | Aerobic exercise training | - | ||||
Control | Placebo | NI | ||||
Control | Metformin + placebo | 1700 mg + NI | ||||
Hoch et al. [64] | 2009 | Intervention | Folic acid | NI | 10 mg | 6 |
Control | Placebo | NI | ||||
Khandanpour et al. [27] | 2009 | Intervention | Folic acid | Capsules | 400 μg | 16 |
Intervention | 5-MTHF | 400 μg | ||||
Control | Placebo | NI | ||||
Moens et al. [65] | 2007 | Intervention | Folic acid | NI | 10 mg | 6 |
Control | Placebo | NI | ||||
Shirodaria et al. [40] | 2007 | Intervention | Folic acid | NI | 400 μg | 7 |
Intervention | Folic acid | 5 mg | ||||
Control | Placebo | NI | ||||
Yilmaz et al. [66] | 2007 | Intervention | Folic acid | NI | 5 mg | 8 |
Intervention | N-acetylcysteine | 600 mg | ||||
Control | Placebo | NI | ||||
Austen et al. [28] | 2006 | Intervention | Folate | NI | 5 mg | 14 |
Control | Placebo | NI | ||||
Moat et al. [41] | 2006 | Intervention | Folic acid | Tablets | 400 μg | 6 |
Intervention | Folic acid | 5 mg | ||||
Control | Placebo | NI | ||||
Olthof et al. [53] | 2006 | Intervention | Folic acid + lactose | NI | 0.8 mg + 6 g | 6 |
Control | Placebo (lactose) | 6 g | ||||
Solini et al. [62] | 2006 | Intervention | Folic acid + hypocaloric diet (1400 kcal/day, 55% carbohydrate, 25% protein and 20% fat) | NI | 2.5 mg | 12 |
Control | Placebo + hypocaloric diet (1400 kcal/day, 55% carbohydrate, 25% protein and 20% fat) | NI | ||||
Spoelstra-de Man et al. [54,56] a | 2006, 2004 | Intervention | Folic acid | Tablets | 5 mg | 26 |
Control | Placebo | NI | ||||
Title et al. [58] | 2006 | Intervention | Folic acid | Capsules | 10 mg | 2 |
Control | Placebo | NI | ||||
Zoungas et al. [50] b | 2006 | Intervention | Folic acid | NI | 15 mg | 188 1 |
Control | Placebo | NI | ||||
Mangoni et al. [26] | 2005 | Intervention | Folic acid | NI | 5 mg | 4 |
Control | Placebo | NI | ||||
Williams et al. [51] | 2005 | Intervention | Folic acid | NI | 5 mg | 3 |
Control | Placebo | NI | ||||
Durga et al. [57] | 2005 | Intervention | Folic acid | Capsules | 0.8 mg | 52 |
Control | Placebo | NI | ||||
Doshi et al. [42] * | 2004 | Intervention | Folic acid | Tablets | 5 mg | 6 |
Control | Placebo | NI | ||||
Lekakis et al. [67] | 2004 | Intervention | Folic acid | NI | 5 mg | 4 |
Control | Placebo | NI | ||||
Woodman et al. [29] | 2004 | Intervention | Folic acid | NI | 5 mg | 8 |
Control | Placebo | NI | ||||
Zoungas et al. [52] b | 2004 | Intervention | Folic acid | Tablets | 15 mg | 206 |
Control | Placebo | NI | ||||
Doshi et al. 2 [43] * | 2003 | Intervention | Folic acid | NI | 5 mg | 6 |
Control | Placebo | NI | ||||
Doshi et al. 3 [44] | 2002 | Intervention | Folic acid | NI | 5 mg | 6 |
Control | Placebo | NI | ||||
Mangoni et al. [45] | 2002 | Intervention | Folic acid | NI | 5 mg | 4 |
