epidemiological studies show that diets high in fruits and vegetables are associated with lower risk of cardiovascular disease , stroke , and cancer , and with increased longevity ( keli et al 1996 ; joshipura et al 1999 ; voko et al 2003 ; fung et al 2004 ) . whether these protective effects are directly attributable to vitamins c or e or other food constituents is not known . cerebral ischemia results in vascular ( endothelial ) damage , and tissue injury ( infarction ) . tissue injury in the acute phase generates increase production of oxygen ( o2 ) radical , which in turn triggers necrosis in the acute phase , inflammatory responses in the subacute phase , and apoptosis in the chronic phase . this oxidative stress increases the permeability of the blood - brain barrier leading to edema , and tends to increase lesion volume and neurological impairment in stroke ( leinonen et al 2000 ) . cherubini and colleagues ( 2000 ) , gariballa and colleagues ( 2002 ) , and sanchez - moreno and colleagues ( 2004 ) , in their respective studies have shown that the serum levels of most of the antioxidants ( including vitamin c levels ) are reduced immediately after an acute ischemic stroke compared with controls , presumably as a consequence of increased oxidative stress . inflammatory markers ( c - reactive protein , intercellular adhesion molecule-1 , monocyte chemotactic protein-1 ) are increased simultaneously . intervention studies with vitamin c have shown no change in markers of oxidation or clinical benefit in chronic diseases particularly diabetes mellitus ( padayatty et al 2003 ) . schutte and colleagues ( 2004 ) , studied the markers of vascular function in 31 young healthy male adults , who were administered a daily dosage of 1000 mg vitamin c , 800 mg vitamin e , and 10 mg folate . beneficial decreases in diastolic blood pressure due to increase in arterial compliance after 12 weeks of vitamin supplementation was noted , while no statistically significant changes were observed with other cardiovascular variables such as systolic blood pressure , stroke volume , heart rate , cardiac output , vascular resistance , and arterial compliance . in contrast to the epidemiological data on diet and stroke incidence and severity , and clinical intervention studies in the acute phase , no prior studies have addressed the effectiveness of vitamin c supplementation on functional recovery in patients undergoing rehabilitation after an ischemic stroke . of the stroke patients admitted to our designated acute stroke rehabilitation unit over a 12-month period , 23 recovering ischemic stroke patients on vitamin c were matched to 23 recovering ischemic stroke patients not on vitamin c ( control ) . the inclusion criteria were : first ischemic stroke event , and neuroimaging ( computed tomography and/or magnetic resonance imaging ) showing ischemic lesion corresponding to the clinical signs and symptoms . patients were matched for age ; sex , onset - to - admission , and admission total functional independence measure ( tfim ) , which are factors known to influence functional motor recovery . the physician and the rehabilitation team members prospectively recorded the data in a computerized stroke database . ischemic stroke patients who were undernourished ( defined as significant weight loss , and/or 90% or less ideal body weight for age and sex , and an admission serum albumin < 3.4 gm / dl ) and/or had the presence of pressure sores were administered 1000 mg of vitamin c daily as part of its treatment protocol . our institution s institutional review board approval was not obtained because administration of vitamin c for undernourished patients and/or presence of pressure sore are considered a part of the standard of care at our institution . the primary outcome measures were : change in the tfim score , fim - cognition ( fim - cog ) , and fim - motor sub - scores . the secondary outcome measures were : discharge disposition ( home discharge vs. long - term care facility ) and length of stay ( los ) . the functional independence measure ( fim ) tool was used to measure the degree of disability as well as the progress the patients made through medical rehabilitation programs ( granger 1998 ) . the fim scale is a reliable ( stineman et al 1996 ) and a valid functional independence measure ( stineman and maislin 2000 ) . the fim has become the standard functional assessment measures of self - care and mobility in rehabilitation medicine in the united states . the possible total score ranges from 18 ( maximum level of dependence ) to 126 ( highest level of independence ) . stroke rehabilitation team members who are fim - certified scored the admission and discharge total fim score . continuous and nominal variables between the two groups were analyzed using student s t - test and chi - square analyses . the statistical analysis was carried out by commercial statistical software package stat view ( version 5.0.1 sas institute inc . table 1 presents the demographics of our study sample ( n = 46 ) for the 2 groups based on presence or absence of vitamin c supplementation intake . the mean age ( sd ) of our patients was 76  11 years ( range 4989 years ) . the vitamin c treated ( n = 23 ) versus control ( n = 23 ) group were well matched for : age ( p = 0.84 ) , m / f ratio ( p = 1.0 ) , onset - to - admission ( p = 0.38 ) , prior level of physical independence ( p = 1.0 ) , and admission tfim ( p = 0.99 ) ( table 