Traditional japanese diet score and the sustainable development goals by a global comparative ecological study.

BACKGROUND: Reducing the environmental impact of the food supply is important for achieving Sustainable Development Goals (SDGs) worldwide. Previously, we developed the Traditional Japanese Diet Score (TJDS) and reported in a global ecological study that the Japanese diet is associated with reducing obesity and extending healthy life expectancy etc. We then examined the relationship between the TJDS and environmental indicators. METHODS: The average food (g/day/capita) and energy supplies (kcal/day/capita) by country were obtained from the Food and Agriculture Organization of the United Nations Statistics Division database. The TJDS was calculated from eight food groups (beneficial food components in the Japanese diet: rice, fish, soybeans, vegetables, and eggs; food components that are relatively unused in the traditional Japanese diet: wheat, milk, and red meat) by country using tertiles, and calculated the total score from - 8 to 8, with higher scores meaning greater adherence to the TJDS. We used Land Use (m2), Greenhouse gas (GHG) emissions 2007/2013 (kg CO2eq), Acidifying emissions (g SO2eq), Eutrophying emissions (g PO43- eq), Freshwater (L), and water use (L) per food weight by Poore et al. as the environmental indicators and multiplied these indicators by each country's average food supply. We evaluated the cross-sectional and longitudinal associations between the TJDS and environmental indicators from 2010 to 2020. This study included 151 countries with populations ≥ 1 million. RESULTS: Land use (ß ± standard error; -0.623 ± 0.161, p < 0.001), GHG 2007 (-0.149 ± 0.057, p < 0.05), GHG 2013 (-0.183 ± 0.066, p < 0.01), Acidifying (-1.111 ± 0.369, p < 0.01), and Water use (-405.903 ± 101.416, p < 0.001) were negatively associated with TJDS, and Freshwater (45.116 ± 7.866, p < 0.001) was positively associated with TJDS after controlling for energy supply and latitude in 2010. In the longitudinal analysis, Land Use (ß ± standard error; -0.116 ± 0.027, p < 0.001), GHG 2007 (-0.040 ± 0.010, p < 0.001), GHG 2013 (-0.048 ± 0.011, p < 0.001), Acidifying (-0.280 ± 0.064, p < 0.001), Eutrophying (-0.132 ± 0.062, p < 0.05), and Water use (-118.246 ± 22.826, p < 0.001) were negatively associated with TJDS after controlling for confounders. CONCLUSIONS: This ecological study suggests that the traditional Japanese dietary pattern might improve SDGs except Fresh water.

The Global Association between Egg Intake and the Incidence and Mortality of Ischemic Heart Disease-An Ecological Study.

The relationship between egg consumption and ischemic heart disease (IHD) remains controversial as there is still no clear answer regarding the relationship, with research limited to a few geographical regions. In the current study, we conducted a longitudinal analysis of the association between egg intake and IHD incidence (IHDi) and mortality (IHDd) using 28 years of international data from 1990 to 2018. Egg intake (g/day/capita) by country was obtained from the Global Dietary Database. Age-standard IHDi and IHDd rates per 100,000 subjects in each country were obtained from the 2019 Global Burden of Disease database. The analysis included a total of 142 countries with populations of at least one million, for which all data were available from 1990 to 2018. Eggs are consumed worldwide, and regional differences in consumption are also shown. Utilizing IHDi and IHDd as objective variables and egg intake as an explanatory variable, the analysis was conducted using linear mixed models, which controlled for inter- and intra-country variation from year to year. The results showed a significant negative association between egg intake, and IHDi (-0.253 ± 0.117, p < 0.05) and IHDd (-0.359 ± 0.137, p < 0.05). The analysis was carried out using R 4.0.5. The results suggest that adequate egg intake might suppress IHDi and IHDd on a global scale.

Global Association between Traditional Japanese Diet Score and All-Cause, Cardiovascular Disease, and Total Cancer Mortality: A Cross-Sectional and Longitudinal Ecological Study.

