***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background —Carotenoids are hypothesized to explain some of the protective effects of fruit and vegetable intake on risk of cardiovascular disease . The present study assessed the protective effects of the oxygenated carotenoid lutein against early atherosclerosis . Methods and Results —Epidemiology : Progression of intima-media thickness ( IMT ) of the common carotid arteries over 18 months was determined ultrasonographically and was related to plasma lutein among a r and omly sample d cohort of utility employees age 40 to 60 years ( n=480 ) . Coculture : The impact of lutein on monocyte response to artery wall cell modification of LDL was assessed in vitro by quantification of monocyte migration in a coculture model of human intima . Mouse models : The impact of lutein supplementation on atherosclerotic lesion formation was assessed in vivo by assigning apoE-null mice to chow or chow plus lutein ( 0.2 % by weight ) and LDL receptor-null mice to Western diet or Western diet plus lutein .  IMT progression declined with increasing quintile of plasma lutein ( P for trend=0.007 , age-adjusted;P = 0.0007 , multivariate ) . Covariate-adjusted IMT progression ( mean±SEM ) was 0.021±0.005 mm in the lowest quintile of plasma lutein , whereas progression was blocked in the highest quintile ( 0.004±0.005 mm;P = 0.01 ) . In the coculture , pretreatment of cells with lutein inhibited LDL-induced migration in a dose-dependent manner ( P < 0.05 ) . Finally , in the mouse models , lutein supplementation reduced lesion size 44 % in apoE-null mice ( P = 0.009 ) and 43 % in LDL receptor-null mice ( P = 0.02 ) . Conclusions —These epidemiological , in vitro , and mouse model findings support the hypothesis that increased dietary intake of lutein is protective against the development of early atherosclerosis BACKGROUND AND AIMS Cardiovascular diseases are the major cause of mortality among diabetic patients . The concentration of malondialdehyde ( MDA ) and homocysteine is believed to play a role in cardiovascular diseases . Omega-3 fatty acid supplementation could be effective in some diabetes complications and in the control of the glycemic index . However , it may increase lipid peroxidation . The objective of this study was to determine the effect of omega-3 fatty acids on the concentration of homocysteine and MDA in diabetic patients . METHODS AND RESULTS A r and omized double-blind , placebo-controlled clinical trial was conducted on 81 patients with type 2 diabetes . The patients were r and omly assigned to either the treatment or control groups . Each subject received three capsules of omega-3 fatty acids or a placebo every day for a period of 2months . The two groups were similar in terms of body mass index and food intake . At the beginning of the study and after 2months of supplementation their levels of HbA(1)c , homocysteine , MDA , C-reactive protein ( CRP ) , total cholesterol , LDL-cholesterol and fasting blood sugar ( FBS ) were determined . Due to omega-3 fatty acid supplementation , homocysteine was changed significantly in both treatment and control groups up to -3.10mumol/L and 0.10mumol/L respectively , and HbA(1)c decreased by 0.75 % in the treatment group and increased by 0.26 % in the control group . However , the changes in fasting blood sugar ( FBS ) , malondialdehyde ( MDA ) , C-reactive protein ( CRP ) , total cholesterol and LDL-cholesterol levels were not significant . CONCLUSION The consumption of omega-3 fatty acid supplements ( 3g/day ) for 2months decreases the levels of homocysteine in diabetic patients with no change in FBS , MDA and CRP levels Background —Some epidemiological studies have shown that increased iron stores are associated with increased cardiovascular events . Redox-active iron may contribute to lipid peroxidation , endothelial cell activation , and generation of reactive oxygen species ( especially hydroxyl radical , via Fenton chemistry ) . Increased oxidative stress is associated with impaired action of endothelium-derived nitric oxide in patients with atherosclerosis . Methods and Results —To test the hypothesis that reducing vascular iron stores would reverse endothelial dysfunction , we examined the effects of the