The effect of vitamin D supplementation on cardiovascular risk in patients with prediabetes: A secondary analysis of the D2d study

AimsLow blood 25(OH)D level is associated with increased cardiovascular disease (CVD) risk. Additionally, individuals with prediabetes are at higher risk for CVD than individuals with normoglycemia. We investigated the effects of vitamin D supplementation on CVD outcomes in the vitamin D and type 2 diabetes (D2d) study, a large trial among adults with prediabetes.Methods2423 participants were randomized to 4000 IU/day of vitamin D₃ or placebo and followed for median 3.0 years for new-onset diabetes. In pre-specified secondary analyses, we examined the effect of vitamin D supplementation on composite Major Adverse Cardiovascular Events (MACE); expanded MACE (MACE + revascularization); atherosclerotic CVD (ASCVD) risk score; and individual CVD risk factors (blood pressure, lipids, high-sensitivity C-reactive protein). Cox models compared hazard ratios (HR) between the two groups on MACE and expanded MACE.ResultsMean age was 60 years, 45 % were women, 13 % had history of CVD. Twenty-one participants assigned to vitamin D and 12 participants assigned to placebo met the MACE outcome (HR 1.81, 95%CI 0.89 to 3.69). There were 27 expanded MACE outcomes in each group (HR 1.02, 95%CI, 0.59 to 1.76). There were no significant differences between vitamin D and placebo in individual CVD risk factors, but change in ASCVD risk score favored the vitamin D group (?0.45 %, 95%CI -0.75 to ?0.15).ConclusionsIn people with prediabetes not selected for vitamin D insufficiency and with intermediate CVD risk, vitamin D supplementation did not decrease MACE but had a small favorable effect on ASCVD risk score.Trial registration: D2d ClinicalTrials.gov number, NCT01942694, prospectively registered September 16, 2013.     

Circulating vitamin C and the risk of cardiovascular diseases: A Mendelian randomization study

Background and aimsThe impact of vitamin C supplementation on the risk of cardiovascular diseases (CVDs) remains uncertain with inconsistent evidence obtained from observational studies and randomized clinical trials (RCTs). We aimed to assess possible causal associations of vitamin C with major CVD events as well as their risk factors using Mendelian randomization (MR) design.Methods and resultsNine genetic variants associated with vitamin C at genome-wide significance (p < 5 × 10^?8) were used as instrumental variables to predict plasma vitamin C levels. The primary outcomes were coronary artery disease (Ncase = 122,733 and Ncontrol = 424,528), atrial fibrillation (Ncase = 60,620 and Ncontrol = 970,216), heart failure (Ncase = 47,309 and Ncontrol = 930,014), and ischemic stroke (Ncase = 40,585 and Ncontrol = 406,111). Several CVD risk factors were also evaluated in secondary analyses. Two-sample MR analyses were performed using the inverse variance weighted method, with several sensitivity analyses. Genetically determined higher levels of plasma vitamin C were not significantly associated with any of the four examined CVD events. Likewise, there is no convincing evidence for the associations between genetically determined vitamin C and CVD risk factors, including higher blood lipids, higher blood pressure, and abnormal body composition. Sensitivity analyses using different analytical approaches yielded consistent results. Additionally, MR assumptions did not seem to be violated.ConclusionThis MR study does not support a causal protective role to circulate vitamin C levels on various types of CVD events. In combination with previous RCT results, our findings suggest that vitamin C supplementation to increase circulating vitamin C levels may not help in CVD prevention.     

Serum and dietary vitamin D and cardiovascular disease risk in elderly men: a prospective cohort study

