A systematic review protocol examining the effect of vitamin D supplementation on endothelial function Effect of vitamin D supplementation on inflammation: protocol for a systematic review Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol Effect of a single, oral, high-dose vitamin D supplementation on endothelial function in patients with peripheral arterial disease: a randomised controlled pilot study. Effect of short-term vitamin D supplementation on markers of vascular health in South Asian women living in the UK--a randomised controlled trial. Nutritional Intervention as a Preventive Approach for Cognitive-Related Outcomes in Cognitively Healthy Older Adults: A Systematic Review. Effect of long-term nutraceutical and dietary supplement use on cognition in the elderly: a 10-year systematic review of randomised controlled trials. Effect of dietary interventions in mild cognitive impairment: a systematic review. Supplementation with orange and blackcurrant juice, but not vitamin E, improves inflammatory markers in patients with peripheral arterial disease. Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes. Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease Protocol for Project FACT: a randomised controlled trial on the effect of a walking program and vitamin B supplementation on the rate of cognitive decline and psychosocial wellbeing in older adults with mild cognitive impairment [ISRCTN19227688] Effects of omega-3 polyunsaturated fatty acids on plasma indices of thrombogenesis and inflammation in patients post-myocardial infarction. Effect of phylloquinone (vitamin K1) supplementation for 12 months on the indices of vitamin K status and bone health in adult patients with Crohn's disease. Effects of vitamin D supplementation on markers of vascular function after myocardial infarction--a randomised controlled trial. The effect of vitamin D replacement on markers of vascular health in stroke patients - a randomised controlled trial. Effects of sodium and potassium supplementation on endothelial function: a fully controlled dietary intervention study. Physical rehabilitation interventions for adult patients with critical illness across the continuum of recovery: an overview of systematic reviews protocol Effectiveness of trigger point dry needling for multiple body regions: a systematic review Effectiveness of workplace interventions in rehabilitating musculoskeletal disorders and preventing its consequences among workers with physical and sedentary employment: systematic review protocol Effect of vitamin D supplementation on inflammation and nuclear factor kappa-B activity in overweight/obese adults: a randomized placebo-controlled trial Acute and Chronic Effects of Endurance Running on Inflammatory Markers: A Systematic Review
Introduction Vitamin D has potential benefits for extraskeletal health . These could include an anti-inflammatory effect as well as a reduction in endothelial dysfunction . We aim to provide quality evidence for the hypothesis that supplementation with vitamin D will improve endothelial function ( EF ) , possibly through the abrogation of systemic inflammation . Methods and analysis We will conduct a systematic review of all r and omised controlled trials on  vitamin D supplementation and EF lasting 12 weeks or more . The search will cover the period 2000–2015 and include studies that describe direct measures of EF  , markers of endothelial cell ( EC ) activation  and if concurrently reported , indicators of systemic inflammation  . Study selection will follow the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines and study quality will be assessed by the Jadad score in addition to an evaluation of allocation concealment and data analysis . If sufficient data are available , a meta- analysis will be conducted . The effect sizes will be generated using Hedges ’ g score , for both fixed and r and om effect models . I2 statistics and Galbraith plots will be used to assess heterogeneity and identify their potential sources . Potential publication and small sample size bias will be assessed by visual inspections of funnel plots and also Egger 's test . Meta-regression analysis ( if feasible ) will be conducted with restricted maximum likelihood ( REML ) estimation method , controlling for potential confounders ( demographics , study methods , location , etc ) . A backward elimination process will be applied in the regression modelling procedure . Subgroup analysis , conditional on number of studies retrieved and their sample size , will be stratified on participant disease category , total dose administered , degree of 25(OH)D change and type of supplement used . Ethics and dissemination Formal ethical approval is not required as primary data will not be collected . The results will be disseminated through a peer- review ed publication , conference presentation and the popular press . Trial registration number International Prospect i ve Register for Systematic Review s ( PROSPERO ) number CRD42014013523 Introduction The extraskeletal role of vitamin D is being increasingly recognised . This has important clinical implication s , as vitamin D deficiency has reached epidemic proportions worldwide . Vitamin D has proposed anti-inflammatory properties , yet the role of vitamin D supplementation in reducing inflammation remains largely unknown . The purpose of this review is to investigate the impact of vitamin D supplementation on inflammation , and to identify relevant knowledge gaps in the field . Methods and analysis Medline , CINAHL , EMBASE and All EBM will be systematic ally search ed for r and omised controlled trials ( RCTs ) and systematic review s of RCTs , comparing vitamin D supplementation with placebo , usual care or other pharmacological or non-pharmacological interventions . One