iron chelator deferoxamine ( 500 mg intra-arterially over 1 hour ) on vasomotor function in forearm resistance vessels of patients with coronary artery disease by venous occlusion plethysmography . Patients with coronary artery disease had impaired endothelium-dependent vasodilation in response to methacholine compared with healthy control subjects ( P < 0.001 ) . Deferoxamine infusion decreased serum iron levels ( P < 0.001 ) . Deferoxamine improved the blood flow response to methacholine in patients with coronary artery disease ( P < 0.01 by 2-way repeated- measures ANOVA ) but had no effect on the response to sodium nitroprusside . In normal volunteers , deferoxamine had no effect on the response to methacholine . The nitric oxide synthase inhibitor NG-monomethyl-l-arginine abolished augmentation of the methacholine response associated with deferoxamine . The hydroxyl radical scavenger mannitol had no effect on the methacholine response . Conclusions —Deferoxamine improved nitric oxide – mediated , endothelium-dependent vasodilation in patients with coronary artery disease . These results suggest that iron availability contributes to impaired nitric oxide action in atherosclerosis BACKGROUND Oxidative stress and inflammation are crucial in atherogenesis . alpha-Tocopherol is both an antioxidant and an antiinflammatory agent . OBJECTIVE We evaluated the effect of RRR-alpha-tocopherol supplementation on carotid atherosclerosis in patients with stable coronary artery disease ( CAD ) on drug therapy . DESIGN R and omized , controlled , double-blind trial compared RRR-alpha-tocopherol ( 1200 IU/d for 2 y ) with placebo in 90 patients with CAD .  Intimal medial thickness ( IMT ) of both carotid arteries was measured by high-resolution B-mode ultrasonography at 0 , 1 , 1.5 , and 2 y. At 6-mo intervals , plasma alpha-tocopherol concentrations , C-reactive protein ( CRP ) , LDL oxidation , monocyte function ( superoxide anion release , cytokine release , and adhesion to endothelium ) , and urinary F(2)-isoprostanes were measured . RESULTS alpha-Tocopherol concentrations were significantly higher in the alpha-tocopherol group but not in the placebo group . High-sensitivity CRP concentrations were significantly lowered with alpha-tocopherol supplementation than with placebo ( 32 % ; P < 0.001 ) . alpha-Tocopherol supplementation significantly reduced urinary F(2)-isoprostanes ( P < 0.001 ) and monocyte superoxide anion and tumor necrosis factor release compared with baseline and placebo ( P < 0.001 ) . No significant difference was observed in the mean change in total carotid IMT in the placebo and alpha-tocopherol groups . In addition , no significant difference in cardiovascular events was observed ( P = 0.21 ) . CONCLUSIONS High-dose RRR-alpha-tocopherol supplementation in patients with CAD was safe and significantly reduced plasma biomarkers of oxidative stress and inflammation but had no significant effect on carotid IMT during 2 INTRODUCTION Observational studies have suggested a causal relationship between hyperhomocysteinemia and cardiovascular complications such as stroke and ischemic heart disease . The Homocysteine Lowering Trialists ' Collaboration has shown that daily administration of folic acid can significantly decrease homocysteine levels up to 25 % . Aim of this study was to investigate the effect of daily supplementation of folic acid ( 5 mg ) on IMT after 18 months of treatment in patients with at least one cardiovascular risk factor . METHODS We enrolled 103 patients with at least one cardiovascular risk factor who were r and omized to receive either a daily dose of 5 mg folic acid ( group I , n=53 ) or placebo ( group II , n=50 ) for 18 months . RESULTS After 18 months of folic acid supplementation , homocysteine levels were significantly reduced in the active treatment group compared to a non-significant increase in the placebo group . Folic acid levels were markedly increased in the former group and non-significantly reduced in the latter . Significant regression of carotid IMT was observed ( 0.961+/-0.092 to 0.933+/-0.077 mm , p<0.001 ) compared to significant IMT progression in the placebo group ( 0.964+/-0.099 to 0.984+/-0.094 mm ) . CONCLUSION Folic acid supplementation results in significant