Background and aimRecent research suggests that low vitamin D may be associated with cardiovascular disease (CVD).Methods and resultsWe prospectively evaluated the association of dietary plus supplemental vitamin D intake and serum 25(OH) vitamin D with CVD incidence in the Osteoporotic Fractures in Men (MrOS) Study. Vitamin D intake was measured using a food frequency questionnaire and self-reported supplemental intake in 3094 men (mean age 76.4 years). From a subset of this population, we measured 25(OH) vitamin D in 813 men. Median 25(OH) vitamin D was 25.3 ng/mL. During a median follow-up of 4.4 years, there were 472 CVD cases, including 371 from coronary heart disease (CHD) and 101 from cerebrovascular attack (CVA). In the 25(OH) vitamin D sub-cohort, there were 140 cases of CVD including 115 from CHD and 25 from CVA. We used a Cox proportional hazards regression to calculate hazard ratios (HR) for CVD by vitamin D quartile. After adjusting for age, season, and standard CVD risk factors, the lowest quartile of 25(OH) vitamin D (HR, 1.18; 95% CI, 0.69–2.03) and vitamin D intake (HR, 0.76; 95% CI, 0.56–1.04) were not significantly associated with CVD incidence, compared to the highest vitamin D quartiles. When 25(OH) vitamin D was further analyzed by sufficiency (≥30 ng/mL), insufficiency (≥15–29.9 ng/mL), and deficiency (<15 ng/mL), vitamin D deficiency was not significantly associated with CVD incidence compared to sufficiency (HR 1.34; 95% CI 0.65–2.77).ConclusionVitamin D intake and serum 25(OH) vitamin D were not associated with CVD risk.     

Vitamin D Deficiency and Its Implications on Cardiovascular Disease

Vitamin D is widely known for its important role in bone health. More recent evidence suggests that vitamin D may also play a protective role in many chronic conditions, including cancer, autoimmune, kidney, and cardiovascular diseases (CVDs). Observational studies have associated low vitamin D levels with CVD risk factors, including hypertension, hyperlipidemia, diabetes, and metabolic syndrome, as well as with cardiovascular events, including stroke, myocardial infarction, and congestive heart failure. Much less evidence is available from clinical trials of vitamin D supplementation. It remains to be determined whether the vitamin D–CVD relationship is causal, and what dosing of vitamin D supplementation would be adequate for prevention. Large-scale randomized controlled trials with adequate vitamin D dosing are needed before treatment strategies can be implemented. The purpose of this article is to review the scientific evidence linking vitamin D deficiency with CVD, including explanations of potential biologic mechanisms.     

Vitamin D and Cardiovascular Disease: Is There Evidence to Support the Bandwagon?

In the last 3?years, more evidence accumulated that vitamin D (vitD)deficiency associates with cardiovascular disease (CVD) and risk factors. The association with higher cardiovascular (CV) mortality was stronger than with nonfatal CVD events. A higher incidence of type 2 diabetes was also shown. Many factors related to lifestyle (physical activity in particular) influence both vitD levels and CVD, and may contribute to explain these observational data. Whether the association between vitD and CVD is causal can only be established through randomized controlled trials (RCTs), and to date the results of the randomized trials, which were not designed for investigating CV outcomes, do not support the association data. Answers on the effects of vitD supplementation on primary and secondary prevention of CV may be found in the specifically designed ongoing RCTs. In the mean time, low vitamin D levels should be regarded as a marker of unhealthy lifestyle, requiring a more aggressive attempt at modifying individual lifestyle.     

Prevention of colorectal cancer with vitamin D

Abstract

The fact that colorectal cancer (CRC) is the second leading cause of cancer mortality in the United States emphasizes the need for more effective preventive and therapeutic modalities. There is growing evidence that vitamin D may reduce the incidence of CRC. Results of epidemiologic, in vitro, in vivo animal and clinical studies suggest that a low serum vitamin D level may be a serious risk factor for CRC and a high serum vitamin D level may reduce the risk of CRC. On a molecular level, vitamin D suppresses CRC development and growth by affecting cell proliferation, differentiation, apoptosis, and angiogenesis. Vitamin D insufficiency and CRC are common in the elderly population. Vitamin D insufficiency is simple to screen for and treatable with vitamin D supplementation. Serum 25-hydroxyvitamin D (calcidiol) is the best measure of vitamin D status and should be checked routinely for individuals with risk factors for CRC. Maintaining serum concentrations of calcidiol above 32 ng/ml (80 nmol/l) in individuals whose serum calcidiol level is low may help prevent CRC as well as osteoporosis, fractures, infections, and cardiovascular disease. Daily calcidiol intake of 1000 International Units can increase serum vitamin D to sufficient levels in most elderly persons and, based on available data, may substantially lower the incidence of CRC with minimal risks.     

