Jean Kyung Paik

Effects of lycopene supplementation on oxidative stress and markers of endothelial function in healthy men

OBJECTIVE The objective was to determine the effects of lycopene supplementation on endothelial function assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) and oxidative stress. METHODS Healthy men (n=126) were randomized to receive placebo (n=38), 6 mg (n=41), or 15 mg (n=37) lycopene daily for 8-week. RESULTS Serum lycopene increased in a dose-dependent manner after 8-week supplementation (P<0.001). The 15 mg/day group had greater increase in plasma SOD activity (P=0.014) and reduction in lymphocyte DNA comet tail length (P=0.042) than the placebo group. Intragroup comparison revealed a 23% increase in RH-PAT index from baseline (1.45±0.09 vs. 1.79±0.12; P=0.032) in the 15 mg/day group after 8-week. hs-CRP, systolic blood pressure, sICAM-1 and sVCAM-1 significantly decreased, and β-carotene and LDL-particle size significantly increased only in the 15 mg/day group. Interestingly, the beneficial effect of lycopene supplementation on endothelial function (i.e., RH-PAT and sVCAM-1) were remarkable in subjects with relatively impaired endothelial cell function at initial level. Changes in RH-PAT index correlated with SOD activity (r=0.234, P=0.017) especially in the 15 mg lycopene/day group (r=0.485, P=0.003), lymphocyte DNA comet tail moment (r=-0.318, P=0.001), and hs-CRP (r=-0.238, P=0.011). In addition, changes in lycopene correlated with hs-CRP (r=-0.230, P=0.016) and SOD activity (r=0.205, P=0.037). CONCLUSION An increase in serum lycopene after supplementation can reduce oxidative stress which may play a role in endothelial function.

The association of specific metabolites of lipid metabolism with markers of oxidative stress, inflammation and arterial stiffness in men with newly diagnosed type 2 diabetes

Objective  To determine whether circulating metabolic intermediates are associated with inflammation, oxidative stress and arterial stiffness in men with newly diagnosed type 2 diabetes and investigate the circulating metabolic intermediates that may predict the risk of developing diabetes.

Dietary treatment with rice containing resistant starch improves markers of endothelial function with reduction of postprandial blood glucose and oxidative stress in patients with prediabetes or newly diagnosed type 2 diabetes

OBJECTIVE We aimed to evaluate whether 4-week of dietary treatment with rice containing resistant starch reduces blood glucose and oxidative stress as well as improves endothelial function. METHODS Patients with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or newly diagnosed type 2 diabetes (n = 90) were randomly assigned to either a group ingesting rice containing 6.51 g resistant starch daily or a control rice group for 4-weeks. We assessed fasting and postprandial levels of glucose and insulin, oxidative stress markers and endothelial function using reactive hyperemia peripheral arterial tonometry (RH-PAT). RESULTS The diet containing rice with resistant starch reduced fasting insulin and insulin resistance, postprandial glucose (P = 0.010) and insulin levels at 30 min, and glucose and insulin areas under the response curve after the standard meal. Rice with resistant starch also decreased urinary 8-epi-PGF(2α) and plasma malondialdehyde (MDA) and increased the RH-PAT index (P < 0.001) and total nitric oxide (NO). Postprandial changes in glucose at 60 and 120 min and areas under the glucose response curve, MDA, RH-PAT, and total NO of the test group differed significantly from those in the control even after adjusting for baseline values. Overall, changes in the RH-PAT index correlated positively with changes in total NO (r = 0.336, P = 0.003) and superoxide dismutase activity (r = 0.381, P = 0.001) and negatively with changes in MDA (r = -0.358, P = 0.002) and 8-epi-PGF(2α). CONCLUSIONS In patients with IFG, IGT or newly diagnosed type 2 diabetes, 4-weeks of dietary treatment with rice containing resistant starch was associated with improved endothelial function with reduction of postprandial glucose and oxidative stress compared with control.