review er will assess articles for eligibility according to prespecified selection criteria , after which 2 independent review ers will perform data extraction and quality appraisal . Meta-analyses will be conducted where appropriate . Ethics and dissemination Formal ethical approval is not required as no primary data is collected . This systematic review will identify potential clinical implication s of vitamin D deficiency and supplementation , and will be disseminated through a peer- review ed publication and at conference meetings , to inform future research on the efficacy of vitamin D supplementation for inflammation and inflammatory diseases . PROSPERO registration number CRD42016037104 Background The role of vitamin D in management of depression is unclear . Results from observational and emerging r and omized controlled trials ( RCTs ) investigating the efficacy of vitamin D in depression lack consistency - with some suggesting a positive association while others show a negative or inconclusive association . Methods / Design The primary aim of this study is to conduct a systematic review of RCTs to assess the effect of oral vitamin D supplementation versus placebo on depression symptoms measured by scales and the proportion of patients with symptomatic improvement according to the authors ’ original definition . Secondary aims include assessing the change in quality of life , adverse events and treatment discontinuation . We will conduct the systematic review and meta- analysis according to the recommendations of the Cochrane H and book for Systematic Review s of Interventions . We will search the Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE ( 1966 to present ) , EMBASE ( 1980 to present ) , CINAHL ( 1982 to present ) , PsychINFO ( 1967 to present ) and Clinical Trials.gov . Unpublished work will be identified by search ing two major conferences : the International Vitamin Conference , the Anxiety Disorders and Depression Conference , while grey literature will be acquired by contacting authors of included studies . We will use the r and om-effects meta- analysis to synthesize the data by pooling the results of included studies . Discussion The results of this systematic review will be helpful in clarifying the efficacy of vitamin D supplementation and providing evidence to establish guidelines for implementation of vitamin D for depression in general practice and other relevant setting s. Study registration Unique identifier : CRD42013003849 OBJECTIVE Apart from its role in bone metabolism , vitamin D may also influence cardiovascular disease . The objective of this study was : ( 1 ) to determine the effect of a single , oral , high-dose vitamin D supplementation on endothelial function and arterial stiffness in patients with peripheral arterial disease ( PAD ) and ( 2 ) to investigate the impact of this supplementation on coagulation and inflammation parameters . METHODS In this double-blind , placebo-controlled , interventional pilot study , we screened 76 Caucasian patients with PAD for vitamin D deficiency . Sixty-two were r and omised to receive a single , oral supplementation of 100,000 IU vitamin D3 or placebo . At baseline and after 1 month , we measured serum vitamin D and parathormone levels , and surrogate parameters for cardiovascular disease . RESULTS Sixty-five of 76 patients ( 86 % ) had low 25-hydroxyvitamin D levels ( < 30 ng ml(-1 ) ) ; of those , 62 agreed to participate in the study . At baseline , only parathormone was related to vitamin D. In supplemented patients , vitamin D levels increased from 16.3 ± 6.7 to 24.3 ± 6.2 ng ml(-1 ) ( P < 0.001 ) , with wide variations between single patients ; in the placebo group vitamin levels did not change . Seasonal factors accounted for a decrease of vitamin D levels by 8 ng ml(-1 ) between summer and winter . After 1 month , none of the measured parameters was influenced by vitamin substitution . CONCLUSION In this pilot study , most patients with PAD were vitamin D deficient . Vitamin D supplementation  increased serum 25-hydroxyvitamin D without influencing endothelial function , arterial stiffness , coagulation and inflammation parameters , although the study was underpowered for definite conclusions OBJECTIVE Low vitamin D levels and risk factors for vascular disease are both common in South Asian women . This trial evaluated whether vitamin D supplementation could improve markers of vascular health in South Asian women with low 25-hydroxyvitamin D levels . METHODS Parallel-group , double-blind , r and omised placebo-controlled trial . Healthy South Asian women with baseline serum 25-hydroxyvitamin D levels of < 75 nmol/L were r and omised to receive a single dose of 100,000 units oral vitamin D3 or matching placebo . Outcomes were measured at baseline , 4 and 8 weeks . The primary outcome was change in endothelial function measured using brachial artery flow-mediated dilatation . Secondary outcomes included blood pressure , arterial stiffness , microvascular function measured using laser Doppler iontophoresis , insulin resistance , serum lipids , circulating markers of inflammation , thrombosis and adipokines . RESULTS 50 women were r and omised , 25 to each group . Mean age was 41 years ; mean baseline 25-hydroxyvitamin D level was 27 nmol/L.  25-Hydroxyvitamin D levels rose in the vitamin D group relative to the placebo group by 4 weeks ( 16 nmol/L , 95 % CI 11 to 21 , p < 0.001 ) . There was no improvement in flow-mediated dilatation in the vitamin D group relative to placebo at 4 weeks ( 0.1 % , 95 % CI -0.9 to 1.1 , p = 0.84 ) or 8 weeks ( 0.0 % , 95 % CI -1.4 to 1.4 , p = 0.98 ) . There was no improvement in cholesterol , insulin resistance or markers of inflammation . Both platelet activation inhibitor-1 and tissue plasminogen activator levels