The prevalence of metabolic syndrome has increased due to underactivity and overeating. The Korean National Health and Nutrition Examination Survey 2007-2010 reported that the prevalence rates of metabolic syndrome are 31.9% in Korean men and 25.6% in Korean women.¹⁾ Metabolic syndrome is associated with the development of cardiovascular disease, thus, the cardiovascular mortality in metabolic syndrome patients is 2 to 3 times higher than that of the general population.^2,3) Oxidative stress, on the other hand, is an imbalance which occurs in the form of overproduced reactive oxygen or a shortage of antioxidants, and is associated with the development of metabolic syndrome.⁴⁾

Almost all metabolic syndrome patients suffer from abdominal obesity. An excessive accumulation of fat leads to enhanced production of oxidative stress. Increased oxidative stress in abdominal adipocytes may yield various pro-inflammatory adipocytokines and fatty acids.⁵⁾ Thus, oxidative stress exacerbates metabolic syndrome factors such as insulin resistance, hypertriglyceridemia, decrement of high density lipoprotein (HDL) cholesterol, and hypertension.^6-8)

However, there have been domestic studies on the relationship between oxidative stress and metabolic syndrome. Therefore, this study examined the relationship between factors of metabolic syndrome and oxidative stress in the Korean adult population. This study also examined whether metabolic syndrome makes a difference in oxidative stress values.

This study was performed in accordance with ethical and safety guidelines upon the approval of the institutional review board in The Catholic University of Korea St. Vincent's Hospital (VC12 RISI0080).

Oxidative stress damages DNA and proteins by inducing oxidation reactions, contributing to aging, atherosclerosis, autoimmune disease, Parkinson's disease, Alzheimer's dementia, cancer, and cardiovascular disease. Overproduction and reduction of antioxidant capacity is determined by various lifestyle factors, especially non-smoking, vitamin and mineral supplements, fruit eating, and regular exercise. Male gender and aging showed negative correlations with antioxidant capacity.¹⁵⁾

In this study, the FORT values were significantly higher in the non-smoking group, non-drinking group, and females. The FORT value showed positive correlation with hs-CRP, and showed negative correlation with uric acid. Multiple linear regression analysis was performed to analyze the effects of these statistically significant variables. As a result, alcohol, smoking, and uric acid showed no significant effects. In contrast, female gender, higher hs-CRP, and metabolic syndrome showed significant relationships with higher FORT values.

However, when other variables were controlled through regression analysis, there was no significant relationship between smoking habits with FORT. Other studies such as Lorgis et al.¹⁶⁾ and Lee et al.¹⁷⁾ reported similar results. But Moller et al.¹⁸⁾ reported smoking was associated with higher oxidative stress, Vassalle et al.¹⁹⁾ reported females and smokers showed a significant relationship with increment of oxidative stress. In addition, Lesgards et al.¹⁵⁾ reported that non-smokers showed a positive relationship with antioxidant capacity.

Since tobacco has many oxidating agents such as nicotine, FORT and other oxidating agents, it can contribute to atherosclerosis.²⁰⁾ However, many studies reported varied results. Thus, additional studies are necessary to test the relationship under control.

The FORT values showed a positive correlation with hs-CRP (P ≤ 0.001). In contrast, they showed a negative correlation with uric acid (P = 0.013). However, other biochemical markers showed no significant relationship with the FORT values. Only hs-CRP was truly related to the FORT value when the analyses of the effects of various independent variables on the FORT values were examined. Hs-CRP is an inflammatory marker and it has been examined in many studies. It has been considered as a potential marker of risk of cardiovascular disease.^21,22)

Other studies reported oxidative stress as an oxidative stress marker,^23-25) and Lee et al.¹⁷⁾ reported that hs-CRP exhibited a positive correlation with the FORT value. Many other studies reported a relationship between hs-CRP and oxidative stress under controlled environments, thus, utilization of hs-CRP as an oxidative stress predictable factor could be taken into consideration. Fujita et al.²⁶⁾ reported that systemic oxidative stress, as measured by urinary 8-epi-PGF2, is strongly associated with visceral fat accumulation and metabolic syndrome. Kotani and Taniguchi²⁷⁾ reported that subjects with metabolic syndrome (n = 37) exhibited significantly higher reactive oxygen metabolites levels than those without metabolic syndrome (n = 37) in Japanese males aged under 60 years. Jialal et al.²⁸⁾ reported that nascent metabolic syndrome was associated with increased oxidative stress as demonstrated by both circulating and cellular biomarkers, which could contribute to the risk for both diabetes and cardiovascular disease. Similarly, in this study, metabolic syndrome patients exhibited significantly higher FORT values under controlled environments. In particular, higher fasting plasma glucose and higher LDL cholesterol levels exhibited significant relationships with the FORT values. Reactive oxygen species regenerate endogenous antioxidants, interrupt glucose absorption in muscles and fat cells, decrease the secretion of insulin in beta cells, and increase insulin resistance and fasting plasma glucose levels.²⁹⁾ Atherosclerosis and cardiomyopathy in type 2 diabetes are caused by insulin resistance.³⁰⁾ In addition, low HDL cholesterol levels are an important risk factor for cardiovascular disease. HDL cholesterol has many cardiovascular protection effects, such as anti-inflammatory effects, anti-oxidant capacity, anti-coagulation, and anti-thrombotic capacity.³¹⁾

Almost all females answered that they were non-smokers in self-reporting questionnaires. However, there was a report that only 7.1% of female subjects reported they are smokers but actually 13.9% of female subjects were proven to be smokers by examination of nicotine in their urine.³²⁾ According to this, self-reporting questionnaires on smoking habits have low reliability. Therefore, collection of urine to check nicotine levels or examination of expiratory CO₂ levels is one possible solution.

Second, in women, oxidative stress can be altered by menopausal state. However, this study had too few female subjects to analyze the effects of menopausal state on the FORT value. Additional large-scale studies should be conducted to examine the relationship between oxidative stress and menopausal state in Korean women.

In this study, women, individuals who had high levels of hs-CRP, and metabolic syndrome patients exhibited higher oxidative stress. There have been few domestic studies on metabolic syndrome and oxidative stress in Korea. This study provides evidence that metabolic patients have higher oxidative stress than healthy individuals. Additional prospective intervention studies should be conducted to examine whether cured metabolic syndrome patients show reduction of the FORT values.