Vitamin D, cardiovascular disease and mortality

A poor vitamin D status, i.e. low serum levels of 25-hydroxyvitamin D [25(OH)D], is common in the general population. This finding is of concern not only because of the classic vitamin D effects on musculoskeletal outcomes, but also because expression of the vitamin D receptor (VDR) and vitamin D metabolizing enzymes in the heart and blood vessels suggests a role of vitamin D in the cardiovascular system. VDR-knockout mice suffer from cardiovascular disease (CVD), and various experimental studies suggest cardiovascular protection by vitamin D, including antiatherosclerotic, anti-inflammatory and direct cardio-protective actions, beneficial effects on classic cardiovascular risk factors as well as suppression of parathyroid hormone (PTH) levels. In epidemiological studies, low levels of 25(OH)D are associated with increased risk of CVD and mortality. Data from randomized controlled trials (RCTs) are sparse and have partially, but not consistently, shown some beneficial effects of vitamin D supplementation on cardiovascular risk factors (e.g. arterial hypertension). We have insufficient data on vitamin D effects on cardiovascular events, but meta-analyses of RCTs indicate that vitamin D may modestly reduce all-cause mortality. Despite accumulating data suggesting that a sufficient vitamin D status may protect against CVD, we still must wait for results of large-scale RCTs before raising general recommendations for vitamin D in the prevention and treatment of CVD. In current clinical practice, the overall risks and costs of vitamin D supplementation should be weighed against the potential adverse consequences of untreated vitamin D deficiency.     

Effect of one-anastomosis gastric bypass on cardiovascular risk factors in patients with vitamin D deficiency and morbid obesity: A secondary analysis

Background and aimsBariatric patients often suffer from vitamin D (VD) deficiency, and both, morbid obesity and VD deficiency, are related to an adverse effect on cardiovascular disease (CVD) risk. Therefore, we assessed the change of known CVD risk factors and its associations during the first 12 months following one-anastomosis gastric bypass (OAGB).Methods and resultsIn this secondary analysis, CVD risk factors, medical history and anthropometric data were assessed in fifty VD deficient (25-hydroxy-vitamin D (25(OH)D) <75 nmol/l) patients, recruited for a randomized controlled trial of VD supplementation. Based on previous results regarding bone-mass loss and the association between VD and CVD risk, the study population was divided into patients with 25(OH)D ≥50 nmol/l (adequate VD group; AVD) and into those <50 nmol/l (inadequate VD group; IVD) at 6 and 12 months (T6/12) postoperatively. In the whole cohort, substantial remission rates for hypertension (38%), diabetes (30%), and dyslipidaemia (41%) and a significant reduction in CVD risk factors were observed at T12. Changes of insulin resistance markers were associated with changes of total body fat mass (TBF%), 25(OH)D, and ferritin. Moreover, significant differences in insulin resistance markers between AVD and IVD became evident at T12.ConclusionThese findings show that OAGB leads to a significant reduction in CVD risk factors and amelioration of insulin resistance markers, which might be connected to reduced TBF%, change in 25(OH)D and ferritin levels, as an indicator for subclinical inflammation, and an adequate VD status.Registered at clinicaltrials.gov(Identifier: NCT02092376) and EudraCT (Identifier: 2013-003546-16).     

Can vitamin D deficiency cause diabetes and cardiovascular diseases? Present evidence and future perspectives

Several studies have shown that vitamin D may play a role in many biochemical mechanisms in addition to bone and calcium metabolism. Recently, vitamin D has sparked widespread interest because of its involvement in the homeostasis of the cardiovascular system. Hypovitaminosis D has been associated with obesity, related to trapping in adipose tissue due to its lipophilic structure. In addition, vitamin D deficiency is associated with increased risk of cardiovascular disease (CVD) and this may be due to the relationship between low vitamin D levels and obesity, diabetes mellitus, dyslipidaemia, endothelial dysfunction and hypertension. However, although vitamin D has been identified as a potentially important marker of CVD, the mechanisms through which it might modulate cardiovascular risk are not fully understood. Given this background, in this work we summarise clinical retrospective and prospective observational studies linking vitamin D levels with cardio-metabolic risk factors and vascular outcome. Moreover, we review various randomised controlled trials (RCTs) investigating the effects of vitamin D supplementation on surrogate markers of cardiovascular risk. Considering the high prevalence of hypovitaminosis D among patients with high cardiovascular risk, vitamin D replacement therapy in this population may be warranted; however, further RCTs are urgently needed to establish when to begin vitamin D therapy, as well as to determine the dose and route and duration of administration.     