FADS gene polymorphisms in Koreans: Association with ω6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease

OBJECTIVE We investigated the association of polymorphisms in FADS genes with polyunsaturated fatty acids (PUFAs) in serum phospholipids, lipid peroxides, and coronary artery disease (CAD) in Koreans. METHODS In this case-control study, CAD patients (n=756, 40-79 years) and healthy controls (n=890) were genotyped for rs174537 near FADS1 (FEN1 rs174537G>T), FADS2 (rs174575, rs2727270), and FADS3 (rs1000778). We calculated the odds ratios (ORs) for CAD risk and measured serum PUFA composition and lipid peroxide. RESULTS Among four SNPs, only rs174537G>T differed in allele frequencies between controls and CAD patients after adjustment for age, BMI, cigarette smoking, alcohol consumption, hypertension, diabetes mellitus, and hyperlipidemia (P=0.017). The minor T allele was associated with a lower risk of CAD [OR 0.75 (95%CI 0.61-0.92), P=0.006] after adjustment. rs174537T carriers had a significantly higher proportion of linoleic acid (LA, 18:2ω6), lower arachidonic acid (AA, 20:4ω6), and lower ratios of AA/dihomo-γ-linolenic acid (DGLA, 20:3ω6) and AA/LA than G/G subjects in both control and CAD groups. In the control group, 174537T carriers had significantly lower levels of total- and LDL-cholesterol, malondialdehyde, and ox-LDL. In CAD patients, rs174537T carriers showed a larger LDL particle size than G/G subjects. The proportion of AA in serum phospholipids positively correlated with LDL-cholesterol, ox-LDL, and malondialdehyde in controls and with 8-epi-prostaglandin F(2α) in both control and CAD groups. CONCLUSION The rs174537T is associated with a lower proportion of AA in serum phospholipids and reduced CAD risk, in association with reduced total- and LDL-cholesterol and lipid peroxides.

The apolipoprotein A5 -1131T > C promoter polymorphism in Koreans: association with plasma APOA5 and serum triglyceride concentrations, LDL particle size and coronary artery disease.

BACKGROUND The association between -1131T>C single nucleotide polymorphism (SNP) of the apolipoprotein A5 gene (APOA5) and hypertriglyceridemia raised the possibility that this SNP could be related to coronary artery disease (CAD) risk. Therefore, we investigated the association of this APOA5 -1131T>C SNP with circulating concentrations of APOA5, triglyceride and CAD in Koreans. METHODS CAD patients (n=741) and age-, sex-matched healthy controls (n=741) were genotyped for the APOA5 -1131T>C SNP. The main outcome measures were the odds ratio (OR) on CAD risk and lipid variables, APOA5 concentration and LDL particle size. RESULTS The presence of the minor allele at the -1131T>C SNP was associated with an increased risk of CAD [OR 1.34 (95% CI, 1.09-1.65), P=0.007] after adjusting for BMI, alcohol consumption, systolic blood pressure and diastolic blood pressure. There was an association between the APOA5 concentration and the -1131T>C genotype in controls (T/T: 245+/-7 ng/ml, T/C: 220+/-6, C/C: 195+/-12; P=0.001) and CAD patients (T/T: 218+/-8 ng/ml, T/C: 185+/-7, C/C: 169+/-12; P<0.001). Subjects with T/C or C/C in control and CAD patient groups showed higher triglyceride than those with T/T genotype. Also, the -1131T>C polymorphism was associated with LDL particle size (P=0.003), with the T/C or C/C controls having smaller size than the T/T controls. CONCLUSIONS The APOA5 -1131C allele is associated with reduced APOA5 concentration and with increased CAD risk. This is consistent with the observed association between the -1131C SNP, increased triglycerides as well as small LDL particle size.