1 ) . there were 15 patients in the vitamin c group and only 1 patient in the control group ( p = 0.0001 ) who had pressure sores . the changes in tfim ( p = 0.20 ) , fim - cog ( p = 0.41 ) , and fim - motor ( p = 0.21 ) sub - scores were consistently less in the vitamin c treated group compared with the controls but the differences did not reach statistical significance ( table 2 ) . similarly , no significant differences were found between the 2 groups for los ( p = 0.59 ) , and discharge disposition to home / or institution ( p = 0.60 ) . in view of the lack of difference between the primary and secondary outcome measures between the 2 groups , a post - hoc analysis between the two groups for the primary outcome variables in the undernourished ischemic stroke patients ( n = 8) versus their cognate controls ( n = 8) was undertaken . the p value ( 0.07 , but power < 0.8 ) failed to reach pre - set levels for statistical significance ( p < 0.05 ) , but possibly suggested that individual displaying evidence of malnourishment had worse outcomes . of the stroke patients admitted to our designated acute stroke rehabilitation unit over a 12-month period , 23 recovering ischemic stroke patients on vitamin c were matched to 23 recovering ischemic stroke patients not on vitamin c ( control ) . the inclusion criteria were : first ischemic stroke event , and neuroimaging ( computed tomography and/or magnetic resonance imaging ) showing ischemic lesion corresponding to the clinical signs and symptoms . patients were matched for age ; sex , onset - to - admission , and admission total functional independence measure ( tfim ) , which are factors known to influence functional motor recovery . the physician and the rehabilitation team members prospectively recorded the data in a computerized stroke database . ischemic stroke patients who were undernourished ( defined as significant weight loss , and/or 90% or less ideal body weight for age and sex , and an admission serum albumin < 3.4 gm / dl ) and/or had the presence of pressure sores were administered 1000 mg of vitamin c daily as part of its treatment protocol . our institution s institutional review board approval was not obtained because administration of vitamin c for undernourished patients and/or presence of pressure sore are considered a part of the standard of care at our institution . the primary outcome measures were : change in the tfim score , fim - cognition ( fim - cog ) , and fim - motor sub - scores . the secondary outcome measures were : discharge disposition ( home discharge vs. long - term care facility ) and length of stay ( los ) . the functional independence measure ( fim ) tool was used to measure the degree of disability as well as the progress the patients made through medical rehabilitation programs ( granger 1998 ) . the fim scale is a reliable ( stineman et al 1996 ) and a valid functional independence measure ( stineman and maislin 2000 ) . the fim has become the standard functional assessment measures of self - care and mobility in rehabilitation medicine in the united states . a fim item score of seven is categorized as  complete independence  , while a score of one is total assist  . the possible total score ranges from 18 ( maximum level of dependence ) to 126 ( highest level of independence ) . stroke rehabilitation team members who are fim - certified scored the admission and discharge total fim score . continuous and nominal variables between the two groups were analyzed using student s t - test and chi - square analyses . the statistical analysis was carried out by commercial statistical software package stat view ( version 5.0.1 sas institute inc . table 1 presents the demographics of our study sample ( n = 46 ) for the 2 groups based on presence or absence of vitamin c supplementation intake . the mean age ( sd ) of our patients was 76  11 years ( range 4989 years ) . the vitamin c treated ( n = 23 ) versus control ( n = 23 ) group were well matched for : age ( p = 0.84 ) , m / f ratio ( p = 1.0 ) , onset - to - admission ( p = 0.38 ) , prior level of physical independence ( p = 1.0 ) , and admission tfim ( p = 0.99 ) ( table 1 ) . there were 15 patients in the vitamin c group and only 1 patient in the control group ( p = 0.0001 ) who had pressure sores . the changes in tfim ( p = 0.20 ) , fim - cog ( p = 0.41 ) , and fim - motor ( p = 0.21 ) sub - scores were consistently less in the vitamin c treated group compared with the controls but the differences did not reach statistical significance ( table 2 ) . similarly , no significant differences were found between the 2 groups for los ( p = 0.59 ) , and discharge disposition to home / or institution ( p = 0.60 ) . in view of the lack of difference between the primary and secondary outcome measures between the 2 groups , a post - hoc analysis between the two groups for the primary outcome variables in the undernourished ischemic stroke patients ( n = 8) versus their cognate controls ( n = 8) was undertaken . the p value ( 0.07 , but power < 0.8 ) failed to reach pre - set levels for statistical significance ( p < 0.05 ) , but possibly suggested that individual displaying evidence of malnourishment had worse outcomes . in this retrospective , case - study , administration of vitamin c supplementation did not improve functional recovery in ischemic stroke patients . however , ischemic stroke patients who had pressure sores and were assigned to the vitamin c