Effect of vitamin D supplementation on endothelial function – An updated systematic review with meta-analysis and meta-regression

Background and aimsAtherogenesis and endothelial dysfunction contribute to cardiovascular risk and vitamin D has been implemented in endothelial repair. This systematic review, meta-analysis and meta-regression aims to establish the effect of vitamin D supplementation on endothelial function.Methods and ResultsTo conduct the systematic review we searched the Cochrane Library of Controlled Trials, PubMed, ProQuest and EMBASE for randomized controlled trials that investigated the effects of vitamin D supplementation on flow-mediated dilation (FMD%), pulse wave velocity (PWV), and central augmentation index (AIx). Meta-analysis was based on a random effects model and inverse-variance methods to calculate either mean difference (MD) or standardized mean difference (SMD) as effects sizes. This was followed by meta-regression investigating the effect of baseline vitamin D concentrations, vitamin D dosing and study duration. Risk of bias was assessed using the JADAD scale and funnel plots.We identified 1056 studies of which 26 studies met inclusion criteria for quantitative analysis. Forty-two percent of the 2808 participants had either deficient or insufficient levels of vitamin D. FMD% (MD 1.17% (95% CI −0.20, 2.54), p = 0.095), PWV (SMD −0.09 m/s (95% CI −0.24, 0.07), p = 0.275) and AIx (SMD 0.05% (95% CI −0.1, 0.19), p = 0.52) showed no improvement with vitamin D supplementation. Sub-analysis and meta-regression revealed a tendency for AIx and FMD% to increase as weekly vitamin doses increased; no other significant relationships were identified.ConclusionsVitamin D supplementation showed no improvement in endothelial function. More evidence is required before recommendations for management of endothelial dysfunction can be made.     

Effect of vitamin D supplementation on markers of cardiometabolic risk in children and adolescents: A meta-analysis of randomized clinical trials

Background and aimsAn increasing attention to the effect of vitamin D supplementation on cardiometabolic risk markers in children and adolescents has been gained recently. However, the results are inconsistent. Therefore, we conducted a meta-analysis to examine the effect of vitamin D supplementation on cardiometabolic risk markers in children and adolescents.Methods and resultsEligible randomized controlled trials (RCTs) were identified by searching PubMed, EMBASE and Web of Science. The results of this study are synthetized and reported in accordance with the PRISMA statement. GRADE system was used to assess the certainty of evidence. A total of 9 RCTs were identified and included in the meta-analysis. We found that vitamin D supplementation did not affect the changes of cardiometabolic risk markers including high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), body mass index (BMI), waist circumferences, systolic blood pressure (SDP) and diastolic blood pressure (DBP). However, vitamin D supplementation showed a beneficial effect on fasting glucose (MD, −1.54 mg/dl, 95% CI -2.98 to −0.10) and TG (MD, −24.76 mg/dl, 95% CI -37.66 to −11.86) in the sub-group analysis of total vitamin D supplementation ≥ 200,000 IU.ConclusionsVitamin D supplementation appeared to have a beneficial effect on reducing fasting glucose and TG level when total vitamin D supplementation ≥200,000 IU but not HDL-C, LDL-C TC, blood pressure and waist circumferences levels in children and adolescents. Further studies are needed to address this issue.     

Vitamin D as a therapy for colitis: A systematic review

Background and aimThe effect of vitamin D supplementation on immune disorders has been a topical research focus. The aim of this systematic review was to examine the current evidence of the effect of vitamin D supplementation as a therapy for colitis.MethodsThe following databases were searched: MEDLINE, Pubmed, Scopus, Web of Knowledge, Cinicaltrials.gov and the Cochrane Central Register of Controlled Trials using the terms ‘inflammatory bowel disease’ ‘Crohn's disease’ ‘ulcerative colitis’ ‘colitis’ [and] ‘vitamin D’. Both human and animal studies published in English language were examined. The reference lists of included studies and review articles were manually searched for any relevant studies.ResultsFour studies were included in this systematic review. All reported an improvement in disease activity with vitamin D supplementation. The only high quality human study reported a non-significant reduction of relapse rate for Crohn's disease. No major adverse effects of vitamin D supplementation were reported.ConclusionsAlthough there is some evidence that supplemental vitamin D, as an adjunctive treatment, may help in controlling colitis, this evidence is not enough to justify using vitamin D in treating inflammatory bowel disease (IBD). Large high quality placebo-controlled randomised controlled trials are needed to explore a possible benefit of using vitamin D in treating IBD.     

