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1.
Effect of micronutrient supplements on influenza and other respiratory tract infections among adults: a systematic review and meta-analysis.
Abioye, AI, Bromage, S, Fawzi, W
BMJ global health. 2021;(1)
Abstract
Acute respiratory tract infections (ARIs) are a leading cause of ill-health and death globally. Individual or multiple micronutrients have been shown to modulate immune function and affect the risk and severity of a number of infectious diseases. We systematically reviewed the evidence on the impact of micronutrient supplements to reduce the occurrence of ARIs and shorten the duration of ARI symptoms among adults. Random effects meta-analyses were conducted to estimate the pooled effects of vitamin D, vitamin C, zinc and multiple micronutrient supplementation (MMS) on the occurrence of ARIs and the duration of ARI symptoms. Vitamin D supplementation reduced the risk of ARI (risk ratio (RR)=0.97; 95% CI 0.94 to 1.00; p=0.028) and shortened the duration of symptoms (per cent difference: -6% (95% CI -9% to -2%; p=0.003)). The RR of vitamin D to prevent ARI was farther from the null when diagnosis was based on clinical diagnosis or laboratory testing, compared with self-report and when the loading dose was <60 000 IU. Vitamin C supplementation reduced the risk of ARIs (RR=0.96; 95% CI 0.93 to 0.99; p=0.01) and shortened the duration of symptoms (per cent difference: -9% (95% CI -16% to -2%; p=0.014)). The effect of vitamin C on preventing ARI was stronger among men and in middle-income countries, compared with women and high-income countries, respectively. Zinc supplementation did not reduce the risk of ARIs but shortened the duration of symptoms substantially (per cent difference: -47% (95% CI -73% to -21%; p=0.0004)). Our synthesis of global evidence from randomised controlled trials indicates that micronutrient supplements including zinc, vitamins C and D, and multiple micronutrient supplements may be modestly effective in preventing ARIs and improving their clinical course. Further research is warranted to better understand the effectiveness that individual or multiple micronutrients have on SARS-CoV-2 infection and treatment outcomes.
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Antioxidant micronutrient supplementation in critically ill adults: A systematic review with meta-analysis and trial sequential analysis.
Gudivada, KK, Kumar, A, Shariff, M, Sampath, S, Varma, MM, Sivakoti, S, Krishna, B
Clinical nutrition (Edinburgh, Scotland). 2021;(3):740-750
Abstract
BACKGROUND The role of antioxidant micronutrient (AxM) supplementation in the critically ill patients has been controversial, and recent trials have suggested a tendency to harm. Therefore, we performed a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials (RCT) to examine the effect of AxM supplementation on clinical outcomes among critically ill adults. METHODS PubMed, EMBASE, Cochrane, CINAHL, LILACS, DARE, SCOPUS, and Web of sciences databases were searched from inception to March 2019. RCTs that compared AxM supplements with placebo in adult critically ill patients and reporting mortality as an outcomes were included. Trial quality was assessed using updated cochrane risk of bias (RoB-II) tool. Primary outcome was all-cause mortality. Secondary outcomes were 28-day mortality, intensive care unit (ICU) and hospital length of stay (LOS), ventilator days and infection between the two groups. Outcomes were summarised using random-effects estimators. Quality of evidence (QOE) was rated using Grading of Recommendations, Assessment, Development and Evaluation. Prior to final analysis, we repeated the search through September 2019. R version 3.6.2 and STATA version 13 were used for all statistical analyses. RESULTS Pooled analysis of 34 trials with 4678 patients revealed that AxM supplementation was associated with possible reduction in all-cause mortality (relative risk [RR], 0.89 [95%CI 0.79 to 0.99], TSA adjusted CI 0.77 to 1.03; Low QOE). Fragility index and number needed to treat were 1 and 41, respectively. Eight studies with low RoB (RR, 1.08; 95%CI 0.95 to 1.23; TSA CI, 0.64 to 1.82; moderate QOE) did not show mortality reduction with AxM supplementation. SECONDARY OUTCOMES ICU LOS (weighted mean difference [WMD], -0.84; 95%CI -1.50 to -0.18; moderate QOE), hospitalization days (WMD, -2.83; 95%CI -3.91to -1.75; low QOE) and ventilator days (WMD, -1.87; 95%CI -3.60 to -0.14; very low QOE) showed a statistically significant benefit with AxM supplementation. In meta-regression analysis, neither the duration of AxM therapy nor the dosage of selenium, which was the most widely studied AxM, reported an association with mortality. CONCLUSION Although AxM supplementation was associated with possible reduction in all-cause mortality, results from the TSA and studies with low RoB showing null effect suggest that the evidence of benefit is questionable. Secondary outcomes attained statistically significant benefit with AxM supplements, but the certainity of evidence was low. To summarize, current evidence does not justify administration of AxM in critically ill patients. REGISTRATION PROSPERO, CRD42019125898.