OBJECTIVE: Studies conducted on Japanese people have suggested that a traditional Japanese diet contributes to good health, longevity, and protection against several non-communicable diseases. However, it is unknown whether traditional Japanese dietary patterns are associated with all-cause mortality, cardiovascular disease, and cancer mortality globally. The purpose of this cross-sectional and longitudinal ecological study is to clarify the global association between the traditional Japanese diet score (TJDS) and all-cause, cardiovascular disease, and total cancer mortality. METHODS: Data on food supply and all-cause mortality, cardiovascular disease mortality, total cancer mortality, and covariables by country were obtained from a relevant internationally available database. TJDS by country was calculated from eight food groups and the total score ranged from -8 to 8, with higher scores indicating greater adherence to a traditional Japanese diet. We evaluated the cross-sectional and 10-year longitudinal association between TJDS and all-cause, cardiovascular disease, and total cancer mortality using 2009 as the baseline in 142 countries with populations of more than one million. A cross-sectional analysis and a longitudinal analysis were performed using three general linear models or three linear mixed models with different covariables. RESULTS: In cross-sectional models controlled for fully-adjusted covariables, TJDS was negatively associated with all-cause mortality (ß ± standard error; -43.819 ± 11.741, p < 0.001), cardiovascular disease mortality (-22.395 ± 4.638, p < 0.001), and total cancer mortality (-3.893 ± 1.048, p < 0.001). In 10-year longitudinal models controlled for fully-adjusted covariables, TJDS was significantly negatively associated with all-cause mortality (-31.563 ± 7.695, p < 0.001), cardiovascular disease mortality (-16.249 ± 4.054, p < 0.001), and total cancer mortality (-3.499 ± 0.867, p < 0.001). CONCLUSIONS: This cross-sectional and longitudinal ecological study suggests that the traditional Japanese diet is associated with lower all-cause mortality, cardiovascular disease mortality, and total cancer mortality, worldwide.

Change in the association between coffee intake and ischemic heart disease in an international ecological study from 1990 to 2018.

In previous observational studies, the association between coffee intake and risk of cardiovascular disease has reversed from positive to negative over time. This long-term international ecological study examined whether the association between coffee intake and mortality and incidence rates of ischemic heart disease (IHD) changed between 1990 and 2018 using multiple coherent data. We obtained data on coffee intake per capita, IHD mortality and incidence rates per 100,000 population, and socioeconomic and lifestyle indicators for each country from various publicly available databases. We integrated and analyzed data from 147 countries with populations of ≥ 1 million. We employed a linear mixed model analysis to assess the association between coffee intake and IHD mortality and incidence rates by year. The mean global coffee intake increased (p < 0.001), whereas IHD mortality (p < 0.001) and incidence (p = 0.073) decreased. In all models, the interaction between coffee intake and year showed a significant inverse association for IHD mortality and incidence rates (p < 0.001 for all). The country-level association between coffee intake and IHD mortality and incidence rates between 1990 and 2018 was stronger in the negative direction.

Regular egg consumption at breakfast by Japanese woman university students improves daily nutrient intakes: open-labeled observations.

BACKGROUND AND OBJECTIVES: Eggs, an important source of high-quality protein, contain a variety of key nutrients and antioxidants. Here we conducted an intervention study to evaluate whether the additional consumption of one egg per day would affect the daily nutritional intakes and blood antioxidant status in Japanese woman university students. METHODS AND STUDY DESIGN: For 4 weeks, the 14 subjects were provided a nutritious breakfast including one boiled egg, and they were asked to keep a daily dietary record. RESULTS: The subjects' daily energy intake during the intervention did not differ compared to the baseline, whereas the protein energy ratio and cholesterol intake were significantly increased. The subjects' consumption of confectionery during the intervention was significantly decreased compared to the pre-trial period. The total score of adherence to the food-based Japanese dietary guidelines for a healthy diet during the intervention was higher than that at baseline. The analysis of fasting blood samples showed that the subjects' serum lipids levels were not altered, whereas their malondialdehyde modified low-density lipoprotein (MDA-LDL) levels and the oxidative susceptibility of LDL were significantly reduced after the intervention. More importantly, serum folic acid levels were significantly increased. CONCLUSIONS: Our results suggest that regular egg consumption at breakfast can help improve the daily nutritional status and dietary habits and also ameliorate certain indices of antioxidant status in young women.

Low Plasma Levels of Fibroblast Growth Factor-21 in Patients with Peripheral Artery Disease.