Vitamin D supplementation in pregnancy and early infancy in relation to gut microbiota composition and C. difficile colonization: implications for viral respiratory infections

ABSTRACT

In Canada and the US, the infant diet is supplemented with vitamin D via supplement drops or formula. Pregnant and nursing mothers often take vitamin D supplements. Since little is known about the impact of this supplementation on infant gut microbiota, we undertook a study to determine the association between maternal and infant vitamin D supplementation, infant gut microbiota composition and Clostridioides difficile colonization in 1,157 mother-infant pairs of the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study over 2009–2012. Logistic and MaAsLin regression were employed to assess associations between vitamin D supplementation, and C. difficile colonization, or other gut microbiota, respectively. Sixty-five percent of infants received a vitamin D supplement. Among all infants, infant vitamin D supplementation was associated with a lower abundance of genus Megamonas (q = 0.01) in gut microbiota. Among those exclusively breastfed, maternal prenatal supplementation was associated with lower abundance of Bilophila (q = 0.01) and of Lachnospiraceae (q = 0.02) but higher abundance of Haemophilus (q = 0.02). There were no differences in microbiota composition with vitamin D supplementation among partially and not breastfed infants. Neither infant nor maternal vitamin D supplementation were associated with C. difficile colonization, after adjusting for breastfeeding status and other factors. However, maternal consumption of vitamin-D fortified milk reduced the likelihood of C. difficile colonization in infants (adjustedOR: 0.40, 95% CI: 0.19–0.82). The impact of this compositional difference on later childhood health, especially defense against viral respiratory infection, may go beyond the expected effects of vitamin D supplements and remains to be ascertained.     

Vitamin D, thrombosis, and hemostasis: more than skin deep

Vitamin D(3) deficiency is a highly prevalent condition worldwide. Clinically, vitamin D(3) has a key role in calcium homeostasis and bone mineralization and has recently been implicated in the pathogenesis and/or progression of several acute and chronic illnesses, including cardiovascular disease (CVD). Accumulating evidence from observational, prospective studies suggests that low levels of serum 25-hydroxyvitamin D(3) are independently associated with an increased risk of CVD events and death. The molecular mechanisms of this association remain incompletely understood. A variety of biologically plausible mechanisms may mediate a cardiovascular role for the active metabolite of vitamin D(3). 1-α,25-dihydroxyvitamin D(3) regulates the renin-angiotensin system, suppresses proliferation of vascular cell smooth muscle, improves insulin resistance and endothelial cell-dependent vasodilation, inhibits myocardial cell hypertrophy, exerts anticoagulant and antifibrotic activity, and modulates macrophage activity and cytokine generation. Overall, the high prevalence of vitamin D(3) deficiency and the plausible biological mechanisms linking this to CVD risk suggest that the treatment of vitamin D(3) deficiency to prevent CVD is a promising field to explore. Large placebo-controlled randomized clinical trials are urgently needed to determine whether vitamin D supplementation could have any potential benefit in reducing future CVD events and mortality risk.     

Circulating 25-hydroxy-vitamin D and the risk of cardiovascular diseases. Systematic review and meta-analysis of prospective cohort studies