fell significantly in the vitamin D group relative to placebo at 8 weeks . CONCLUSION A single large dose of vitamin D3 did not improve blood pressure or endothelial function in South Asian women with low baseline 25-hydroxyvitamin D levels . TRIAL REGISTRATION IS RCT N75081811 The link diet-cognitive function/dementia has been largely investigated in observational studies ; however , there was a lack of evidence from r and omized clinical trials ( RCTs ) on the prevention of late-life cognitive disorders though dietary intervention in cognitively healthy older adults . In the present article , we systematic ally review ed RCTs published in the last four years ( 2014 - 2017 ) exploring nutritional intervention efficacy in preventing the onset of late-life cognitive disorders and dementia in cognitively healthy subjects aged 60 years and older using different levels of investigation ( i.e. , dietary pattern changes/medical food/nutraceutical supplementation/multidomain approach and dietary macro- and micronutrient approaches ) as well as possible underlying mechanisms of nutritional prevention . From the 35 included RCTs , there was moderate evidence that intervention through dietary pattern changes , medical food/nutraceutical supplementation , and multidomain approach improved specific cognitive domains or cognitive-related blood biomarkers . There was high evidence that protein supplementation improved specific cognitive domains or functional status in prefrail older adults without effect on cognitive function . For fatty acid supplementation , mainly long-chain polyunsaturated fatty acids , there was emerging evidence suggesting an impact of this approach in improving specific cognitive domains , magnetic resonance imaging ( MRI ) findings , and /or cognitive-related biomarkers also in selected subgroups of older subjects , although some results were conflicting . There was convincing evidence of an impact of non-flavonoid polyphenol and flavonoid supplementations in improving specific cognitive domains and /or MRI findings . Finally , there was only low evidence suggesting efficacy of intervention with homocysteine-related and antioxidant vitamins in improving cognitive functions , dementia incidence , or cognitive-related biomarkers in cognitively healthy older subjects Nutraceuticals have generated interest as a way to mitigate the cognitive decline in older adults . The aim of this systematic review was to determine the evidence for these cl aims from the scientific literature in r and omised , double-blinded , controlled trials ( duration : ≥1 year ; participants : n≥100 ; age(mean ) : ≥65 years ) . Following Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines , we search ed four electronic data bases ( PubMed , Scopus , CINAHL and Web of Science ) and identified twenty-five studies published between the 15·June·2006 and 14·June·2016 . Interventions included B-vitamins , n-3 fatty acids , antioxidant vitamins and herbs . Of the B-vitamin studies , four found benefits to cognition with supplementation . The first of these B-vitamin studies , in individuals with mild cognitive impairment ( n 266 ; duration = 2 years ) , included benefit to executive function ( P=0·015 ) and improvements in the Mini-Mental State Examination ( MMSE ) among participants with baseline homocysteine above 11·3 µmol/l ( P<0·001 ) . In the same sample , the second study found cognitive benefits  of B-vitamins dependent on the higher baseline plasma n-3 fatty acid status . The third B-vitamin study ( n 900 ; duration = 2 years ) reported improved performance in immediate ( P=0·046 ) and delayed recall ( P=0·013 ) , whereas the fourth study ( n 856 ; duration = 2 years ) reported slower rate of cognitive decline in the MMSE ( P=0·05 ) . One study investigating DHA treatment ( n 402 ; duration = 1·5 years ) revealed the slower rate of cognitive change in apoE e4 non-carriers ( P=0·03 ) . As only five included studies revealed notable benefits , presently based on the specific compounds explored here , there is not compelling evidence to support the use nutraceuticals to improve cognition in the elderly . Future long-term trials of nutraceuticals should investigate interactions with lifestyle , blood biomarkers and genetic risk factors Diet has been investigated in relation to its ability to promote cognitive function . However , evidence is currently limited and has rarely been systematic ally review ed , particularly in a mild cognitive impairment ( MCI ) population . This review examined the effect of diet on cognitive outcomes in MCI patients . A total of five data bases were search ed to find r and omised controlled trial ( RCT ) studies , with diet as the main focus , in MCI participants . The primary outcome was incident dementia and /or Alzheimer 's disease ( AD ) and secondary outcomes included cognitive function across different domains using vali date d neuropsychological tests .  Sixteen studies met the inclusion criteria . There was a high degree of heterogeneity relating to the nature of the dietary intervention and cognitive outcomes measured , thus making study comparisons difficult . Supplementation with vitamin E ( one study , n 516 ) , ginkgo biloba ( one study , n 482 ) or Fortasyn Connect ( one study , n 311 ) had no significant effect on progression from MCI to dementia and /or AD . For cognitive function , the findings showed some improvements in performance , particularly in memory , with the most consistent results shown by B vitamins , including  folic acid  ( one study , n 266 ) ,  folic acid alone  ( one study , n 180 ) ,  DHA and EPA  ( two studies , n 36 and n 86 ) ,  DHA  ( one study , n 240 ) and  flavonol supplementation  ( one study , n 90 ) . The findings indicate that dietary factors may have a potential benefit for