antioxidant deficiency contributes to develop and aggravate various chronic diseases , including copd which is sensitive to oxidative stress . supplementation with vitamin c , as an antioxidant , improves antioxidant status in copd.1 several epidemiologic studies2,3 and prospective studies4,5 revealed protective effects of vitamin c intake on copd . vitamin c has symptom - relieving effects on the exacerbation of copd.6 in addition , it improves pulmonary function in copd.7,8 moreover , a recent animal study has revealed that supplementation with vitamin c not only prevents the development of copd but also restores the lung function in copd subjects.9 the korea national health and nutrition examination survey ( knhanes ) is a large - scale survey containing a vast amount of data on demographics , underlying disease , smoking history , lung function , and nutritional status , conducted by the korean centers for disease control and prevention ( kcdc ) . the sample in the present study was selected by a well - designed national program with a complex , multistage probability sample extraction . therefore , the results obtained by this survey using complex analysis can be generalized to the entire korean general population.10,11 thus , knhanes is the best tool for defining and confirming the correlation between vitamin c intake and copd . therefore , in this study , we aimed to confirm the protective effects of vitamin c against copd in the korean general population using knhanes data . this survey used stratification and multiple stages of cluster selection to represent the entire korean general population . we followed guidelines reporting the sample weight and stratification designated by the kcdc ; this information is available at the knhanes website to facilitate obtaining appropriate results , and all the raw data are open to the public ( https://knhanes.cdc.go.kr ) . the institutional review board of gangnam severance hospital approved this study ( approval number : 3 - 2016 - 0195 ) . we included 3,283 subjects aged 40 years or older , who responded to the health interview survey , underwent pulmonary function tests , and responded to questionnaires on smoking history and vitamin c intake from january 2012 to december 2012 . all interview items , including nutritional status , were assessed by questioning the subjects in face - to - face interviews . the resident district was classified as urban ( concordant with dong ) and suburban / rural ( concordant with eup / myun ) . household income was classified into 4 categories ( lowest quartile , q1 ; low - middle quartile , q2 ; high - middle quartile , q3 ; highest quartile , q4 ) . vitamin c intake was also classified into 4 categories ( q1 , < 48.50 mg ; q2 , 48.5084.38 mg ; q3 , 84.38141.63 mg ; q4 , > 141.63 mg ) . the amount smoked ( pack  year ) was calculated based on the duration of smoking history ( year ) , the amount of cigarettes smoked ( pack / day ) , and the frequency of smoking ( day / month ) . smoking history was classified into 4 categories according to the amount smoked ( never smoker , 0 pack - years ; light smoker , 020 pack - years ; medium smoker , 2040 pack - years ; heavy smoker , > 40 pack - years ) . pulmonary function tests , including forced vital capacity ( fvc ) and forced expiratory volume in 1 second ( fev1 ) , were performed using commercially available equipment ( masterlab - ios ; erich jaeger co. , friedburg , germany ) on all the subjects . copd was defined as an fev1/fvc ratio of < 0.7.12 for complex sample survey data analysis , we used the knhanes stratification variables and sampling weight . between the non - copd and copd groups , differences in the mean age and nutritional status were assessed with the independent sample t - test , and differences in the categorized variables were tested using the chi - square test . the prevalence of copd according to smoking history and the amount of vitamin c ingested was compared using the chi - square test . we used spss 18.0 ( spss inc . , chicago , il , usa ) statistical software . this survey used stratification and multiple stages of cluster selection to represent the entire korean general population . we followed guidelines reporting the sample weight and stratification designated by the kcdc ; this information is available at the knhanes website to facilitate obtaining appropriate results , and all the raw data are open to the public ( https://knhanes.cdc.go.kr ) . the institutional review board of gangnam severance hospital approved this study ( approval number : 3 - 2016 - 0195 ) . we included 3,283 subjects aged 40 years or older , who responded to the health interview survey , underwent pulmonary function tests , and responded to questionnaires on smoking history and vitamin c intake from january 2012 to december 2012 . all interview items , including nutritional status , were assessed by questioning the subjects in face - to - face interviews . the resident district was classified as urban ( concordant with dong ) and suburban / rural ( concordant with eup / myun ) . household income was classified into 4 categories ( lowest quartile , q1 ; low - middle quartile , q2 ; high - middle quartile , q3 ; highest quartile , q4 ) . vitamin c intake was also classified into 4 categories ( q1 , < 48.50 mg ; q2 , 48.5084.38 mg ; q3 , 84.38141.63 mg ; q4 , > 141.63 mg ) . the amount smoked ( pack  year ) was calculated based on the duration of smoking history ( year ) , the amount of cigarettes smoked ( pack / day ) , and the frequency of smoking ( day / month ) . smoking history was classified into 4 categories according to the amount smoked ( never smoker , 0 pack - years ; light smoker , 020 pack - years ; medium smoker , 2040 pack - years ; heavy smoker , > 40 pack - years ) . pulmonary function tests , including forced vital capacity ( fvc ) and forced expiratory volume in 1 second ( fev1 ) , were performed using commercially available equipment ( masterlab - ios ; erich jaeger co. , friedburg , germany ) on all the subjects . for complex sample survey data analysis , we used the knhanes stratification variables and sampling weight . between the non - copd and copd groups , differences in the mean age and nutritional status were assessed with the independent sample t - test , and differences in the categorized variables were tested using the chi - square test . the prevalence of copd according to smoking history and the amount of vitamin c ingested was compared using the chi - square test . we used spss 18.0 ( spss inc . , chicago , il , usa ) statistical software . we enrolled 3,283 subjects representing a total of 23,541,704 korean subjects . among all the subjects , we classified all subjects into 2 groups ( non - copd and copd ) , and compared the demographic characteristics between the 2 groups . in males , the prevalence of copd was significantly higher than that in females ( 23.5% vs 6.6% ; p<0.001 ) . the mean age ( standard deviation ) of the copd group ( 64.20.7 ) was significantly older than that in the non - copd group ( 54.50.4 ; p<0.001 ) . the prevalence of copd in subjects who live in suburban / rural areas was significantly higher than that in subjects living in urban areas ( 20.8% vs 12.9% ; p<0.001 ) . in subjects who lived in the general type of house , the prevalence of copd was higher ( 16.6% ) than that in subjects who lived in an apartment ( 9.3% ; p<0.001 ) . the prevalence of copd decreased according to the increase in household income ( p<0.001 ) . subjects who worked in agriculture or fisheries showed a higher prevalence of copd ( 25.0% ) than subjects who had a professional job ( 7.7% ) , or had a service and sales job ( 6.0% ; p<0.001 ) . among never smokers , the prevalence of copd was 7.9% , and the prevalence increased according to the increase in the amount smoked ( 16.7% in light smokers ; 24.2% in medium smokers ; we compared the nutritional status assessed by the self - reported questionnaire between the non - copd and copd group . the amount of food intake ( g ) in the copd group ( 1,320.437.9 ) was significantly less than that in the non - copd group ( 1,462.323.6 ; p=0.001 ) . the amount of potassium ( mg ) ingested in the copd group ( 2,915.485.9 ) was significantly less than that in the non - copd group ( 3,200.058.9 ; p=0.005 ) . the amount of vitamin a and carotene taken by the copd group was also less than that in the non - copd group ( p=0.040 and 0.015 , respectively ) . in the copd group , the retinol intake ( 63.84.9 g ) was significantly less than that in the non - copd group ( 93.46.5 g ; p<0.001 ) . the vitamin c intake ( mg ) was also significantly less than that in the non - copd group ( 93.23.9 vs 122.14.0 ; p<0.001 ; table 2 ) . the prevalence of copd was positively correlated with the amount of smoking , and negatively correlated with the amount of vitamin c ingested . in light smokers , the prevalence of copd in subjects with vitamin c intake in q1 ( 24.7% ) was significantly higher than that in subjects whose vitamin c intake fell in q4 ( 7.0% ; p=0.002 ) . in heavy smokers , the prevalence of copd in subjects with q1 ( 63.0% ) and q2 ( 56.4% ) vitamin c intakes was significantly higher than that in subjects with q3 ( 29.5% ) and q4 ( 32.6% ) vitamin c intakes ( p=0.015 ) . in addition , the prevalence of copd in heavy smokers with vitamin c intake in q3 ( 29.5% ) was lower than that in medium smokers with q1 vitamin c intake ( 36.8% ; figure 1 ) . we selected significant risk factors for copd using univariate analysis with logistic regression of all the variables used in tables 1 and 2 . sex , age , resident district , type of residence , household income , educational level , occupation , smoking history , and amount of retinol intake and vitamin c intake were significant risk factors for copd in the univariate analysis . in the multivariate analysis , sex , age , smoking history , and amount of vitamin c intake were independent risk factors for copd . female gender was a preventative factor ( odds ratio [ or ] , 0.234 ; 95% confidence interval [ ci ] , 0.1440.378 ; p<0.001 ) compared to male gender . aging was a significant risk factor ( or , 1.089 ; 95% ci , 1.0681.110 ; p<0.001 ) . compared to never smokers , medium smokers ( or , 2.192 ; 95% ci , 1.3053.680 ) and heavy smokers ( or , 2.894 ; 95% ci , 1.6415.102 ) were at high risk for copd ( p<0.001 ) . the amount of vitamin c intake was a preventative factor for copd independent of sex , age , and even smoking history ( or , 0.998 ; 95% ci , 0.9960.999 ; p=0.001 ) . a 1-mg increase of vitamin c intake