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Breakfast Characteristics and Its Association with Daily Micronutrients Intake in Children and Adolescents-A Systematic Review and Meta-Analysis.
Giménez-Legarre, N, Miguel-Berges, ML, Flores-Barrantes, P, Santaliestra-Pasías, AM, Moreno, LA
Nutrients. 2020;(10)
Abstract
Breakfast is an important source of key nutrients in the diet. For this reason, the aim of this review was to investigate the associations between breakfast consumption and daily micronutrients intake in both children and adolescents (aged 2-18 years). A peer-reviewed systematic search was conducted in three datasets (PubMed, Scopus and Cochrane Library) in February 2020 in English and Spanish. Two independent reviewers evaluated 3188 studies considering the AXIS critical appraisal and PRISMA methodologies. Meta-analysis was carried out comparing results according to type of breakfast consumed (Ready to eat cereals (RTEC) breakfast or other types of breakfast) and breakfast skipping. Thirty-three articles were included in the systematic review (SR) and 7 in the meta-analysis. In the SR, we observed that those children and adolescents who usually consume RTEC at breakfast had a higher consumption of B-vitamins than those not consuming RTEC at breakfast. Breakfast consumers had a higher mineral intake (iron, calcium, magnesium, potassium, zinc, and iodine) than breakfast skippers. In the Meta-Analysis, RTEC consumers had significantly higher vitamin C intake than breakfast skippers (SMD, -4.12; 95% confidence intervals (CI): -5.09, -3.16). Furthermore, those children who usually consume breakfast had significantly higher daily intake of calcium than breakfast skippers (SMD, -7.03; 95%CI: -9.02, -5.04). Our review proposes that breakfast consumption seems to be associated with higher daily micronutrients intake than breakfast skippers.
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Effects of Dietary or Supplementary Micronutrients on Sex Hormones and IGF-1 in Middle and Older Age: A Systematic Review and Meta-Analysis.
Janjuha, R, Bunn, D, Hayhoe, R, Hooper, L, Abdelhamid, A, Mahmood, S, Hayden-Case, J, Appleyard, W, Morris, S, Welch, A
Nutrients. 2020;(5)
Abstract
Observational research suggests that micronutrients may be protective for sarcopenia, a key health issue during ageing, potentially via effects on hormone synthesis and metabolism. We aimed to carry out a systematic review of RCTs investigating effects of increasing dietary or supplemental micronutrient intake on sex hormones and IGF-1 in individuals aged 45 years or older. We searched MEDLINE, EMBASE and Cochrane databases for RCTs reporting the effects of different micronutrients (vitamins A, C, D, or E; carotenoids; iron; copper; zinc; magnesium; selenium; and potassium) on sex hormones or IGF-1. Of the 26 RCTs identified, nine examined effects of vitamin D, nine of multi-nutrients, four of carotenoids, two of selenium, one of zinc, and one of vitamin E. For IGF-1 increasing vitamin D (MD: -0.53 nmol/L, 95% CI: -1.58, 0.52), multi-nutrients (MD: 0.60 nmol/L, 95% CI -1.12 to 2.33) and carotenoids (MD -1.32 nmol/L; 95% CI -2.76 to 0.11) had no significant effect on circulating concentrations. No significant effects on sex hormones of other micronutrients were found, but data were very limited. All trials had significant methodological limitations making effects of micronutrient supplementation on sex hormones unclear. Further high quality RCTs with physiological doses of micronutrients in people with low baseline intakes or circulating concentrations, using robust methodology, are required to assess effects of supplementation adequately.