Increased oxidative stress in normal-weight postmenopausal women with metabolic syndrome compared with metabolically healthy overweight/obese individuals

OBJECTIVE The purpose of this study was to assess whether the metabolically healthy overweight/obese phenotype is associated with decreased oxidative stress compared with normal-weight individuals with metabolic syndrome (MetS). MATERIALS/METHODS Plasma oxidized LDL (ox-LDL) and urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) were analyzed in a cross-sectional study of 1846 healthy postmenopausal women. Participants were classified by presence (n=569) or absence (n=1277) of MetS and by BMI (18.5-24.9kg/m(2)=normal weight, n=1254; ≥25kg/m(2)=overweight/obese, n=592). MetS was diagnosed with the modified National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS Compared to normal weight women with MetS (n=296), metabolically healthy overweight/obese women (n=319) showed lower blood pressure, triglyceride, and glucose and higher HDL cholesterol, adiponectin, and LDL particle size. Ox-LDL was higher in overweight/obese women without MetS than in normal weight women without MetS (n=958) but was lower than in women with MetS. Urinary 8-epi-PGF2α level was about 11% lower in women without MetS than in women with MetS. Normal weight women with MetS had greater odds of having ox-LDL (multivariate odds ratio [OR] 2.42, 95% CI: 1.65-3.55) and 8-epi-PGF2α (OR 1.49; CI: 1.03-2.14) levels in the top quartile compared to normal weight women without MetS after adjusting for age, drinking, smoking, total- and LDL-cholesterol, and high sensitivity C-reactive protein. Additionally, there was no significant correlation between ox-LDL and 8-epi-PGF2α. CONCLUSIONS The metabolically healthy overweight/obese phenotype was associated with a better overall metabolic profile and less oxidative stress than that observed in normal weight individuals with MetS. Furthermore, there was a lack of association between ox-LDL and 8-epi-PGF2α.

Influence of Adiponectin Gene Polymorphisms on Adiponectin Level and Insulin Resistance Index in Response to Dietary Intervention in Overweight-Obese Patients With Impaired Fasting Glucose or Newly Diagnosed Type 2 Diabetes

OBJECTIVE The aim of this study was to determine the effect of common adiponectin gene polymorphisms on dietary intervention-mediated changes in adiponectin levels and homeostasis model assessment of insulin resistance (HOMA-IR) indexes. RESEARCH DESIGN AND METHODS A total of 363 subjects with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes followed a dietary intervention (replacement of cooked refined rice with whole grains and an increase in vegetable intake) and regular walking for 12 weeks without any medication. Adiponectin gene single nucleotide polymorphisms (SNPs) (45, 276, and −11377) were examined in these subjects. RESULTS After this dietary intervention, fasting glucose levels decreased in all three SNP 45T>G genotype groups. Subjects with the SNP 45TT genotype showed increased adiponectin levels and decreased HOMA-IR indexes. Haplotype analysis revealed that homozygous carriers of the TG haplotype (45TT and 276GG) and heterozygous carriers of the TG haplotype (TG/X) showed a reduction in the HOMA-IR index after adjustment for baseline levels. Significant differences were observed in changes in HOMA-IR indexes and adiponectin concentrations according to the 45-276 TG haplotype in overweight-obese, but not in normal-weight subjects: the greatest decrease in HOMA-IR indexes and the greatest increase in adiponectin levels were shown in overweight-obese subjects with the TG/TG haplotype. CONCLUSIONS ADIPOQ genetic variants can affect circulating adiponectin levels and insulin resistance indexes in subjects with IFG or newly diagnosed type 2 diabetes in response to dietary intervention.

Effects of Nattokinase on Blood Pressure: A Randomized, Controlled Trial

The objective of this study was to examine the effects of nattokinase supplementation on blood pressure in subjects with pre-hypertension or stage 1 hypertension. In a randomized, double-blind, placebo-controlled trial, 86 participants ranging from 20 to 80 years of age with an initial untreated systolic blood pressure (SBP) of 130 to 159 mmHg received nattokinase (2,000 FU/capsule) or a placebo capsule for 8 weeks. Seventy-three subjects completed the protocol. Compared with the control group, the net changes in SBP and diastolic blood pressure (DBP) were −5.55 mmHg (95% confidence interval [CI], −10.5 to −0.57 mmHg; p <0.05) and −2.84 mmHg (CI, −5.33 to −0.33 mmHg; p >0.05), respectively, after the 8-week intervention. The corresponding net change in renin activity was −1.17 ng/mL/h for the nattokinase group compared with the control group (p <0.05). In conclusion, nattokinase supplementation resulted in a reduction in SBP and DBP. These findings suggest that increased intake of nattokinase may play an important role in preventing and treating hypertension.