AIM: Fibroblast growth factor-21 (FGF-21) is a metabolic regulator with beneficial effects on glucolipid metabolism. Since FGF-21 has lipid-lowering, anti-inflammatory and anti-oxidant properties, it may play a protective role against atherosclerosis. However, blood FGF-21 levels in coronary artery disease (CAD) or peripheral artery disease (PAD) have not been elucidated. METHODS: We measured plasma FGF-21 levels in 417 patients undergoing coronary angiography, who also had ankle-brachial index test for PAD screening. RESULTS: CAD was found in 224 patients (1-vessel [1-VD], n=92; 2-vessel [2-VD], n=65; 3-vessel disease [3-VD], n=67). No significant difference was found in the FGF-21 levels between 224 patients with CAD and 193 without CAD (median 26.0 vs. 25.9 pg/mL). FGF-21 levels in 4 groups of CAD(-), 1-VD, 2-VD, and 3-VD were 25.9, 37.2, 19.4, and 0.0 pg/mL. FGF-21 tended to be highest in 1-VD and lowest in 3-VD, but the difference did not reach statistical significance. PAD was found in 38 patients. Compared to the 379 patients without PAD, 38 with PAD had CAD more often (87% vs. 50%), especially 3-VD (P＜0.001). FGF-21 levels were lower in patients with PAD than in those without PAD (0.0 vs. 30.7 pg/mL, P＜0.02). In multivariate analysis, the FGF-21 level was an independent factor for PAD, but not for CAD. Odds ratio for PAD was 2.13 (95%CI=1.01-4.49) for a low FGF-21 level (＜15.6 pg/mL). CONCLUSION: No significant difference was found in the FGF-21 levels between patients with and without CAD. However, FGF-21 levels were low in patients with PAD, and were a factor for PAD independent of atherosclerotic risk factors.

Plasma interleukin-27 levels in patients with coronary artery disease.

Interleukin (IL)-27, one of cytokines in the IL-12 family, is considered to have both pro- and anti-inflammatory properties. However, blood IL-27 levels in coronary artery disease (CAD) have not been fully elucidated yet. This cross-sectional study was done to elucidate the association between blood IL-27 levels and CAD.We investigated plasma IL-27 and high-sensitivity C-reactive protein (hsCRP) levels in 274 consecutive patients who underwent elective coronary angiography for suspected CAD. CAD was present in 177 patients [30 acute coronary syndrome (ACS) and 147 stable CAD]. Compared with 97 patients without CAD, 177 patients with CAD had higher IL-27 (median 0.26 vs 0.22 ng/mL, P < .05) and higher hsCRP (0.98 vs 0.41 mg/L, P < .001) levels. However, there was no significant difference in IL-27 levels among 3 groups of ACS, stable CAD, and CAD(-) (0.26, 0.25, and 0.22 ng/mL), whereas hsCRP levels were significantly higher in ACS and stable CAD than in CAD(-) (2.09, 0.91 vs 0.41 mg/L, P < .001) and were highest in ACS. IL-27 levels tended to increase with the number of >50% stenotic coronary vessels: 0.22 in CAD(-), 0.22 in 1-vessel disease, 0.31 in 2-vessel disease, and 0.27 ng/mL in 3-vessel disease (P < .05). A stepwise increase in hsCRP levels was also found: 0.41 in CAD(-), 0.75 in 1-vessel, 1.05 in 2-vessel, and 1.85 mg/L in 3-vessel disease (P < .001). Plasma hsCRP levels significantly (r = 0.35), but IL-27 levels weakly (r = 0.15), correlated with the number of stenotic coronary segments. In multivariate analysis, both IL-27 and hsCRP levels were independent factors associated with CAD. However, hsCRP, but not IL-27, was also a factor for ACS.While plasma IL-27 levels were high in patients with CAD, these levels were an independent factor for only CAD, not ACS, and weakly correlated with the severity of CAD. Our results suggest that IL-27 is unlikely to be a good biomarker reflecting the severity of CAD or the presence of ACS, or to play a major role in the progression of CAD.

Additional consumption of one egg per day increases serum lutein plus zeaxanthin concentration and lowers oxidized low-density lipoprotein in moderately hypercholesterolemic males.