group had a much lesser change in the functional outcome scores compared with those assigned to the control group . we are unable to explain the results of these findings . moreover , the finding of this study is in agreement with the result of other randomized control trials of vitamin c , e , and -carotene supplementations in high - risk patients with occlusive arterial disease or diabetes . in these cases vitamin c supplementation had no effect on the incidence of any type of vascular disease ( fatal and nonfatal myocardial infarction and stroke ) , nor did it produce any significant reductions in the 5-year mortality . this result was found despite significant increases in the plasma concentrations of these vitamins ( hpscg 2002 ) . confounding factors which may have been responsible for this lack of difference between the 2 groups associated with our study include : 1 ) inappropriate timing of the vitamin c administration . most of the oxidative stress damage is said to occur in the initial 2448 hours post - stroke ( keli et al 1996 ) , when one would expect a better response to antioxidants administration . 2 ) inappropriate dosing of vitamin c. it is possible that the dose of vitamin c was not high enough to exert its desired effect ( hathcock et al 2005 ) . 3 ) vitamin c may be a weak antioxidant in vivo , and its antioxidant effect may be more effective when given together with other antioxidant vitamins , as typically occurs in the diet ( willett and stampfer 2001 ) , rather than when taken by itself alone . 4 ) the pro - oxidant effect of vitamin c could be a mitigating factor . in vitro studies have shown that vitamin c has the ability to act as a pro - oxidant by chemically catalyzing hydroxyl - radical formation in the presence of metal , such as iron ( guo et al 2002 ; bailey et al 2006 ) . recent double - blind placebo controlled in vivo study of 22 patients undergoing vascular surgery for elective abdominal aortic aneurysm , and by - pass repair found vitamin c prophylaxis to promote oxidative lipid damage during surgical ischemia - reperfusion ( podmore et al 1998 ) . 5 ) though our groups were ( demographically and entry fim ) case - control , the vitamin c group was predominantly undernourished compared with the nonvitamin c group . this study is limited by three considerations : i ) the retrospective analysis of computerized stroke patient data , which inherently constrains the ability to randomize the patient population ; ii ) the small sample size , which limits the types of conclusions that can be tested statistically , eg , because of the potential for type ii statistical errors , and ; iii ) the subjects though matched for variables known to influence functional outcomes , they could not be matched for nutritional status or for pressure sores without changing the standard of care at our hospital . while this does place some constraints on the potential to draw conclusions from our data , it is possible that the observed trend toward worse outcomes for vitamin c - treated patients might be at least partially independent of the pre - entrance status of these individual . this is consistent with the recently published study showing a detrimental effect of vitamin c in surgical patients noted above ( podmore et al 1998 ) . finally , our data suggest consideration , such as matching for nutritional status should be considered for future prospective , randomized trials . this study suggests that vitamin c supplementation in 1 gm dosage has no impact on motor recovery after ischemic stroke . retrospective subgroup analysis of a small sub - population ( n = 8) suggests a possible negative association between undernourished ischemic stroke patients , vitamin c treatment , or the combination of these factors in a rehabilitation population .
background and purpose : epidemiological studies have associated increased dietary intake of antioxidants ( vitamin c , e , and -carotene ) in preventing and decreasing the extent of ischemic brain injury . 
 the effect of vitamin c supplementation on functional recovery after stroke has not been studied.method:in this retrospective , case - control study of 23 patients with ischemic stroke taking vitamin c were identified and matched for age , sex , onset to admission , and admission total functional independence measure ( tfim ) with 23 patients with ischemic stroke not taking vitamin c supplementation . 
 vitamin c 1000 mg daily was prescribed on admission to our unit mainly to patients who were undernourished ( defined as significant weight loss and/or 90% or less ideal body weight for age and sex ) and those with pressure sores . 
 the outcome measures were : change in the tfim , fim - cognition ( fim - cog ) , and fim - motor sub - scores , discharge disposition , and length of stay ( los).results : the change in tfim ( 20  13 standard deviation [ sd ] vs. 26  6 , p = 0.20 ) , fim - cog ( 3  3 sd vs. 4  5 , p = 0.41 ) , fim - motor ( 15  11 sd vs. 20  13 , p = 0.21 ) sub - scores were less in the vitamin c treated group , but these differences did not reach statistical significance . similarly , no significant differences were found in los ( 21  9 sd vs. 23  9 , p = 0.59 ) , and discharge disposition ( home / institution ) ( 9/10 vs. 13/9 , p = 0.60 ) between the vitamin c and the control groups.conclusion:this study suggests vitamin c supplementation did not enhance functional recovery in undernourished ischemic stroke patients .