Control | Placebo | NI | ||||
Doshi et al. [46] | 2001 | Intervention | Folic acid | Tablets | 5 mg | 6 |
Control | Placebo | NI | ||||
Miner et al. [60] | 2001 | Intervention | Pyridoxine | NI | 100 mg | 10 |
Intervention | Folic acid | 5 mg | ||||
Control | Placebo | NI | ||||
Pullin et al. [47] | 2001 | Intervention | Folic acid | Tablets | 400 μg | 17 |
Intervention | Foods naturally high in folate and folic acid–fortified foods | - | ~400 μg | |||
Control | Placebo | NI | NI | |||
Thambyrajah et al. [48] | 2001 | Intervention | Folic acid | NI | 5 mg | 12 |
Control | Placebo | NI | ||||
Thambyrajah et al. [49] | 2000 | Intervention | Folic acid | NI | 5 mg | 12 |
Control | Placebo | NI | ||||
Title et al. [59] | 2000 | Intervention | Folic acid | Capsules | 5 mg | 17 |
Intervention | Folic acid + vitamin C + vitamin E | 5 mg + 2 g + 800 IU | ||||
Control | Placebo | NI | ||||
Wilmink et al. [55] | 2000 | Intervention | Folic acid | NI | 10 mg | 2 |
Control | Placebo | NI | ||||
Bellamy et al. [37] | 1999 | Intervention | Folic acid | NI | 5 mg | 6 |
Control | Placebo | NI | ||||
Woo et al. [38] | 1999 | Intervention | Folic acid | NI | 10 mg | 4 |
Control | Placebo | NI | ||||
Kunz et al. [36] | 1999 | Intervention | Folic acid | NI | 10 mg | 8 |
Control | Placebo | NI | ||||
Control | No intervention | NI |
Author | Year | Group | FMD (%) | PWV (m/s) | Alx (%) | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Pre | Post | Changes (%) | Pre | Post | Changes (%) | Pre | Post | Changes (%) | |||
Grigoletti et al. [63] | 2018 | Intervention 1 | NI | NI | 7.33 ± 2.44 3−5 | NI | NI | NI | NI | NI | NI |
Intervention 2 | 0.04 ± 0.83 3−5 | ||||||||||
Control | 6.54 ± 0.91 3−5 | ||||||||||
Hoch et al. [64] | 2009 | Intervention | 6.6 ± 0.8 3 | 10.0 ± 0.9 3 | 3.5 ± 0.6 3 | NI | NI | NI | NI | NI | NI |
Control | 6.5 ± 0.7 3 | 6.65 ± 0.7 3 | 0.11 ± 0.2 3 | ||||||||
Khandanpour et al. [27] | 2009 | Intervention | NI | NI | NI | 10.60 (8.30–13.90) 6,7 9.40 (7.70–12.50) 6,8 | NI | −0.90 (−2.10, 0.00) 6,7,9 −0.50 (−1.50, 0.30) 6,8,9 | NI | NI | NI |
Control | 11.55 (9.95–15.60) 6,7 9.80 (8.15–12.00) 6,8 | ||||||||||
Moens et al. [65] | 2007 | Intervention | 3.98 ± 0.35 3 | 6.44 ± 0.56 3 | NI | NI | NI | NI | NI | NI | NI |
Control | 4.01 ± 0.34 3 | 4.46 ± 0.38 3 | |||||||||
Shirodaria et al. [40] | 2007 | Intervention 10 | 7.71 ± 1.26 3,5 | 11.95 ± 1.53 3,5 | NI | 9.03 ± 1.023,12 | 7.62 ± 0.78 3,12 | –1.41 ± 0.48 3,12 | NI | NI | NI |
Intervention 11 | 7.90 ± 1.28 3,5 | 13.12 ± 1.7 3,5 | 8.50 ± 0.613,12 | 7.33 ± 0.51 3,12 | –1.17 ± 0.47 3,12 | ||||||
Control | 9.71 ± 1.02 3,5 | 7.19 ± 1.52 3,5 | 7.93 ± 0.713,12 | 8.22 ± 0.90 3,12 | 0.29 ± 0.35 3,12 | ||||||
Yilmaz et al. [66] | 2007 | Intervention 1 | 5.3 ± 2.2 14 | 12.0 ± 6.3 14 | 6.7 15 | NI | NI | NI | NI | NI | NI |