The egg is a nutrient-dense food and contains antioxidative carotenoids, lutein and zeaxanthin, but its impact on serum cholesterol levels has been a matter of concern, especially for individuals who have high serum cholesterol levels. We conducted this study to determine whether and how the daily additional consumption of one egg affects serum lipid profiles and parameters of LDL oxidation in moderately hypercholesterolemic males. Nineteen male Japanese adults (total cholesterol [TC]>5.2mmol/L) participated, consuming one soft boiled egg per day for 4weeks in addition to their habitual diet. Despite the significant increase in their intake of dietary cholesterol during the intervention period, the subjects' serum concentrations of TC and low-density lipoprotein cholesterol (LDL-C) did not increase. Their serum malondialdehyde modified low-density lipoprotein (MDA-LDL) concentrations were significantly decreased and their LDL oxidation lag times, reflecting the resistance of free-radical-induced LDL lipid peroxidation (ex vivo), was prolonged after 2 and 4weeks. At weeks 2 and 4, the subjects' serum lutein+zeaxanthin concentrations were significantly higher than their baseline values and showed both an inverse relation with MDA-LDL and a positive relationship with the LDL oxidation lag time. These data showed that in moderately hypercholesterolemic males, the additional consumption of one egg per day for 4weeks did not have adverse effects on serum TC or LDL-C, and it might reduce the susceptibility of LDL to oxidation through an increase in the serum lutein and zeaxanthin concentrations.

Plasma Soluble Endoglin Levels Are Inversely Associated With the Severity of Coronary Atherosclerosis-Brief Report.

OBJECTIVE: Transforming growth factor-ß inhibits migration and proliferation of endothelial and smooth muscle cells. Endoglin is a transmembrane receptor for transforming growth factor-ß1 and transforming growth factor-ß3. Endoglin is released into blood as a soluble form (soluble endoglin [sEng]), but plasma sEng levels in patients with coronary artery disease (CAD) have not been elucidated. APPROACH AND RESULTS: We measured plasma sEng levels in 244 patients undergoing coronary angiography. The severity of coronary atherosclerosis was evaluated as the numbers of >50% stenotic vessels and segments. CAD was found in 147 patients, of whom 55 had 1-vessel, 42 had 2-vessel, and 50 had 3-vessel disease. Compared with 97 patients without CAD, 147 with CAD had lower sEng levels (median 4.04 versus 4.37 ng/mL; P<0.005). A stepwise decrease in sEng levels was found based on the number of stenotic vessels: 4.37 in CAD(-), 4.23 in 1-vessel, 4.13 in 2-vessel, and 3.74 ng/mL in 3-vessel disease (P<0.005). sEng levels inversely correlated with the number of stenotic segments (r=-0.25; P<0.001). In multivariate analysis, sEng was an independent factor for 3-vessel disease and CAD. Odds ratios for CAD and 3-vessel disease were 0.97 (95% confidence interval, 0.95-0.99; P<0.02) and 0.96 (95% confidence interval, 0.93-0.99; P<0.01) for a 0.1 ng/mL increase in sEng levels, respectively. CONCLUSIONS: Plasma sEng levels were low in patients with CAD, especially 3-vessel disease, and were inversely associated with the severity of coronary atherosclerosis.

The Effect of the Consumption of Egg on Serum Lipids and Antioxidant Status in Healthy Subjects.

The egg is a nutrient-dense food and contains a number of antioxidants. The consumption of eggs has been considered to improve the balance of diets, although its impact on serum cholesterol levels has been a matter of concern in many countries. Here, we conducted a pilot study to investigate whether daily additional consumption of an egg might affect serum lipid profiles and also antioxidant status in healthy subjects. Fourteen male subjects were provided with breakfasts including a boiled egg for 4 wk. At the end of intervention, serum concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were unchanged, despite the significant increase in the intake of dietary cholesterol. In contrast, a significant increase in high-density lipoprotein cholesterol (HDL-C) and a reduction of the LDL-C/HDL-C ratio were observed. Interestingly, the malondialdehyde modified-LDL (MDA-LDL)/LDL-C ratio and the oxidizability of LDL were significantly reduced. Serum total antioxidant capacity value after the intervention period was higher than at baseline. These data indicate that consuming one egg per day for 4 wk as breakfast in addition to a normal diet does not affect serum lipids, and suggests that it may improve serum antioxidant status in healthy males.

Terminalia bellirica Extract Inhibits Low-Density Lipoprotein Oxidation and Macrophage Inflammatory Response in Vitro.