cognitive function in MCI patients . Further well- design ed trials are needed , with st and ardised and robust measures of cognition to investigate the influence of diet on cognitive status Inflammation and endothelial activation are associated with an increased risk of CVD and epidemiological evidence suggests an association between levels of markers of inflammation or endothelial activation and the intake of fruit . Also , vitamin E , a fat-soluble antioxidant , has anti-inflammatory properties . We performed a r and omised 2 x 2 factorial , crossover trial to determine the effect of orange and blackcurrant juice ( 500 ml/d ) and vitamin E ( 15 mg RRR-alpha-tocopherol/d ) supplementation on markers of inflammation and endothelial activation in forty-eight patients with peripheral arterial disease . Patients were r and omly allocated to two dietary supplements from the four possible combinations of juice and vitamin E : juice+vitamin E ; juice+placebo ; reference beverage ( sugar drink)+vitamin E ; and reference beverage+placebo . The supplementations were given for 28 d , separated by a 4-week wash-out period . Analysis of main effects showed that juice decreased C-reactive protein ( CRP ) by 11 % and fibrinogen by 3 % while the reference drink increased CRP by 13 % and fibrinogen by 2 % ( P<0.008 and P<0.002 , respectively ) . No significant differences were measured for IL-6 and the endothelial activation markers von Willebr and factor , tissue-plasminogen activator and plasmin activator inhibitor-1 .  Vitamin E supplementation had no significant effects on the various markers . We observed no significant interaction between juice and vitamin E. In this study , orange and blackcurrant juice reduced markers of inflammation , but not markers of endothelial activation , in patients with peripheral arterial disease , relative to sugar drinks BACKGROUND Suboptimal vitamin D status is associated with endothelial dysfunction and an increased risk of cardiovascular diseases but it is unclear whether vitamin D supplementation is beneficial . The aim was to investigate the effect of vitamin D supplementation on endothelial function in patients with type 2 diabetes mellitus ( DM ) . METHODS In a double-blind , placebo-controlled trial , we r and omized 100 type 2 DM patients to vitamin D supplement  ( 5000 IU/day , n = 50 ) or placebo ( controls , n = 50 ) for 12 weeks . Assessment of vascular function with brachial artery flow-mediated dilatation ( FMD ) , circulating levels of endothelial progenitor cells ( EPCs ) and brachial-ankle pulse wave velocity , and metabolic parameter , high-sensitivity C-reactive protein ( hsCRP ) and oxidative stress markers were performed before and after the supplementation . RESULTS After 12 weeks , vitamin D treated patients had significant increases in serum 25-hydroxyvitamin D [ 25(OH)D ] concentration ( treatment effect 34.7 ng/mL , 95 % CI 26.4 - 42.9 , P < 0.001 ) and serum ionized calcium ( treatment effect 0.037 mmol/L , 95 % CI 0.007 - 0.067 , P = 0.018 ) ; decreased serum parathyroid hormone concentration ( treatment effect -0.55 pmol/L , 95 % CI -1.08 to -0.02 , P = 0.042 ) compared to patients who received placebo . Nevertheless , vitamin D supplementation did not improve vascular function as determined by FMD , circulating EPC count or baPWV ( all P > 0.05 ) . Furthermore , hsCRP , oxidative stress markers , low- and high-density lipoprotein and glycated hemoglobin were also similar between two groups ( all P > 0.05 ) . CONCLUSION In patients with type 2 DM , 12 weeks oral supplementation of vitamin D did not significantly affect vascular function or serum biomarkers of inflammation and oxidative stress . CLINICAL TRIAL NUMBER HKCTR-867 , www.hk clinical trials.com We hypothesized that curcumin would improve resistance and conduit artery endothelial function and large elastic artery stiffness in healthy middle-aged and older adults . Thirty-nine healthy men and postmenopausal women ( 45 - 74 yrs ) were r and omized to 12 weeks of curcumin ( 2000 mg/day Longvida ® ; n=20 ) or placebo ( n=19 ) supplementation . Forearm blood flow response to acetylcholine infusions ( FBFACh ; resistance artery endothelial function ) increased 37 % following curcumin supplementation ( 107±13 vs. 84±11 AUC at baseline , P=0.03 ) , but not placebo ( P=0.2 ) . Curcumin treatment augmented the acute reduction in FBFACh induced by the nitric oxide synthase inhibitor NG monomethyl-L-arginine ( L-NMMA ; P=0.03 ) , and reduced the acute increase in FBFACh to the antioxidant vitamin C ( P=0.02 ) , whereas placebo had no effect ( both P>0.6 ) . Similarly , brachial artery flow-mediated dilation ( conduit artery endothelial function ) increased 36 % in the curcumin group ( 5.7±0.4 vs. 4.4±0.4 % at baseline , P=0.001 ) , with no change in placebo ( P=0.1 ) . Neither curcumin nor placebo influenced large elastic artery stiffness ( aortic pulse wave velocity or carotid artery compliance ) or circulating biomarkers of oxidative stress and inflammation ( all P>0.1 ) . In healthy middle-aged and older adults , 12 weeks of curcumin supplementation improves resistance artery endothelial function by increasing vascular nitric oxide bioavailability and reducing oxidative stress , while also improving conduit artery endothelial function Adequate vitamin D levels may promote cardiovascular health by improving endothelial function and down-regulating inflammation . The objective of this pilot trial was to investigate the effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease ( CAD ) . Using a double-blind placebo wait-list control design , 90 subjects with CAD and vitamin D deficiency ( < 20 ng/ml ) were r and omized 1:1 to 50,000 IU of oral ergocalciferol or placebo weekly for 12 weeks . Endothelial function ( reactive hyperemia