Intervention13 | 6.0 ± 2.4 14 | 10.4 ± 3.2 14 | 4.4 15 | ||||||||
Control | 5.8 ± 1.9 14 | 6.1 ± 2.7 14 | 0.3 15 | ||||||||
Moat et al. [41] | 2006 | Intervention 10 | 27.3 ± 54.5 14,16 | 39.3 ± 31.9 14,16 | NI | NI | NI | NI | NI | NI | NI |
Intervention 11 | 24.4 ± 26.3 14,16 | 99.6 ± 35.7 14,16 | |||||||||
Control | 20.3 ± 31.0 14,16 | 33.5 ± 21.6 14,16 | |||||||||
Olthof et al. [53] | 2006 | Intervention | NI | 2.8 ± 1.9 14 | NI | NI | NI | NI | NI | NI | NI |
Control | 2.8 ± 1.8 14 | ||||||||||
Title et al. [58] | 2006 | Intervention | NI | 5.8 ± 4.8 14 | NI | NI | NI | NI | NI | NI | NI |
Control | NI | 3.2 ± 2.7 14 | |||||||||
Zoungas et al. [50] b | 2006 | Intervention | NI | NI | NI | –0.31 (–1.20–0.57) 9,17,18 | 0.1 (–5.3–5.5) 9,18 | ||||
Control | |||||||||||
Mangoni et al. [26] | 2005 | Intervention | NI | NI | NI | 10.1 ± 0.6 3,19 10.8 ± 0.7 3,20 | NI | +0.7 ± 0.6 3,9,19 −0.1 ± 0.6 3,9,20 | NI | NI | NI |
Control | 10.0 ± 0.6 3,19 10.9 ± 0.8 3,20 | +0.1 ± 0.4 3,9,19 +0.3 ± 0.4 3,9,20 | |||||||||
Williams et al. [51] | 2005 | Intervention | NI | NI | NI | 7.2 ± 0.9 14,20 10.6 ± 1.5 14,21 | NI | –0.09 ± 0.21 9,14,21 –0.10 ± 0.11 9,14,20 | NI | NI | NI |
Control | 0.19 ± 0.25 9,14,21 0.09 ± 0.10 9,14,20 | ||||||||||
Doshi et al. [42] * | 2004 | Intervention | 52 ± 34 14,16 | 110 ± 43 14,16 | NI | NI | NI | NI | NI | NI | NI |
Control | 46 ± 33 14,16 | 47 ± 35 14,16 | |||||||||
Lekakis et al. [67] | 2004 | Intervention | 4.7 ± 3.2 14 | 7.1 ± 3.1 14 | NI | NI | NI | NI | NI | NI | NI |
Control | 5.7 ± 3.8 14 | 5.6 ± 2.2 14 | |||||||||
Woodman et al. [29] | 2004 | Intervention | 7.5 ± 1.1 3 | 8.7 ± 1.3 3 | +1.2 ± 1.1 3 | NI | NI | NI | NI | NI | NI |
Control | 6.5 ± 0.7 3 | 5.3 ± 0.7 3 | −1.2 ± 0.6 3 | ||||||||
Zoungas et al. [52] b | 2004 | Intervention | NI | NI | NI | NI | 11.0 ± 3.714,17,22 10.2 ± 3.114,17,23 10.5 ± 1.8 14,22,24 10.2 ± 2.014,23,24 | NI | NI | 21.4 ± 11.6 14,22 25.2 ± 11.5 14,23 | NI |
Control | 9.4 ± 1.8 14,17,22 8.6 ± 1.7 14,17,23 10.8 ± 1.5 14,22,24 10.2 ± 1.6 14,23,24 | 12.0 ± 9.3 14,22 20.4 ± 9.9 14,23 | |||||||||
Doshi et al. [43] *,25 | 2003 | Intervention | 52 ± 34 14,16 | 110 ± 43 14,16 | NI | NI | NI | NI | NI | NI | NI |
Control | 46 ± 33 14,16 | 47 ± 35 14,16 | |||||||||
Doshi et al. [44] 26 | 2002 | Intervention | 52.5 ± 29 14,16 | 111 ± 28 14,16 | NI | NI | NI | NI | NI | NI | NI |
Control | 48 ± 24 14,16 | 52 ± 19 14,16 | |||||||||
Mangoni et al. [45] | 2002 | Intervention | NI | NI | NI | 8.4 ± 0.3 3,20 | 7.8 ± 0.4 3,20 | NI | NI | NI | NI |
Control | 8.3 ± 0.5 3,20 | 7.8 ± 0.3 3,20 | |||||||||
Doshi et al. [46] | 2001 | Intervention | 52 ± 34 14,16 | 110 ± 43 14,16 | NI | NI | NI | NI | NI | NI | NI |
Control | 46 ± 33 14,16 | 47 ± 35 14,16 | |||||||||