The deciduous tree Terminalia bellirica found in Southeast Asia is extensively used in traditional Indian Ayurvedic medicine for the treatment of hypertension, rheumatism, and diabetes. The anti-atherogenic effect of Terminalia bellirica fruit has not been fully elucidated. Here, we investigated the effect of Terminalia bellirica extract (TBE) on low-density lipoprotein (LDL) oxidation and inflammation in macrophages. TBE showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (EC50: 7.2 ± 1.2 µg/mL) and 15-lipoxygenase inhibitory activity. TBE also significantly inhibited free radical-induced LDL oxidation compared to the solvent control in vitro. In THP-1 macrophages, TBE treatment resulted in significant decreases of the mRNA expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and lectin-like oxidized LDL receptor-1 (LOX-1). TBE also reduced matrix metalloproteinase (MMP)-9 secretion and intracellular reactive oxygen species (ROS) production in THP-1 macrophages. These results show that TBE has the inhibitory effects on LDL oxidation and macrophage inflammatory response in vitro, suggesting that its in vivo use might inhibit atherosclerosis plaque progression.

Green tea catechins prevent low-density lipoprotein oxidation via their accumulation in low-density lipoprotein particles in humans.

Green tea is rich in polyphenols, including catechins which have antioxidant activities and are considered to have beneficial effects on cardiovascular health. In the present study, we investigated the effects of green tea catechins on low-density lipoprotein (LDL) oxidation in vitro and in human studies to test the hypothesis that catechins are incorporated into LDL particles and exert antioxidant properties. In a randomized, placebo-controlled, double-blind, crossover trial, 19 healthy men ingested green tea extract (GTE) in the form of capsules at a dose of 1 g total catechin, of which most (>99%) was the gallated type. At 1 hour after ingestion, marked increases of the plasma concentrations of (-)-epigallocatechin gallate and (-)-epicatechin gallate were observed. Accordingly, the plasma total antioxidant capacity was increased, and the LDL oxidizability was significantly reduced by the ingestion of GTE. We found that gallated catechins were incorporated into LDL particles in nonconjugated forms after the incubation of GTE with plasma in vitro. Moreover, the catechin-incorporated LDL was highly resistant to radical-induced oxidation in vitro. An additional human study with 5 healthy women confirmed that GTE intake sufficiently increased the concentration of gallated catechins, mainly in nonconjugated forms in LDL particles, and reduced the oxidizability of LDL. In conclusion, green tea catechins are rapidly incorporated into LDL particles and play a role in reducing LDL oxidation in humans, which suggests that taking green tea catechins is effective in reducing atherosclerosis risk associated with oxidative stress.

Estimated Dietary Polyphenol Intake and Major Food and Beverage Sources among Elderly Japanese.

Estimating polyphenol intake contributes to the understanding of polyphenols' health benefits. However, information about human polyphenol intake is scarce, especially in the elderly. This study aimed to estimate the dietary intake and major sources of polyphenols and to determine whether there is any relationship between polyphenol intake and micronutrient intake in healthy elderly Japanese. First, 610 subjects (569 men, 41 women; aged 67.3 ± 6.1 years) completed food frequency questionnaires. We then calculated their total polyphenol intake using our polyphenol content database. Their average total polyphenol intake was 1492 ± 665 mg/day, the greatest part of which was provided by beverages (79.1%). The daily polyphenol intake differed largely among individuals (183-4854 mg/day), also attributable mostly to beverage consumption. Coffee (43.2%) and green tea (26.6%) were the major sources of total polyphenol; the top 20 food items accounted for >90%. The polyphenol intake did not strongly correlate with the intake of any micronutrient, suggesting that polyphenols may exert health benefits independently of nutritional intake. The polyphenol intake in this elderly population was slightly higher than previous data in Japanese adults, and beverages such as coffee and green tea contributed highly to the intake.

Polyphenol Intake from Beverages in Japan over an 18-Year Period (1996-2013): Trends by Year, Age, Gender and Season.

An association between the dietary intake of polyphenols and human health has been shown in many epidemiological studies. Since beverages are rich sources of polyphenols, we aimed to evaluate the polyphenol intake from beverages in Japanese individuals with a focus on differences according to year, age, gender and season. More than 10,000 Japanese male and female subjects aged 1-99 y old participated in this survey every year from 1996 to 2013, and their beverage consumption and amount of polyphenol intake were calculated. Polyphenol intake from beverages in Japan showed no tendency to increase or decrease over the 18-y period, and the major sources of polyphenols in Japanese daily life were coffee and green tea. Polyphenol intake was larger in participants with higher age up to 59 y old in both male and female subjects. There was a slight difference in polyphenol intake by gender, with adult males consuming more polyphenols than adult females. Polyphenols were consumed slightly more in the winter than the summer, although the seasonal difference in polyphenol intake was not large. Our results suggest that polyphenol intake from beverages is influenced by age rather than gender or season in Japan, and may not have changed over time, at least over the 18-y period beginning in 1996 in Japan.