peripheral arterial tonometry , RH-PAT ) , circulating adhesion molecules , and pro-inflammatory cytokines were measured at baseline and 12 weeks . The median increase in serum 25-vitamin D from baseline was 26 ± 17 ng/ml in the active group and 4 ± 8 ng/ml in the placebo group ( between-group difference = 22 ng/ml , p < 0.001 ) . The median within-subject change in RH-PAT score was 0.13 ± 0.73 with active treatment and −0.04 ± 0.63 with placebo ( between-group difference = 0.17 , p = 0.44 ) . Within-group and between-group differences in intercellular adhesion molecule levels were greater with placebo ( between-group difference = 6 ng/ml , p = 0.048 ) . Vascular cell adhesion molecule levels decreased in both groups by a similar magnitude ( median difference between groups = 8.5 ng/ml , p = 0.79 ) . There was no difference between groups in magnitude of reduction in interleukin (IL)-12 ( −8.6 ng/ml , p = 0.72 ) and interferon-gamma ( 0.52 ng/ml , p = 0.88 ) . No significant differences in blood pressure , e-selectin , high-sensitivity c-reactive protein , IL-6 or the chemokine CXCL-10 were found with treatment . In conclusion , repleting vitamin D levels in subjects with CAD failed to demonstrate any benefits on surrogate markers of cardiovascular health . These results question the role of vitamin D supplementation in modifying cardiovascular disease Background the prevalence of individuals with cognitive decline is increasing since the number of elderly adults is growing considerably . The literature provides promising results on the beneficial effect of exercise and vitamin supplementation on cognitive function both in cognitively healthy as well as in the demented elderly . Methods / Design the design is a two-by-two factorial r and omised controlled trial . The study population consists of independently living elderly , between 70 and 80 years old , with mild cognitive impairment ( MCI ) . In the RCT the effect of two interventions , a walking program and vitamin supplementation , is examined . The walking program ( WP ) is a group-based program aim ed at improving cardiovascular endurance ; frequency two lessons a week ; lesson duration one hour ; program duration one year . Non-walking groups receive a placebo activity program ( PAP ) ( i.e. low intensive non-aerobic group exercises , like stretching ) with the same frequency , lesson and program duration . Vitamin supplementation consists of a single daily vitamin supplement containing 50 mg B6 , 5 mg folic acid and 0,4 mg B12 for one year . Subjects not receiving vitamin supplements are daily taking an identically looking placebo pill , also for a year . Participants are r and omised to four groups 1 ) WP and vitamin supplements ; 2 ) WP and placebo supplements ; 3 ) PAP and vitamin supplements ; 4 ) PAP and placebo supplements . Primary outcome measures are measures of cognitive function . Secondary outcomes include psychosocial wellbeing , physical activity , cardiovascular endurance and blood vitamin levels . Discussion no large intervention study has been conducted yet on the effect of physical activity and vitamin supplementation in a population -based sample of adults with MCI . The objective of the present article is to describe the design of a r and omised controlled trial examining the effect of a walking program and vitamin B supplementation on the rate of cognitive decline in older adults with MCI OBJECTIVE To determine the effects of n-3 PUFAs supplementation on plasma indices of coagulation ( fibrinogen ) , fibrin D-Dimer ( an index of thrombogenesis and fibrin turnover ) , endothelial damage/dysfunction ( von Willebr and factor ( vWf ) ) , platelet activation ( soluble P-selectin ( sP-sel ) ) and inflammation ( interleukin-6 , IL-6 ) in patients following acute myocardial infa rct ion . METHODS Open-labelled r and omised controlled trial . Seventy-seven post-myocardial infa rct ion ( MI ) patients stabilized on st and ard secondary prevention therapy were r and omised either to 3 months ' treatment with Omacor 1 g/day ( n=37 ) or ' usual care ' control ( n=40 ) . Plasma levels of fibrinogen , D-Dimer , vWf , sP-sel , IL-6 and plasma viscosity at baseline and after 3 months were determined . RESULTS At baseline , there were no significant differences between the groups in all research indices , except vWf levels were higher in patients allocated to Omacor supplementation . After 3 months , there were no significant changes in the levels of any research indices in either the Omacor supplemented or the ' usual care ' control patients when compared to baseline . Patients who received Omacor experienced a fall in total cholesterol ( p=0.019 ) , total/HDL-cholesterol ratio ( p=0.009 ) and LDL-cholesterol ( p=0.023 ) . However , the relative changes in plasma lipids and lipoproteins did not differ between the two groups . CONCLUSIONS Three-month supplementation of Omacor at 1 g per day in post-MI patients is not associated with an improvement in the levels of peripheral indices of coagulation potential , endothelial function , platelet reactivity and inflammation Although epidemiological findings support a role for vitamin K status in the improvement of bone indices in adult patients with Crohn 's disease ( CD ) , this needs to be confirmed in double-blind , r and omised controlled trials ( RCT ) with phylloquinone ( vitamin K1 ) . By conducting two RCT , the present study aim ed to first establish whether supplementation with 1000 μg of phylloquinone daily near-maximally suppresses the percentage of undercarboxylated osteocalcin in serum ( % ucOC ; marker of vitamin K status ) in adult patients with CD currently in remission as it does in healthy adults and second determine the effect of supplementation with phylloquinone at this dose for 12 months on the indices of