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Effectiveness of micronutrients supplement in patients with active tuberculosis on treatment: Systematic review/Meta-analysis.
Cabrera Andrade, BK, Garcia-Perdomo, HA
Complementary therapies in medicine. 2020;:102268
Abstract
BACKGROUND Multiple researchers have suggested the influence of micronutrients in the cure and survival of tuberculosis. OBJECTIVE To determine the effectiveness of micronutrients in the cure and treatment of pulmonary tuberculosis. METHODS Systematic search of randomized controlled trials (RCTs) in databases of people under treatment for active pulmonary tuberculosis, that must have received oral micronutrients for at least four weeks compared with placebo. The synthesis of the variables was shown in standardized mean difference (MD) and/or risk difference (RD). The random effects model was used and was reported in forest plot of the estimates of the effect with a 95 % CI. RESULTS Sixteen of 246 studies were included, in total 4398 people. Zinc showed (RD, 0.04; 95 % CI, 0.00-0.08) in mortality, increases muscle mass index (MD, 1.20; 95 % CI, 0.04-2.36) and gains weight (MD, 3.10; 95 % CI, 0.66-5.54). Zinc plus vitamin A increases the weight (MD, 3.10; 95 % CI, 2.78-3.42), improving karnofsky scale (MD, 2.50; 95 % CI, 2.22-2.78). Additionally, vitamin D accelerate the sputum conversión time (RD, 0.38; 95 % CI, 0.03-0.73). Hemoglobin (Hb) with vitamin A and zinc achieves statistically significant changes (MD, 0.69; 95 % CI, 0.28-1.09) and (MD, 0.52; 95 % CI, 0.21-0.83) and reduces area of cavitations in chest X-ray (MD, -0.33; 95 % CI, -0.60--0.06). CONCLUSIONS The consumption of micronutrients could achieve weight gain, hemoglobin, accelerated sputum conversion and improvement in quality of life. There are no changes in mortality that may be attributable to the suboptimal dose, larger studies are suggested with adequate doses.
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6.
Food fortification with multiple micronutrients: impact on health outcomes in general population.
Das, JK, Salam, RA, Mahmood, SB, Moin, A, Kumar, R, Mukhtar, K, Lassi, ZS, Bhutta, ZA
The Cochrane database of systematic reviews. 2019;(12):CD011400
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Abstract
BACKGROUND Vitamins and minerals are essential for growth and maintenance of a healthy body, and have a role in the functioning of almost every organ. Multiple interventions have been designed to improve micronutrient deficiency, and food fortification is one of them. OBJECTIVES To assess the impact of food fortification with multiple micronutrients on health outcomes in the general population, including men, women and children. SEARCH METHODS We searched electronic databases up to 29 August 2018, including the Cochrane Central Register of Controlled Trial (CENTRAL), the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register and Cochrane Public Health Specialised Register; MEDLINE; Embase, and 20 other databases, including clinical trial registries. There were no date or language restrictions. We checked reference lists of included studies and relevant systematic reviews for additional papers to be considered for inclusion. SELECTION CRITERIA We included randomised controlled trials (RCTs), cluster-RCTs, quasi-randomised trials, controlled before-after (CBA) studies and interrupted time series (ITS) studies that assessed the impact of food fortification with multiple micronutrients (MMNs). Primary outcomes included anaemia, micronutrient deficiencies, anthropometric measures, morbidity, all-cause mortality and cause-specific mortality. Secondary outcomes included potential adverse outcomes, serum concentration of specific micronutrients, serum haemoglobin levels and neurodevelopmental and cognitive outcomes. We included food fortification studies from both high-income and low- and middle-income countries (LMICs). DATA COLLECTION AND ANALYSIS Two review authors independently screened, extracted and quality-appraised the data from eligible studies. We carried out statistical analysis using Review Manager 5 software. We used random-effects meta-analysis for combining data, as the characteristics of study participants and interventions differed significantly. We set out the main findings of the review in 'Summary of findings' tables, using the GRADE approach. MAIN RESULTS We identified 127 studies as relevant through title/abstract screening, and included 43 studies (48 papers) with 19,585 participants (17,878 children) in the review. All the included studies except