reduced the risk of copd by 0.2% ( table 3 ) . we classified the subjects according to smoking history , and subclassified them according to the amount of vitamin c ingested , and confirmed that the amount of vitamin c is an independent preventative factor for copd when adjusted for age and sex . in light smokers , vitamin c intake in q4 was protective against copd , compared to vitamin c intake in q2 . in particular , in heavy smokers , the risk reduction rate in individuals with vitamin c intake falling in q3 was 76.7% , compared to those with vitamin c intake in q1 ( or , 0.233 ; 95% ci , 0.0940.576 ; table 4 ) . we enrolled 3,283 subjects representing a total of 23,541,704 korean subjects . among all the subjects , we classified all subjects into 2 groups ( non - copd and copd ) , and compared the demographic characteristics between the 2 groups . in males , the prevalence of copd was significantly higher than that in females ( 23.5% vs 6.6% ; p<0.001 ) . the mean age ( standard deviation ) of the copd group ( 64.20.7 ) was significantly older than that in the non - copd group ( 54.50.4 ; p<0.001 ) . the prevalence of copd in subjects who live in suburban / rural areas was significantly higher than that in subjects living in urban areas ( 20.8% vs 12.9% ; p<0.001 ) . in subjects who lived in the general type of house , the prevalence of copd was higher ( 16.6% ) than that in subjects who lived in an apartment ( 9.3% ; p<0.001 ) . the prevalence of copd decreased according to the increase in household income ( p<0.001 ) . subjects who worked in agriculture or fisheries showed a higher prevalence of copd ( 25.0% ) than subjects who had a professional job ( 7.7% ) , or had a service and sales job ( 6.0% ; p<0.001 ) . among never smokers , the prevalence of copd was 7.9% , and the prevalence increased according to the increase in the amount smoked ( 16.7% in light smokers ; 24.2% in medium smokers ; we compared the nutritional status assessed by the self - reported questionnaire between the non - copd and copd group . the amount of food intake ( g ) in the copd group ( 1,320.437.9 ) was significantly less than that in the non - copd group ( 1,462.323.6 ; p=0.001 ) . the amount of potassium ( mg ) ingested in the copd group ( 2,915.485.9 ) was significantly less than that in the non - copd group ( 3,200.058.9 ; p=0.005 ) . the amount of vitamin a and carotene taken by the copd group was also less than that in the non - copd group ( p=0.040 and 0.015 , respectively ) . in the copd group , the retinol intake ( 63.84.9 g ) was significantly less than that in the non - copd group ( 93.46.5 g ; p<0.001 ) . the vitamin c intake ( mg ) was also significantly less than that in the non - copd group ( 93.23.9 vs 122.14.0 ; p<0.001 ; table 2 ) . the prevalence of copd was positively correlated with the amount of smoking , and negatively correlated with the amount of vitamin c ingested . in light smokers , the prevalence of copd in subjects with vitamin c intake in q1 ( 24.7% ) was significantly higher than that in subjects whose vitamin c intake fell in q4 ( 7.0% ; p=0.002 ) . in heavy smokers , the prevalence of copd in subjects with q1 ( 63.0% ) and q2 ( 56.4% ) vitamin c intakes was significantly higher than that in subjects with q3 ( 29.5% ) and q4 ( 32.6% ) vitamin c intakes ( p=0.015 ) . in addition , the prevalence of copd in heavy smokers with vitamin c intake in q3 ( 29.5% ) was lower than that in medium smokers with q1 vitamin c intake ( 36.8% ; figure 1 ) . we selected significant risk factors for copd using univariate analysis with logistic regression of all the variables used in tables 1 and 2 . sex , age , resident district , type of residence , household income , educational level , occupation , smoking history , and amount of retinol intake and vitamin c intake were significant risk factors for copd in the univariate analysis . in the multivariate analysis , sex , age , smoking history , and amount of vitamin c intake were independent risk factors for copd . female gender was a preventative factor ( odds ratio [ or ] , 0.234 ; 95% confidence interval [ ci ] , 0.1440.378 ; p<0.001 ) compared to male gender . aging was a significant risk factor ( or , 1.089 ; 95% ci , 1.0681.110 ; p<0.001 ) . compared to never smokers , medium smokers ( or , 2.192 ; 95% ci , 1.3053.680 ) and heavy smokers ( or , 2.894 ; 95% ci , 1.6415.102 ) were at high risk for copd ( p<0.001 ) . the amount of vitamin c intake was a preventative factor for copd independent of sex , age , and even smoking history ( or , 0.998 ; 95% ci , 0.9960.999 ; p=0.001 ) . a 1-mg increase of vitamin c intake reduced the risk of copd by 0.2% ( table 3 ) . we classified the subjects according to smoking history , and subclassified them according to the amount of vitamin c ingested , and confirmed that the amount of vitamin c is an independent preventative factor for copd when adjusted for age and sex . in light smokers , vitamin c intake in q4 was protective against copd , compared to vitamin c intake in q2 . in particular , in heavy smokers , the risk reduction rate in individuals with vitamin c intake falling in q3 was 76.7% , compared to those with vitamin c intake in q1 ( or , 0.233 ; 95% ci , 0.0940.576 ; table 4 ) . various factors , including sex , age , resident