bone turnover and bone mass . The initial dose-ranging RCT was conducted in adult patients with CD ( n 10 per group ) using 0 ( placebo ) , 1000 or 2000 μg of phylloquinone daily for 2 weeks . In the main RCT , the effect of placebo v. 1000 μg vitamin K/d ( both co-administered with Ca ( 500 mg/d ) and vitamin D3 ( 10 μg/d ) ) for 12 months ( n 43 per group ) on the biochemical indices of bone turnover ( determined by enzyme immunoassay ) and bone mass ( determined by dual-energy X-ray absorptiometry ) were investigated . At baseline , the mean % ucOC was 47 % , and this was suppressed upon supplementation with 1000 μg of phylloquinone daily ( - 81 % ; P < 0·01 ) and not suppressed further by 2000 μg of phylloquinone daily . Compared with the placebo , supplementation with 1000 μg of phylloquinone daily for 12 months had no significant effect ( P>0·1 ) on bone turnover markers or on the bone mass of the lumbar spine or femur , but modestly increased ( P < 0·05 ) the bone mass of the total radius . Despite near maximal suppression of serum % ucOC , supplementation with 1000 μg of phylloquinone daily ( with Ca and vitamin D3 ) had no effect on the indices of bone health in adult CD patients with likely vitamin K insufficiency BACKGROUND Low vitamin D levels are common , and are associated with a higher incidence of future vascular events . We tested whether vitamin D supplementation could improve endothelial function and other markers of vascular function in patients with a history of myocardial infa rct ion . METHODS Parallel group , placebo-controlled , double-blind r and omised trial . Patients with a history of myocardial infa rct ion were r and omised to receive 100,000 units of oral vitamin D3 or placebo at baseline , 2 months and 4 months . Outcomes were measured at baseline , 2 and 6 months . Reactive hyperaemia index on fingertip plethysmography was the primary outcome . Secondary outcome measures included blood pressure , cholesterol , C-reactive protein , von Willebr and factor , tumour necrosis factor alpha , E-selectin , B-type natriuretic peptide , thrombomodulin and 25-hydroxyvitamin D levels . RESULTS 75 patients were r and omised , mean age 66 years . 74/75 ( 99 % ) completed 6 month follow-up . 25 hydroxyvitamin D levels increased in the intervention group relative to placebo ( + 13 vs + 1 nmol/L , p=0.04 ) . There was no between-group difference in change in reactive hyperaemia index between baseline and 6 months ( -0.18 vs -0.07 , p=0.40 ) . Of the secondary outcomes , only C-reactive protein showed a significant decline in the intervention arm relative to placebo at 6 months ( -1.3 vs 2.0mg/L , p=0.03 ) . Systolic blood pressure ( + 1.4 vs + 2.3 mmHg , p=0.79 ) , diastolic blood pressure ( + 2.0 vs + 0.8 mmHg , p=0.54 ) and total cholesterol ( + 0.26 vs + 0.24 mmol/L , p=0.88 ) showed no between-group difference at 6 months . CONCLUSIONS Supplementation with vitamin D did not improve markers of vascular function in patients with a history of myocardial infa rct ion BACKGROUND AND AIMS Low vitamin D levels are associated with increased incidence of future cardiovascular events and are common in stroke patients . We tested whether vitamin D supplementation could reduce blood pressure and improve markers of vascular health in patients who had previously suffered a stroke . METHODS AND RESULTS R and omised , placebo-controlled , double-blind trial . Community-dwelling patients with a history of stroke and baseline 25-hydroxyvitamin D levels < 75 nmol/L received 100,000 units of oral vitamin D2 or placebo at baseline . Office and 24 h blood pressure , endothelial function measured by flow-mediated dilatation of the brachial artery , cholesterol , oxidised low density lipoprotein , B-type natriuretic peptide and heart rate turbulence were measured at baseline , 8 weeks and 16 weeks . 58 patients were r and omised . Mean age was 67 years , mean baseline blood pressure 128/72 mmHg , mean baseline 25-hydroxyvitamin D level was 38 nmol/L.  Serum 25-hydroxyvitamin D levels were higher in the intervention group at 8 weeks compared to placebo ( 54 vs 42 nmol/L , P = 0.002 ) and remained higher at 16 weeks . Office systolic and diastolic blood pressure showed no significant change between groups at 8 weeks ( systolic 126.1 vs 131.3 mmHg ; adjusted P = 0.97 ) ; ( diastolic 73.1 vs 74.9 mmHg , adjusted P = 0.15 ) . Flow mediated dilatation was significantly higher in the intervention group at 8 weeks ( 6.9 % vs 3.7 % , adjusted P = 0.007 ) but was not significantly different at 16 weeks . CONCLUSIONS High dose oral vitamin D supplementation did not improve blood pressure but produced short-term improvement in endothelial function in stroke patients with well-controlled baseline blood pressure . CLINICAL TRIALS REGISTRATION IS RCT N28737567 High Na and low K intakes have adverse effects on  blood pressure  , which increases the risk for CVD . The role of endothelial dysfunction and inflammation in this pathophysiological process is not yet clear . In a r and omised placebo-controlled cross-over study in untreated (pre)hypertensives , we examined the effects of Na and K supplementation on endothelial function and inflammation . During the study period , subjects were provided with a diet that contained 2·4 g/d of Na and 2·3 g/d of K for a 10 460 kJ ( 2500 kcal ) intake . After 1-week run-in , subjects received capsules with supplemental Na ( 3·0 g/d ) , supplemental K ( 2·8 g/d ) or placebo , for 4 weeks each , in r and om order . After each intervention , circulating biomarkers of endothelial function and inflammation were measured . Brachial artery flow-mediated dilation ( FMD ) and skin microvascular vasomotion were assessed in sub-groups of twenty-two to twenty-four subjects . Of thirty-seven r and omised subjects , thirty-six completed the study .  