three compared MMN fortification with placebo/no intervention. Two studies compared MMN fortification versus iodised salt and one study compared MMN fortification versus calcium fortification alone. Thirty-six studies targeted children; 20 studies were conducted in LMICs. Food vehicles used included staple foods, such as rice and flour; dairy products, including milk and yogurt; non-dairy beverages; biscuits; spreads; and salt. Fourteen of the studies were fully commercially funded, 13 had partial-commercial funding, 14 had non-commercial funding and two studies did not specify the source of funding. We rated all the evidence as of low to very low quality due to study limitations, imprecision, high heterogeneity and small sample size. When compared with placebo/no intervention, MMN fortification may reduce anaemia by 32% (risk ratio (RR) 0.68, 95% confidence interval (CI) 0.56 to 0.84; 11 studies, 3746 participants; low-quality evidence), iron deficiency anaemia by 72% (RR 0.28, 95% CI 0.19 to 0.39; 6 studies, 2189 participants; low-quality evidence), iron deficiency by 56% (RR 0.44, 95% CI 0.32 to 0.60; 11 studies, 3289 participants; low-quality evidence); vitamin A deficiency by 58% (RR 0.42, 95% CI 0.28 to 0.62; 6 studies, 1482 participants; low-quality evidence), vitamin B2 deficiency by 64% (RR 0.36, 95% CI 0.19 to 0.68; 1 study, 296 participants; low-quality evidence), vitamin B6 deficiency by 91% (RR 0.09, 95% CI 0.02 to 0.38; 2 studies, 301 participants; low-quality evidence), vitamin B12 deficiency by 58% (RR 0.42, 95% CI 0.25 to 0.71; 3 studies, 728 participants; low-quality evidence), weight-for-age z-scores (WAZ) (mean difference (MD) 0.1, 95% CI 0.02 to 0.17; 8 studies, 2889 participants; low-quality evidence) and weight-for-height/length z-score (WHZ/WLZ) (MD 0.1, 95% CI 0.02 to 0.18; 6 studies, 1758 participants; low-quality evidence). We are uncertain about the effect of MMN fortification on zinc deficiency (RR 0.84, 95% CI 0.65 to 1.08; 5 studies, 1490 participants; low-quality evidence) and height/length-for-age z-score (HAZ/LAZ) (MD 0.09, 95% CI 0.01 to 0.18; 8 studies, 2889 participants; low-quality evidence). Most of the studies in this comparison were conducted in children. Subgroup analyses of funding sources (commercial versus non-commercial) and duration of intervention did not demonstrate any difference in effects, although this was a relatively small number of studies and the possible association between commercial funding and increased effect estimates has been demonstrated in the wider health literature. We could not conduct subgroup analysis by food vehicle and funding; since there were too few studies in each subgroup to draw any meaningful conclusions. When we compared MMNs versus iodised salt, we are uncertain about the effect of MMN fortification on anaemia (R 0.86, 95% CI 0.37 to 2.01; 1 study, 88 participants; very low-quality evidence), iron deficiency anaemia (RR 0.40, 95% CI 0.09 to 1.83; 2 studies, 245 participants; very low-quality evidence), iron deficiency (RR 0.98, 95% CI 0.82 to 1.17; 1 study, 88 participants; very low-quality evidence) and vitamin A deficiency (RR 0.19, 95% CI 0.07 to 0.55; 2 studies, 363 participants; very low-quality evidence). Both of the studies were conducted in children. Only one study conducted in children compared MMN fortification versus calcium fortification. None of the primary outcomes were reported in the study. None of the included studies reported on morbidity, adverse events, all-cause or cause-specific mortality. AUTHORS' CONCLUSIONS The evidence from this review suggests that MMN fortification when compared to placebo/no intervention may reduce anaemia, iron deficiency anaemia and micronutrient deficiencies (iron, vitamin A, vitamin B2 and vitamin B6). We are uncertain of the effect of MMN fortification on anthropometric measures (HAZ/LAZ, WAZ and WHZ/WLZ). There are no data to suggest possible adverse effects of MMN fortification, and we could not draw reliable conclusions from various subgroup analyses due to a limited number of studies in each subgroup. We remain cautious about the level of commercial funding in this field, and the possibility that this may be associated with higher effect estimates, although subgroup analysis in this review did not demonstrate any impact of commercial funding. These findings are subject to study limitations, imprecision, high heterogeneity and small sample sizes, and we rated most of the evidence low to very low quality. and hence no concrete conclusions could be drawn from the findings of this review.