Mild weight loss reduces inflammatory cytokines, leukocyte count, and oxidative stress in overweight and moderately obese participants treated for 3 years with dietary modification

Obesity-induced oxidative stress and inflammation are involved in the pathogenesis of cardiovascular disease. We investigated whether diet-induced, long-term, mild weight loss improved proinflammatory cytokine levels, leukocyte count, and oxidative stress. Overweight/obese participants (25 ≤ body mass index < 34 kg/m(2), N = 122, 30-59 years) joined a 3-year-long clinical intervention involving daily 100-kcal calorie deficits. Successful weight loss was defined as a reduction in initial body weight equal to 2 kg after the clinical intervention period. Body weight in the successful mild weight loss group (SWL, n = 50) changed 5.4% (-4.16 ± 0.31 kg) compared to 0.05 ± 0.14 kg in the unsuccessful weight loss group (n = 49). After 3 years, SWL participants exhibited significantly reduced insulin, triglycerides, total and low-density lipoprotein cholesterol, free fatty acids, and leukocyte count (P = .030). Furthermore, in the SWL group, serum interleukin (IL)-1β, IL-6, and urinary 8-epi-prostaglandin (PG)F2α were significantly reduced (45%, 30%, and 14%, respectively). In contrast, the unsuccessful weight loss group exhibited significant increases in percentage of body fat, waist circumference, oxidized low-density lipoprotein, and tumor necrosis factor-α, as well as a significant decrease in high-density lipoprotein cholesterol. After adjusting for baseline values, the 2 groups demonstrated significantly different percentage of body fat, waist circumference, leukocyte count (P = .018), insulin, IL-6 (P = .031), IL-1β (P < .001), and tumor necrosis factor-α (P < .001), as well as urinary 8-epi-PGF2α (P = .036). A positive correlation existed between IL-1β and urinary 8-epi-PGF2α (r = 0.435, P < .001) and between changes in IL-6 and urinary 8-epi-PGF2α (r = 0.393, P < .001). Long-term mild weight loss reduces inflammatory cytokine levels, leukocyte counts, and oxidative stress and may reverse the elevated oxidative stress induced by inflammatory mediators in the overweight and obese.

Association of apolipoprotein A5 concentration with serum insulin and triglyceride levels and coronary artery disease in Korean men

OBJECTIVE Whereas the relation between apolipoprotein A5 (APOA5) gene polymorphisms and triglycerides (TG) levels is well established, the associations between apoA5 concentrations, TG and coronary artery disease (CAD) remain controversial. Therefore, we investigated these relations in the setting of a case-control study involving Korean males. METHODS ApoA5, TG, insulin, free fatty acid (FFA) and lipoprotein profiles were determined using a cross-sectional design in 777 healthy controls and 367 CAD patients. RESULTS Plasma apoA5 concentration was lower in CAD patients than controls (192.7+/-5.2 vs. 237.2+/-3.7ng/ml, P<0.001). Values in the second and top tertiles of apoA5 were associated with a decreased odds ratio (OR) for CAD when compared with values in the bottom tertile; OR for apoA5 top tertile was 0.33 (95% CI, 0.23-0.47) in the age- and BMI-adjusted model and 0.35 (95% CI, 0.23-0.56) following additional adjustments for smoking, drinking status, blood pressure, TG and HDL-cholesterol. After adjustment for age and BMI, plasma apoA5 concentration was negatively correlated with serum TG (r=-0.188, P<0.001) and insulin (r=-0.185, P<0.001) in normotriglyceridemic controls (TG<150mg/dL, n=509) whereas apoA5 was positively correlated with serum TG in hypertriglyceridemic controls (TG> or =150mg/dL, n=268) (r=0.246, P<0.001) and total CAD patients (r=0.177, P<0.01). Regardless of TG levels and CAD status, apoA5 concentration was positively correlated with HDL-cholesterol and FFA levels. CONCLUSIONS Our data supports an inverse association between plasma apoA5 concentrations and CAD risk, probably due to the observed negative correlations of apoA5 with TGs and insulin, although these correlations were affected by TG levels.