Following Na supplementation  , serum endothelin-1 was increased by 0·24 pg/ml ( 95 % CI 0·03 , 0·45 ) , but no change was seen in other endothelial or inflammatory biomarkers . FMD and microvascular vasomotion were unaffected by Na supplementation . K supplementation  reduced IL-8 levels by 0·28 pg/ml ( 95 % CI 0·03 , 0·53 ) , without affecting other circulating biomarkers . FMD was 1·16 % ( 95 % CI 0·37 , 1·96 ) higher after K supplementation than after  placebo . Microvascular vasomotion was unaffected . In conclusion , a 4-week increase in Na intake increased endothelin-1 , but had no effect on other endothelial or inflammatory markers . Increased K intake had a beneficial effect on FMD and possibly IL-8 , without affecting other circulating endothelial or inflammatory biomarkers Background Patients admitted to the intensive care unit with critical illness often experience significant physical impairments , which typically persist for many years following resolution of the original illness . Physical rehabilitation interventions that enhance restoration of physical function have been evaluated across the continuum of recovery following critical illness including within the intensive care unit , following discharge to the ward and beyond hospital discharge . Multiple systematic review s have been published appraising the exp and ing evidence investigating these physical rehabilitation interventions , although there appears to be variability in review methodology and quality . We aim to conduct an overview of existing systematic review s of physical rehabilitation interventions for adult intensive care patients across the continuum of recovery . Methods / design This protocol has been developed according to the Preferred Reporting Items for Systematic Review s and Meta-Analyses Protocol ( PRISMA -P ) guidelines . We will search the Cochrane Systematic Review Data base , Data base of Abstract s of Review s of Effectiveness , Cochrane Central Register of Controlled Trials , MEDLINE , Excerpta Medica Data base and Cumulative Index to Nursing and Allied Health Literature data bases . We will include systematic review s of r and omised controlled trials of adult patients , admitted to the intensive care unit and who have received physical rehabilitation interventions at any time point during their recovery . Data extraction will include systematic review aims and rationale , study types , population s , interventions , comparators , outcomes and quality appraisal method . Primary outcomes of interest will focus on findings reflecting recovery of physical function . Quality of reporting and method ological quality will be appraised using the PRISMA checklist and the Assessment of Multiple Systematic Review s tool . Discussion We anticipate the findings from this novel overview of systematic review s will contribute to the synthesis and interpretation of existing evidence regarding physical rehabilitation interventions and physical recovery in post-critical illness patients across the continuum of recovery . Systematic review registration PROSPERO CRD42015001068 Background : Trigger point dry needling ( TDN ) is commonly used to treat musculoskeletal pain related to myofascial trigger points ( MTrPs ) . To date , no systematic review of high- quality r and omised controlled trials ( RCTs ) investigating TDN to multiple body regions exists . Purpose : The aim of this review is to determine the effectiveness of TDN based on high- quality RCTs for all body regions . Methods : To ensure thorough reporting , Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines were followed as the method ological basis for this systematic review . PubMed , Physiotherapy Evidence Data base ( PEDro ) , Cinahl , Cochrane and reference lists were search ed for the years 2000–2014 and the terms ‘ TDN ’ , ‘ dry needling NOT trigger point ’ , ‘ functional dry needling ’ and ‘ intramuscular manual therapy ’ . Inclusion criteria : RCTs with PEDro scores 6–10 investigating TDN . Exclusion criteria : duplicates , non-human participants , non-English language , exclusive focus on acupuncture or medicinal injections . Three investigators search ed data bases , applied criteria , read and assigned PEDro scores to every RCT . Nineteen studies met the criteria . As compared to either baseline or control groups , significant differences were found for pain ( 14 studies ) , range of motion ( ROM ) ( five studies ) and at least one item on function and quality of life measures ( six studies ) . Limitations : This review was limited by inclusion criteria , timeframe , language and data bases search ed . Conclusion : The majority of high- quality studies included in this review show measured benefit from TDN for MTrPs in multiple body areas , suggesting broad applicability of TDN treatment for multiple muscle groups . Further high- quality research is warranted to st and ardise TDN methods to determine clinical applicability Background Musculoskeletal disorders ( MSDs ) are the leading cause of work disability and sickness absence worldwide . The prevalence of MSDs increases with age , consequently challenging sustainable employability among the growing ageing workforce . Knowledge of feasible and efficient workplace-based interventions to rehabilitate MSD or prevent its consequences is therefore warranted . This systematic review will evaluate the effectiveness of workplace-based interventions on MSDs and its consequences among adult workers with physical and sedentary work tasks , respectively . Methods We will search the following bibliographic data bases : PubMed ( including the data base ‘ MEDLINE ’ ) and Web of Science Core Collection ( including the data bases ‘ Science Citation Index Exp and ed ’ , ‘ Social Sciences Citation Index ’ and ‘ Arts & Humanities