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Micronutrient Intake and Risk of Hematological Malignancies in Adults: A Systematic Review and Meta-analysis of Cohort Studies.
Psaltopoulou, T, Ntanasis-Stathopoulos, I, Tsilimigras, DI, Tzanninis, IG, Gavriatopoulou, M, Sergentanis, TN
Nutrition and cancer. 2018;(6):821-839
Abstract
There has been accumulating evidence that several micronutrients may play a protective role in the risk of solid cancers. However, their role in hematological malignancies remains to be elucidated; this meta-analysis aims to evaluate the associations between micronutrient intake as well as supplementation and risk of hematological cancer in adults. Eligible cohort studies (examining intake of vitamin A, vitamin C, vitamin D, vitamin E, lycopene, folate, iron, carotenoids, beta-carotene, selenium, pyridoxine) were sought in PubMed up to July 31, 2016. Random-effects models were used for the calculation of pooled relative risks (RR) with their 95% confidence intervals (CI). Twelve cohort studies were deemed eligible. Null associations were noted regarding supplemented vitamin A (pooled relative risk [RR] = 0.92, 95% confidence interval [CI]: 0.80-1.07), supplemented vitamin C (pooled RR = 1.00, 95%CI: 0.90-1.12), total vitamin D (pooled RR = 1.05, 95%CI: 0.91-1.20), supplemented vitamin E (pooled RR = 0.98, 95%CI: 0.88-1.10), and dietary lycopene intake (pooled RR = 1.00, 95%CI: 0.86-1.16) and the risk of non-Hodgkin lymphoma. No summary estimates are provided for other hematological malignancies due to the limited number of studies. Future prospective trials should be conducted for a better understanding of this field; especially regarding Hodgkin lymphoma, leukemia and plasma cell neoplasms, on which data are scarce.
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Feeding the brain - The effects of micronutrient interventions on cognitive performance among school-aged children: A systematic review of randomized controlled trials.
Lam, LF, Lawlis, TR
Clinical nutrition (Edinburgh, Scotland). 2017;(4):1007-1014
Abstract
BACKGROUND & AIMS Micronutrients are essential for brain development with deficiencies in specific nutrients linked to impaired cognitive function. Interventions are shown to be beneficial to children's mental development, particularly in subjects who were micronutrient-deficient at baseline but results on healthy subjects remain inconsistent. This systematic review evaluated the effect of micronutrient inventions on different cognitive domains. Studies conducted in both developing and developed countries, and trials that investigate the effect of both single and multiple micronutrient intervention were reviewed. METHODS Systematic searches of Medline, CINAHL Plus and Academic Search database were undertaken to identify trials published after year 2000. Randomized controlled trials (RCTs) that evaluate the effect of micronutrients on cognitive performance or academic performance among children aged 4-18 years were included. RESULTS 19 trials were identified from 18 articles. The major cognitive outcomes assessed included fluid intelligence, crystallized intelligence, short-term memory, long-term memory, cognitive processing speed, attention and concentration, and school performance. Eight of ten trials assessing fluid intelligence reported significant positive effects of micronutrient supplementation among micronutrient-deficient children, especially those who were iron-deficient or iodine-deficient at baseline. The effects of micronutrient interventions on other domains were inconsistent. CONCLUSION Improvement in fluid intelligence among micronutrient-deficient children was consistently reported. Further research is needed to provide more definite evidence on the beneficial effects of micronutrient inventions on other cognitive domains and the effects in healthy subjects.
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Modifiers of the effect of maternal multiple micronutrient supplementation on stillbirth, birth outcomes, and infant mortality: a meta-analysis of individual patient data from 17 randomised trials in low-income and middle-income countries.