Pine bark extract prevents low-density lipoprotein oxidation and regulates monocytic expression of antioxidant enzymes.

Polyphenols are widely distributed in leaves, seeds, bark, and flowers and considered to have beneficial effects on cardiovascular health. We hypothesized that the potent antioxidant properties of pine bark extract (PBE) are exerted by its ability to scavenge free radicals and induce antioxidant enzymes. Therefore, we investigated the effects of PBE on low-density lipoprotein (LDL) oxidation and the antioxidant defense system in monocytes. Oxidative susceptibility of LDL was determined by lag time assay in vitro and by using a human umbilical vein endothelial cell-mediated oxidation model. THP-1 monocytic cells were treated with PBE, and the expression of antioxidant enzymes was measured by real-time polymerase chain reaction and Western blot. Pine bark extract showed radical scavenging ability and significantly inhibited free radical-induced and endothelial cell-mediated LDL oxidation in vitro. Pine bark extract treatment resulted in increases in the expressions of antioxidant enzymes, glutathione peroxidase-1, catalase, and heme oxygenase-1 in THP-1 cells. In addition, PBE induced nuclear factor-erythroid-2-related factor 2 activation, which was accompanied by the activation of extracellular signal-regulated kinase and Akt despite a down-regulation of reactive oxygen species. After the monocyte investigations, we further examined the antioxidant effect after the intake of PBE by 10 healthy male volunteers. Pine bark extract significantly prolonged the lag time of LDL oxidation. Based on our findings, it appears that PBE enhances the antioxidant defense capacity of LDL and monocytes and may play a preventive role in atherosclerosis progression.

Coffee and beverages are the major contributors to polyphenol consumption from food and beverages in Japanese middle-aged women.

Food and beverages rich in polyphenols have been shown to reduce the risk of non-communicable diseases. The present study estimated polyphenol levels and consumption from food and beverages in Japanese women. Randomly recruited housewives living in the area around Tokyo (n 109; aged 21-56 years; Group 1) recorded all beverages and foods they ingested for 7 d, and the total polyphenol (TP) consumption was estimated based on the TP content of each item measured with a modified Folin-Ciocalteu method. For Group 1, TP was consumed at 841 (sd 403) mg/d (range 113-1759 mg/d), and beverages were a larger source of TP (79 %) than food (21 %). The largest single source of TP was coffee at 47 %, followed by green tea, black tea, chocolate, beer and soya sauce, at 16, 5·7, 3·3, 3·2 and 3·1 %, respectively. In terms of food groups, cereals/noodles, vegetables, fruits, beans and seeds, and seasonings (except for soya sauce) contributed 5·0, 4·0, 1·4, 1·8 and 2·4 %, respectively. Another group of housewives who consumed at least one cup of coffee per d were separately recruited (n 100; Group 2) in the same area. Their consumption of TP was higher at 1187 (sd 371) mg/d (range 440-2435 mg/d) than Group 1 (P < 0·001), and the difference mostly came from the coffee consumption. We conclude that not food but beverages, especially coffee, may be the major contributor to TP consumption in Japanese women.

Antioxidant activities of Perilla frutescens against low-density lipoprotein oxidation in vitro and in human subjects.

Perilla (Perilla frutescens (L.) Britt.) is a popular food as well as a traditional medicine in Japan, China, and other Asian countries. The aim of this study was to investigate the inhibitory effects of perilla on low-density lipoprotein (LDL) oxidation in vitro and in human subjects. We compared the antioxidant activities of red perilla and green perilla. Both green and red perilla had high 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities and were abundant in polyphenol compounds. In addition, the radical scavenging activity and polyphenol content of red perilla were higher than those of green perilla. Perilla dramatically inhibited azo-radical-induced LDL oxidation and endothelial-cell-mediated LDL oxidation in vitro. Moreover, red perilla significantly increased mRNA and protein expression levels of antioxidant enzymes in endothelial cells. We further examined the antioxidant effects against LDL in human subjects after the consumption of perilla extracts. After oral intake of red perilla, the subjects' LDL oxidation lag times were significantly longer than those before the intake. Furthermore, lipid peroxide formation and the electrophoretic mobility of LDL decreased markedly. These results suggested that perilla, especially the red variety, had high antioxidant activity and prevented the oxidation of LDL, which is a process strongly related to the development of atherosclerosis.