Miner et al. [60] | 2001 | Intervention 27 | 2.9 ± 6.7 14 | 6.9 ± 6.3 14 | 4.0 ± 7.6 14 | NI | NI | NI | NI | NI | NI |
Intervention 1 | 5.9 ± 8.3 14 | 3.1 ± 4.8 14 | −5.1 ± 8.6 14 | ||||||||
Control | 7.1 ± 5.9 14 | 2.0 ± 7.7 14 | −2.8 ± 9.2 14 | ||||||||
Pullin et al. [47] | 2001 | Intervention 1 | 98 ± 73 14,16 | 114 ± 59 14,16 | NI | NI | NI | NI | NI | NI | NI |
Intervention 28 | 110 ± 67 14,16 | ||||||||||
Control | 118 ± 68 14,16 | ||||||||||
Thambyrajah et al. [48] | 2001 | Intervention | 3.3 (2.2–4.3) 18 | 4.5 (3.5–5.4) 18 | 1.2 (0.7–1.8) 18 | NI | NI | NI | NI | NI | NI |
Control | 3.8 (2.6–4.9) 18 | 4.1 (3.2–5.1) 18 | 0.4 (–0.3–1.1) 18 | ||||||||
Thambyrajah et al. [49] | 2000 | Intervention | 3.7 (2.8–4.6) 18 | 4.3 (3.5–5.2) 18 | NI | NI | NI | NI | NI | NI | NI |
Control | 2.6 (1.7–3.5) 18 | 3.9 (2.9–5.0) 18 | |||||||||
Title et al. [59] | 2000 | Intervention 1 | 3.2 ± 3.6 14 | 5.2 ± 3.9 14 | NI | NI | NI | NI | NI | NI | NI |
Intervention 29 | 2.6 ± 2.4 14 | 4.0 ± 3.7 14 | |||||||||
Control | 2.7 ± 3.3 14 | 2.9 ± 3.7 14 | |||||||||
Wilmink et al. [55] | 2000 | Intervention | 9.6 (7.1–12.8) 6 | 9.9 (7.5–14.1) 6 | NI | NI | NI | NI | NI | NI | NI |
Control | 10.6 (8.3–12.2) 6 | 5.8 (3.0–10.2) 6 | |||||||||
Bellamy et al. [37] | 1999 | Intervention | 24 ± 17 3,30 | 21 ± 14 3,30 | +50 ± 30 3,30 | NI | NI | NI | NI | NI | NI |
Control | 26 ± 21 3,30 | +60 ± 53 3,30 | |||||||||
Woo et al. [38] | 1999 | Intervention | 5.7 ± 1.2 14 | 8.2 ± 1.6 14 | NI | NI | NI | NI | NI | NI | NI |
Control | 6.0 ± 1.3 14 |
Author | Year | Group | ADMA (μmol/L) | sVCAM-1 (ng/mL) | ICAM-1 (ng/mL) | MCP-1 (pg/mL) | PAI-1 (ng/L) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Pre | Post | Changes (%) | Pre | Post | Changes (%) | Pre | Post | Changes (%) | Pre | Post | Changes (%) | Pre | Post | Changes (%) | |||
Li et al. [39] | 2020 | Intervention 1 | NI | NI | NI | NI | NI | NI | NI | NI | NI | 316.64 ± 97.65 4 | 230.63 ± 61.81 4 | −86.02 ± 87.30 4 | NI | NI | NI |
Intervention 2 | 327.39 ± 116.91 4 | 251.38 ± 88.90 4 | −76.01 ± 96.99 4 | NI | NI | NI | |||||||||||
Intervention 3 | 311.01 ± 83.49 4 | 242.02 ± 87.39 4 | −68.99 ± 77.34 4 | NI | NI | NI | |||||||||||
Control | 310.97 ± 115.78 4 | 306.04 ± 82.41 4 | −4.94 ± 126.34 4 | NI | NI | NI | |||||||||||
Ma et al. [61] | 2019 | Intervention 1 | NI | NI | NI | NI | NI | NI | NI | NI | NI | 802.27 ± 6.74 4 | 783.76 ± 3.45 4 | NI | NI | NI | NI |
Intervention 5 | 805.99 ± 3.65 4 | 796.32 ± 3.59 4 | NI | NI | NI | ||||||||||||
Intervention 6 | 804.97 ± 6.24 4 | 747.18 ± 3.83 4 | NI | NI | NI | ||||||||||||
Control | 798.77 ± 7.66 4 | 796.44 ± 7.50 4 | NI | NI | NI | ||||||||||||
Austen et al. [28] | 2006 | Intervention | 0.41 ± 0.25 4 | 0.33 ± 0.08 4 | –19.8 ± 17.6 4 | NI | NI | NI | NI | NI | NI | NI | NI | NI | NI | NI | NI |