Smith, ER, Shankar, AH, Wu, LS, Aboud, S, Adu-Afarwuah, S, Ali, H, Agustina, R, Arifeen, S, Ashorn, P, Bhutta, ZA, et al
The Lancet. Global health. 2017;(11):e1090-e1100
Abstract
BACKGROUND Micronutrient deficiencies are common among women in low-income and middle-income countries. Data from randomised trials suggest that maternal multiple micronutrient supplementation decreases the risk of low birthweight and potentially improves other infant health outcomes. However, heterogeneity across studies suggests influence from effect modifiers. We aimed to identify individual-level modifiers of the effect of multiple micronutrient supplements on stillbirth, birth outcomes, and infant mortality in low-income and middle-income countries. METHODS This two-stage meta-analysis of individual patient included data from 17 randomised controlled trials done in 14 low-income and middle-income countries, which compared multiple micronutrient supplements containing iron-folic acid versus iron-folic acid alone in 112 953 pregnant women. We generated study-specific estimates and pooled subgroup estimates using fixed-effects models and assessed heterogeneity between subgroups with the χ2 test for heterogeneity. We did sensitivity analyses using random-effects models, stratifying by iron-folic acid dose, and exploring individual study effect. FINDINGS Multiple micronutrient supplements containing iron-folic acid provided significantly greater reductions in neonatal mortality for female neonates compared with male neonates than did iron-folic acid supplementation alone (RR 0·85, 95% CI 0·75-0·96 vs 1·06, 0·95-1·17; p value for interaction 0·007). Multiple micronutrient supplements resulted in greater reductions in low birthweight (RR 0·81, 95% CI 0·74-0·89; p value for interaction 0·049), small-for-gestational-age births (0·92, 0·87-0·97; p=0·03), and 6-month mortality (0·71, 0·60-0·86; p=0·04) in anaemic pregnant women (haemoglobin <110g/L) as compared with non-anaemic pregnant women. Multiple micronutrient supplements also had a greater effect on preterm births among underweight pregnant women (BMI <18·5 kg/m2; RR 0·84, 95% CI 0·78-0·91; p=0·01). Initiation of multiple micronutrient supplements before 20 weeks gestation provided greater reductions in preterm birth (RR 0·89, 95% CI 0·85-0·93; p=0·03). Generally, the survival and birth outcome effects of multiple micronutrient supplementation were greater with high adherence (≥95%) to supplementation. Multiple micronutrient supplements did not significantly increase the risk of stillbirth or neonatal, 6-month, or infant mortality, neither overall or in any of the 26 examined subgroups. INTERPRETATION Antenatal multiple micronutrient supplements improved survival for female neonates and provided greater birth-outcome benefits for infants born to undernourished and anaemic pregnant women. Early initiation in pregnancy and high adherence to multiple micronutrient supplements also provided greater overall benefits. Studies should now aim to elucidate the mechanisms accounting for differences in the effect of antenatal multiple micronutrient supplements on infant health by maternal nutrition status and sex. FUNDING None.
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Effects of individual micronutrients on blood pressure in patients with type 2 diabetes: a systematic review and meta-analysis of randomized clinical trials.
de Paula, TP, Kramer, CK, Viana, LV, Azevedo, MJ
Scientific reports. 2017;:40751
Abstract
To investigate the effects of micronutrients on blood pressure (BP) in patients with type 2 diabetes through a systematic review and meta-analysis, randomized clinical trials (RCTs) of the effects of individual micronutrients on BP in patients with type 2 diabetes were searched in the Medline, Embase, Cochrane, and Clinical Trials.gov databases through April 2016. From the 28,164 studies, 11 RCTs (13 interventions, 723 patients, 54% males) with 3 to 52 weeks of follow-up were classified according to the type of micronutrient intervention: sodium (n = 1), vitamin C (n = 2), vitamin D (n = 7), and magnesium (n = 1). The available data enabled us to perform meta-analyses of vitamins C and D. Vitamin C reduced diastolic BP [WMD -2.88 mmHg (95%CI -5.31, -0.46; P = 0.020)] but not systolic BP [WMD -3.93 mmHg (95%CI -14.78, 6.92; P = 0.478)]. Vitamin D caused a reduction of 4.56 mmHg (WMD; 95%CI -7.65, -1.47; P = 0.004) for systolic BP and 2.44 mm Hg (WMD; 95%CI -3.49, -1.39; P < 0.001) for diastolic BP. In conclusion, vitamin D and possibly vitamin C have beneficial effects on BP in patients with type 2 diabetes. These interventions might represent a novel approach to the treatment of hypertension in these patients.