Citation Index ’ ) . Manual search es will also be performed . We will include r and omised controlled trials ( RCTs ) and non- RCTs reported in English in which ( 1 ) participants are adult workers with MSD , ( 2 ) interventions are aim ing at rehabilitating pain symptoms of MSD or preventing the consequences of MSD and ( 3 ) interventions are initiated and /or carried out at the workplace . The review will adhere to the ‘ Preferred Reporting Items for Systematic review s and Meta-Analyses ’ ( PRISMA ) guidelines for reporting systematic review s and the Institute for Work and Health ( IWH ) guidelines for workplace-based interventions . For the primary evaluation of the review , the quality assessment and evidence synthesis will conform to the IWH guidelines . Secondary evaluation will include a meta- analysis ( unless the included studies do not allow this due to heterogeneity ) and employ the risk of bias domains recommended by Cochrane along with the Grading of Recommendations , Assessment , Development and Evaluations ( GRADE ) approach on the studies with pain intensity as an outcome . Discussion This systematic review will provide knowledge on effective workplace-based interventions among physical and sedentary workers with MSD . RCTs are considered the most powerful experimental design in clinical trials , but solely including these may be too restrictive to underst and effective workplace-based interventions where r and omised and carefully controlled trials ( RCTs ) are not always possible . In order to maximize practical relevance , the selection process will , therefore , include both RCTs and non- RCTs and the quality assessment and evidence synthesis will conform to IWH guidelines focusing on developing practical guidelines for stakeholders . The result of this work will form the basis for industry-specific evidence -based recommendations on effective workplace-based interventions for rehabilitation of MSDs and its consequences that will later be operationalised into concrete and user-friendly practical tools for workplaces . Systematic review registration International Prospect i ve Register of Systematic Review s ( PROSPERO ) number CRD42018116752 In-vitro studies suggest that vitamin D reduces inflammation by inhibiting nuclear factor kappa-B ( NFκB ) activity . Yet , no trials have examined the effects of vitamin D supplementation on NFκB activity in-vivo in humans . We conducted a double-blind r and omized trial ( RCT ) examining effects of vitamin D supplementation on inflammatory markers and NFκB activity in peripheral blood mononuclear cells ( P BMC s ) . Sixty-five overweight/obese , vitamin D-deficient ( 25-hydroxyvitamin D [ 25(OH)D ] ≤ 50 nmol/L ) adults were r and omized to a single 100,000 IU bolus followed by 4,000 IU daily cholecalciferol or matching placebo for 16 weeks . We measured BMI , % body fat , serum 25(OH)D , high-sensitivity C-reactive protein ( hsCRP ) , tumour necrosis factor ( TNF ) , monocyte chemoattractant protein-1 ( MCP-1 ) , interferon-gamma ( IFN-γ ) , several interleukins , and NFκB activity in P BMC s. Fifty-four participants completed the study . Serum 25(OH)D concentrations  increased with vitamin D supplementation compared to placebo ( p < 0.001 ) . Vitamin D and placebo groups did not differ in any inflammatory markers or NFκB activity ( all p > 0.05 ) . Results remained non-significant after adjustment for age , sex , and % body fat , and after further adjustment for sun exposure , physical activity , and dietary vitamin D intake . Although in-vitro studies report anti-inflammatory effects  of vitamin D , our RCT data show no effect of vitamin D supplementation on inflammatory markers or NFκB activity in-vivo in humans In order to underst and the effect of endurance running on inflammation , it is necessary to quantify the extent to which acute and chronic running affects inflammatory mediators . The aim of this study was to summarize the literature on the effects of endurance running on inflammation mediators . Electronic search es were conducted on PubMED and Science Direct with no limits of date and language of publication . R and omized controlled trials ( RCTs ) and non-r and omized controlled trials ( N RCTs ) investigating the acute and chronic effects of running on inflammation markers in runners were review ed by two research ers for eligibility . The modified Downs and Black checklist for the assesssments of the method ological quality of studies was subsequently used . Fifty-one studies were finally included . There were no studies with elite athletes . Only two studies were chronic interventions . Results revealed that acute and chronic endurance running may affect anti- and pro-inflammatory markers but method ological differences between studies do not allow comparisons or generalization of the results . The information provided in this systematic review would help practitioners for better design ing further studies while providing reference values for a better underst and ing of inflammatory responses after different running events . Further longitudinal studies are needed to identify the influence of training load parameters on inflammatory markers in runners of different levels and training background
Evidence from the studies included in this systematic review did not demonstrate that vitamin D supplementation in adults , results in an improvement in circulating inflammatory and endothelial function biomarkers/parameters .
This systematic review does not therefore support the use of vitamin D supplementation as a therapeutic or preventative measure for CVD in this respect
This systematic review aims to evaluate r and omised controlled trials ( RCTs ) investigating the effect of vitamin D supplementation on  endothelial function and inflammation in adults .