Control | 0.58 ± 0.23 4 | 0.48 ± 0.25 4 | +8.2 ± 70.3 4 | NI | NI | NI | |||||||||||
Solini et al. [62] | 2006 | Intervention | NI | NI | NI | NI | NI | NI | NI | NI | NI | 290 ± 85 4 | 247 ± 86 4 | NI | NI | NI | NI |
Control | 304 ± 71 4 | 316 ± 73 4 | NI | NI | NI | ||||||||||||
Spoelstra-de Man et al. [56] a | 2006 | Intervention | 0.50 ± 0.08 4 | 0.5 (0.44–0.55) 7,8 | −0.7 9 | NI | NI | NI | NI | NI | NI | NI | NI | NI | NI | NI | NI |
Control | 0.50 ± 0.07 4 | 0.49 (0.42–0.56) 7,8 | −0.2 9 | NI | NI | NI | |||||||||||
Title et al. [58] | 2006 | Intervention | NI | NI | NI | 568.5 (486.4–664.5) 10 | 557.8 (465.9–671.2) 10 | NI | 241.5 (222.5–262.2) 10 | 230.2 (212.5–249.4)10 | NI | NI | NI | NI | NI | NI | NI |
Control | 544.6 (462.2–641.6) 10 | 543.5 (457.6–645.5) 10 | 230.9 (214.4–248.6) 10 | 226.8 (212.3–242.3) 10 | NI | NI | NI | ||||||||||
Durga et al. [57] | 2005 | Intervention | NI | NI | NI | NI | NI | NI | 139 (118–160) 7 | 139 (119–161) 7 | NI | NI | NI | NI | NI | NI | NI |
Control | 139 (114–165) 7 | 139 (118–170) 7 | NI | ||||||||||||||
Spoelstra-de Man et al. [54] a | 2004 | Intervention | NI | NI | NI | 1347 (1070–1640) 7 | NI | −1 (−33–25) 11 | 668 (598–865) 7 | NI | 0 (−45–64) 11 | NI | NI | NI | NI | NI | NI |
Control | 1399 (1078–1576) 7 | −1 (−41–79) 11 | 797 (513–1046) 7 | 2 (−29–71) 11 | NI | NI | NI | ||||||||||
Kunz et al. [36] | 1999 | Intervention | NI | NI | NI | NI | NI | NI | NI | NI | NI | NI | NI | NI | 13.5 ± 13.5 4 | 10.9 ± 4.3 4 | NI |
Control | 14.5 ± 11.5 4 | 17.8 ± 12.9 4 | NI |
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Bokayeva, K.; Jamka, M.; Banaszak, M.; Makarewicz-Bukowska, A.; Adamczak, A.; Chrobot, M.; Janicka, A.; Jaworska, N.; Walkowiak, J. The Effect of Folic Acid Supplementation on Endothelial Function and Arterial Stiffness Markers in Adults: A Systematic Review and Meta-Analysis. Healthcare 2023, 11, 2524. https://doi.org/10.3390/healthcare11182524
Bokayeva K, Jamka M, Banaszak M, Makarewicz-Bukowska A, Adamczak A, Chrobot M, Janicka A, Jaworska N, Walkowiak J. The Effect of Folic Acid Supplementation on Endothelial Function and Arterial Stiffness Markers in Adults: A Systematic Review and Meta-Analysis. Healthcare. 2023; 11(18):2524. https://doi.org/10.3390/healthcare11182524
Chicago/Turabian StyleBokayeva, Kamila, Małgorzata Jamka, Michalina Banaszak, Aleksandra Makarewicz-Bukowska, Ada Adamczak, Maria Chrobot, Adrianna Janicka, Natalia Jaworska, and Jarosław Walkowiak. 2023. "The Effect of Folic Acid Supplementation on Endothelial Function and Arterial Stiffness Markers in Adults: A Systematic Review and Meta-Analysis" Healthcare 11, no. 18: 2524. https://doi.org/10.3390/healthcare11182524