AimsCirculating vitamin D is linked with the risk of cardiovascular disease (CVD). A meta-analysis has yet to explicitly explore correlation between vitamin D and the risk of CVD incidence and recurrent CVD. This meta-analysis examines the association between 25-hydroxy-vitamin D (25(OH)D) and the risk of CVD incidence (fatal, non-fatal, fatal and non-fatal combined events) and the risk of recurrent CVD (fatal, recurrent, and fatal and recurrent combined events). PROSPERO registration-CRD42021251483.Data synthesisA total of 79 studies (46 713 CVD cases in 1 397 831 participants) were included in the meta-analysis, of which 61 studies examined the risk of CVD incidence events, and 18 studies examined risk of recurrent CVD events. The risk of CVD incidence events (RR = 1.34, 95% CI: 1.26–1.43, p < 0.001) and recurrent CVD events (RR = 1.86, 95% CI: 1.46–2.36, p < 0.001) was higher in the lowest than the highest category of circulating 25(OH)D. Dose–response analysis reported a linear association for every 10 ng/ml increment of 25(OH)D and non-fatal CVD incidence events (RR = 0.94; 95% CI = 0.89–0.98, p = 0.005), lower fatal recurrent CVD events (RR = 0.45; 95% CI = 0.32–0.62, p < 0.001) and lower combined recurrent CVD events (RR = 0.80; 95% CI = 0.65–0.97, p = 0.023). A non-linear association was observed between higher 25(OH)D and lower fatal CVD incidence events (P-nonlinear<0.001), lower combined CVD incidence events (P-nonlinear = 0.001), and lower non-fatal recurrent CVD events (P-nonlinear = 0.044).ConclusionsThe lowest category of circulating 25(OH)D was associated with a higher risk of CVD incidence events and recurrent CVD events.     

Hypovitaminosis D and peripheral arterial disease: Emerging link beyond cardiovascular risk factors

Vitamin D has received increasing interest for its beneficial effect on health. Beyond its conventional role in bone metabolism, emerging evidence suggests a possible link between low vitamin D levels and cardiovascular disease (CVD), including peripheral arterial disease (PAD), and cardiovascular risk factors. Vitamin D interacts either directly with the vascular tree or indirectly through its association with cardiovascular risk factors, but the exact mechanism remains controversial. This review outlines the association between hypovitaminosis D and PAD. Both entities are quite prevalent in the general population and, therefore, their potential association might have important clinical implications. Whether vitamin D deficiency represents a novel risk factor for PAD/CVD, and whether vitamin D supplementation would reduce the burden of CVD still remains to be answered. Until then, vitamin D intake is not recommended for PAD/CVD prevention. Outdoor physical activity, coupled with adequate but safe sun exposure, is a healthy lifestyle practice suggested for the prevention of both PAD and hypovitaminosis D.     

Study of IL-6 and vitamin D3 in patients of pulmonary tuberculosis

BackgroundMycobacterium tuberculosis can grow in hostile intracellular environment of macrophages by actively evading macrophage-associated antibacterial activities. The stress response factor contributes this process by releasing inflammatory cytokine Interleukin 6 (IL-6). IL-6 screening of patients with TB may be useful to monitor the progress of infection and to infer the risk of progression to active disease. Vitamin D has a critical role in the innate immune system, in the circulating metabolite and supports induction of pleiotropic antimicrobial responses, through the production of antimicrobial peptides, particularly cathelicidin and its active metabolite. 1,25-dihydoxyvitamin D, has long been known to enhance immune response to mycobacteria. In this study, we have studied the role of IL-6 and Vitamin D3 in M. tuberculosis.Materials and methodsThree groups involved in this study are Control, Category I (newly diagnosed TB) and MDR TB patients. The serum levels of IL-6 and vitamin D3 were measured using chemiluminescence and fully-automated enzyme-linked immunosorbent assay respectively.ResultsThe serum levels of IL-6 were significantly increased, whereas vitamin D3 decreased in TB multidrug-resistant group of patients compared to the newly diagnosed TB patients.ConclusionIL-6 appears to be the major cytokine elaborated by mycobacteria infection as well as play a role in the clinical manifestations and pathological events and hence may function as a potent biomarker of tuberculosis. Since, Vitamin D increases activity of cell-mediated immunity; it can be used as a supplementation during tuberculosis therapy.     