IMT reduction after 18 months in patients with at least one cardiovascular risk OBJECTIVE Hyperhomocysteinemia is an independent risk factor for atherosclerotic vascular disease in chronic hemodialysis patients . This stratified r and omized controlled trial was design ed to measure the effect of high dose oral vitamin B6 , vitamin B12 , and folic acid on homocysteine levels , and to evaluate the effect on atherosclerosis as measured by Intima-Media Thickness ( IMT ) of carotid arteries . MATERIAL AND METHOD Fifty-four chronic hemodialysis patients with hyperhomocysteinemia were r and omized to receive oral 15 mg folic acid , 50 mg vitamin B6 , and 1 mg vitamin B12 daily ( treatment group ) or oral 5 mg folic acid alone ( control group ) for 6 months . Homocysteine level and IMT were measured in both groups . RESULTS At 6 months , homocysteine levels in the treatment group were significantly reduced from 27.94 + /- 8.54 to 22.71 + /- 3.68 mmol/l ( p = 0.009 ) and were not significantly increased from 26.81 + /- 7.10 to 30.82 + /- 8.76 mmol/l in control group ( p = 0.08 ) . Mean difference between both groups was statistically significant ( p = 0.002 ) . There was no significant difference of IMT of carotid arteries , however , a tendency that the treatment group would have less thickness was observed ( 0.69 + /- 0.29 mm and 0.62 + /- 0.16 mm , p = 0.99 ) . CONCLUSION Treatment of hyperhomocysteinemia in chronic hemodialysis patients with daily oral 15 mg folic acid , 50 mg vitamin B6 , and 1 mg vitamin B12 for 6 months decreases homocysteine levels and tends to reduce IMT of carotid arteries . A long term study for the prevention of atherosclerosis is warranted Abstract —Although a number of epidemiological studies have evaluated the association between & bgr;-carotene and the risk of cardiovascular diseases , there has been little research on the role of lycopene , an acyclic form of & bgr;-carotene , with regard to the risk of cardiovascular disease . We investigated the relationship between plasma concentrations of  lycopene  and intima-media thickness of the common carotid artery wall ( CCA-IMT ) in 520 middle-aged men and women ( aged 45 to 69 years ) in eastern Finl and . They were examined from 1994 to 1995 at the baseline of the Antioxidant Supplementation in Atherosclerosis Prevention ( ASAP ) study , a r and omized trial concerning the effect of vitamin E and C supplementation on atherosclerotic progression . The subjects were classified into 2 categories according to the median concentration of plasma lycopene ( 0.12 & mgr;mol/L in men and 0.15 & mgr;mol/L in women ) . Mean CCA-IMT of the right and left common carotid arteries was 1.18 mm in men and 0.95 mm in women with plasma lycopene levels lower than the median and 0.97 mm in men ( P < 0.001 for difference ) and 0.89 mm in women ( P = 0.027 for difference ) with higher levels of plasma lycopene . In ANCOVA adjusting for cardiovascular risk factors and intake of nutrients , in men , low levels of plasma lycopene were associated with a 17.8 % increment in CCA-IMT ( P = 0.003 for difference ) . In women , the difference did not remain significant after the adjustments . We conclude that low plasma lycopene concentrations are associated with early atherosclerosis , manifested as increased CCA-IMT , in middle-aged men living in eastern Finl and Background —Activation of the renin-angiotensin-aldosterone system 
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RESULTS Although not all studies found consistent results , the weight of the evidence suggests that high intakes and /or circulatory levels of magnesium , as well as vitamin D and the vitamin B group , may be associated with lower carotid IMT or reduced progression of carotid IMT .
The majority of studies did not find any significant association between vitamin E and C and carotid IMT .
Less evidence was available for associations of retinol , zinc , and iron with carotid IMT .
CONCLUSIONS In general , the current evidence concerning micronutrient intake and carotid IMT is largely inconclusive .
Pragmatic clinical trials are required to determine whether dietary or supplemental intake of specific micronutrients alters carotid IMT , which is a surrogate measure of cardiovascular risk