district , type of residence , household income , educational level , occupation , and smoking history , affect the prevalence of copd . in addition , we found that subjects living in suburban / rural areas and general residence types , and subjects with a low income , low educational level , and agriculture or fisheries employment had a higher prevalence of copd . however , these factors may be related to male gender , old age , and a heavy smoking history , which are already well - known risk factors for copd . therefore , multivariate analysis should be performed to define if these factors are independent risk factors for copd . marital status was related to smoking history in a previous study,13 whereas the present study showed that marital status was not significantly associated with copd ; this result should be re - judged based on previous studies because the total number of unmarried subjects was small ( n=41 ; representing 419,691 subjects ; 1.3% of the total number of subjects ) in this study . the main contributing factors for the development of copd are genetic background , exposure to oxidizing agents , and reduced antioxidant capacity.14,15 dietary antioxidants are responsible for antioxidant defenses in the lungs.16 various nutrients , including vitamin c , retinol , tocopherol , and carotenoids , have been proven to be helpful in altering clinical outcomes of copd.3,1719 the present study showed a significant shortage of total nutritional , potassium , vitamin a , carotene , retinol , and vitamin c intake in the copd group compared to the non - copd group . however , the difference in nutritional status between the 2 groups may be due to the difference in total nutritional intake . therefore , again , multivariate analysis would be needed to identify independent risk factors . to define the independent risk factors for copd among the mentioned factors we revealed that male gender , old age , heavy smoking history , and vitamin c were independent risk factors for copd , whereas other factors were not independently significant . except for the well - known risk factors , vitamin c was the only independent risk factor . based on the multivariate analysis , as shown in table 3 , 100 mg of vitamin c intake resulted in a risk reduction of 20.0% . in heavy smokers , ~100 mg of vitamin c intake ( mean of 30.1 mg in q1 vs mean of 110.6 mg in q3 ) led to a marked risk reduction ( 76.7% ) for copd . one - and - a - half apples contains ~100 mg of vitamin c. most nutritional vitamin c supplements contain > 1,000 mg . however , abuse of vitamin c supplements may lead  yet rarely  to acute renal failure.20 therefore , one should carefully consider vitamin c supplements . vitamin c ( also known as ascorbate or l - ascorbic acid ) has antioxidant properties , and plays significant roles in the immune system including allergic reaction , maintenance of connective tissue , and even tumor suppression.2123 low levels of vitamin c have been associated with significantly more wheezing , dyspnea , and exacerbation of copd.2426 dietary vitamin c has also been shown to lower oxidative stress , increase collagen synthesis , and restore vascular endothelial growth factor levels and proliferation of alveolar cells in the lungs.9 extensive studies have shown that vitamin c intake provides protection against the development of copd.1,8,27,28 our results corroborate the findings of these studies . the results obtained by this study are extremely significant , as this study represents almost half of the total korean population ( n=23,541,704 ) . joshi et al have previously revealed the effect of dietary antioxidants on copd in korea.29 we strongly support this previous study with a vast amount of data . although many researchers have attempted to use knhanes data , many such studies ignore complex survey design , which leads to biased results , and overstated significance levels.10 however , we followed the guidelines suggested by the institute that conducted this complex survey , and therefore , the results of the positive effects of vitamin c on copd are deemed trustworthy . first , this is a cross - sectional cohort study . it is not possible to ascertain whether a low intake of vitamin c is the cause or the result of copd . however , we can assume that it is a causal factor , based on the many previous prospective studies mentioned in this paper . the nutritional status was also assessed using self - reported questionnaires , with assistance from an interviewer . measurement of vitamin c using blood sampling may be more helpful to confirm the nutritional status . third , we could not ascertain the optimal dose of vitamin c for preventing copd because the optimal dose differed according to the smoking history . for example , the association between q1 and q3 was stronger than that between q1 and q4 . hence , the or did not follow a linear trend . this might be due to the fact that vitamin c intake greater than the optimal level does not have any additional effects . lastly , height , body mass index , dietary fiber , and cured meat intake may be confounding factors in this study . this large - scale national study suggests that dietary vitamin c intake is protective against copd independent of smoking history in the korean general population .