The efficacy of vitamin B12 supplementation for treating vitamin B12 deficiency and peripheral neuropathy in metformin-treated type 2 diabetes mellitus patients: A systematic review

Background and aimsMetformin-treated type 2 diabetes mellitus (T2DM) patients are at higher risk of vitamin B₁₂ deficiency and more severe neuropathy symptoms. There is still no guideline suggesting vitamin B₁₂ supplementation for this population. This study aimed to analyze the efficacy of vitamin B₁₂ supplementation in this population.MethodStudies reporting the efficacy of vitamin B₁₂ supplementation in metformin-treated T2DM patients were systematically searched in PubMed, Cochrane, EBSCOHost, and Scopus following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Additional relevant studies were searched manually through citations. Study quality and risk of bias were assessed using suitable tools.ResultsSeven clinical trials with a total of 506 participants were included. Using the Cochrane's Risk of Bias 2 tools for clinical trials, 4 studies were assessed to have high risk of bias and 3 studies had low risk of bias. There were 5 studies that measured changes in serum vitamin B₁₂ level, all of which reported a statistically significant increase after supplementation. Significant reductions in homocysteine after supplementation were found in 2 studies. Its effect on neuropathy symptoms was still unclear, with 2 studies reporting a significant improvement and 1 study reporting no significant effect.ConclusionsThe results of this systematic review support the implementation of vitamin B₁₂ supplementation for metformin-treated T2DM to prevent or treat vitamin B₁₂ deficiency and neuropathy. More high-quality clinical studies are required to generate quantitative analysis and to encourage supplementation in available guidelines.     

The effects of vitamin D3 supplementation on some metabolic and inflammatory markers in diabetic nephropathy patients with marginal status of vitamin D: A randomized double blind placebo controlled clinical trial

AimsDiabetic nephropathy is known to be an independent risk factor in the progression of renal and cardiovascular disorders. Due to the association between vitamin D deficiency and diabetic nephropathy, vitamin D deficiency in the diabetic nephropathy population, this study conducted to examine the effects of Vitamin D₃ on metabolic and inflammatory parameters in patients with diabetic nephropathy.MethodsThis eight-week, randomized, double-blind, placebo-controlled trial was carried out on 50 diabetic nephropathy patients with marginal status of vitamin D. Participants were randomly assigned to two groups: control and intervention. Participants received a vitamin D3 (50000 IU) supplement weekly on a specific day. Fasting blood samples were collected from all patients at their entry to the study, and eight weeks after intervention.ResultsAnalyses showed significance differences in physical activity between the intervention and placebo groups (P = 0.018). There were no significant differences between the percentage changes of HbA1c, insulin and, inflammatory parameters such as TNF-α and IL-6 (P > 0.05), while the percentage change of FBS was significantly higher in the placebo group compared to the treatment one (P < 0.0001). Lower levels of FBS (P < 0.0001), insulin (P < 0.069), HOMA-IR (P < 0.001), TNF-α (P< 0.002) and IL-6 (P < 0.037) were found after supplementation in treatment group. However, the phosphorous and protein percentage change in urine were lower (P = 0.07) and higher (P = 0.003) between groups.ConclusionsIt was found that vitamin D supplementation can be regarded as an effective way to prevent the progression of diabetic nephropathy by reducing levels of proteinuria, and inflammatory markers such as TNF-α and IL-6.     

The effects of vitamin D supplementation on lipid profiles and oxidative indices among diabetic nephropathy patients with marginal vitamin D status

AimsDiabetic nephropathy is one of the major microvascular complications of type 2 diabetes which insufficient vitamin D might -have a role in it's incidence. This study evaluated the effects of vitamin D supplementation on lipid profiles and oxidative/anti-oxidative indices in marginal vitamin D status patients with diabetic nephropathy.MethodsFor the current paralleled, randomized, double-blinded, placebo-controlled clinical trial, 50 diabetic nephropathy patients with marginal serum vitamin D were selected. Intervention group received 1,25-dihydroxycholecalciferol (50000 IU/week, n = 25), and placebo group (n = 25) received an identical placebo, for 8 weeks. Lipid profiles (LDL, HDL, TG and TC) and oxidative/anti-oxidative markers (TAC, SOD, CAT, GPX and MDA) were measured.ResultsVitamin D supplementation significantly increased vitamin D status in the intervention group, compared to the control group (P = 0.001). The reductions in the serum levels of TG, LDL and TC were significant (P = 0.04, P = 0.006 and P = 0.02, respectively) in the intervention group. The changes in oxidative/anti-oxidative markers and HDL levels were not significant after intervention.ConclusionIn conclusion, vitamin D supplementation for 8 weeks among diabetic nephropathy patients has beneficial effects on serum vitamin D status and dyslipidemia.