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Annals of Internal Medicine | 2006

The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults.

Hiroyasu Iso; Chigusa Date; Kenji Wakai; Mitsuru Fukui; Akiko Tamakoshi

Context Caffeine intake from coffee has been associated with a lower incidence of diabetes. Researchers have not studied the relationship of green tea, a popular beverage in Japan, where the incidence of diabetes is increasing rapidly. Contributions The authors estimated the intake of caffeine-containing beverages in a community-based survey in Japan and measured the 5-year incidence of diabetes. Greater intake of green tea or coffee was associated with a reduced incidence of diabetes. The effect of green tea was largely observed in women, was dose-related, and reflected caffeine intake. Implications Higher intake of caffeine, whether from coffee or green tea, is associated with a lower incidence of diabetes. The Editors The prevalence of type 2 diabetes has increased worldwide, particularly in Asian countries where it was previously low (1). In Japan, population-based studies have shown a 2-fold increase in the prevalence of diabetes during the past 2 decades, from 5% to 10% to 10% to 15% (2). Several cohort studies done in Europe and in the United States reported an association between coffee consumption, a major source of caffeine, and reduced risk for diabetes (3-7). Although these studies did not show any association between consumption of black tea and the risk for diabetes, they did not examine the effect of green or oolong teas, major sources of caffeine in Asian countries. Consumption of green tea is common in Japan; 80% of the population drinks green tea, and the average consumption per capita is 2 cups per day (8). We wanted to determine whether there is a relationship between consumption of green tea and the risk for type 2 diabetes and, if so, whether caffeine fully accounts for this relationship. To examine these questions, we analyzed data from a large cohort study of 19487 middle-aged men and women in 25 communities across Japan. We also examined the effect of age, sex, body mass index (BMI), family history, smoking status, alcohol use, magnesium intake, and physical activity on the association between this mode of caffeine consumption and risk for diabetes. Methods The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) started between 1988 and 1990. A total of 110792 individuals (46465 men and 64327 women) who were 40 to 79 years of age and living in 45 communities across Japan participated in municipal health screening examinations and completed self-administered questionnaires regarding lifestyle and medical history of cardiovascular disease and cancer (9). Informed consent was obtained before the completion of the questionnaire. Participants from 25 of the 45 communities completed 5-year follow-up surveys. Among 35690 participants (15177 men and 20513 women) who were 40 to 65 years of age at baseline without a history of type 2 diabetes, stroke, coronary heart disease, or cancer, 17413 individuals (49%; 6727 men and 10686 women) completed the 5-year follow-up questionnaire and provided valid responses on tea or coffee consumption and history of type 2 diabetes. The data from these 17413 individuals were used for the analyses. The mean age of the nonrespondents was 1 year younger for men (52.3 vs. 53.3 years of age) and did not differ for women (53.1 vs. 53.0 years of age) compared with the respondents. The mean BMI and the prevalence of a BMI of 25.0 kg/m2 or greater did not differ between the respondents and nonrespondents. Mean BMI was 22.7 kg/m2 versus 22.8 kg/m2 for men and 22.8 kg/m2 versus 22.9 kg/m2 for women, respectively; the prevalence of overweight was 18% versus 19% for men and 21% versus 22% for women, respectively. The ethical committees at Nagoya University and the University of Tsukuba approved the study. Assessment of Consumption of Tea and Coffee and Caffeine Intake At baseline, consumption of tea and coffee was assessed by using a self-administered dietary questionnaire. Participants were asked to state their average consumption of green tea, black tea, oolong tea, and coffee during the previous year. They could select any of 4 frequency responses: less than once a week, about 1 to 2 times a week, about 3 to 4 times a week, and almost every day. Participants who selected the response of almost every day were also asked to state their average consumption of these beverages in number of cups per day. We classified the categories of consumption as less than 1 cup per week, 1 to 6 cups per week, 1 to 2 cups per day, 3 to 5 cups per day, and 6 or more cups per day. The highest 2 or 3 consumption categories were combined for coffee, black tea, and oolong tea because of the small number of participants in these categories. The consumption of decaffeinated coffee or tea was not recorded because these products were not commercially available in Japan in the early 1990s. The total intake of caffeine was calculated by adding the caffeine content from each specific beverage (1 cup for coffee or tea) and multiplying it by the participants weight proportional to the frequency of caffeine use. We estimated the size of the cup for each beverage from a validation study (10) and the caffeine content per 100 mL of each beverage from the Japan Food Tables (11). The estimated caffeine content was 153 mg per cup (170 mL) of coffee, 30 mg per cup (200 mL) of green tea, 51 mg per cup (170 mL) of black tea, and 38 mg per cup (190 mL) of oolong tea. The mean caffeine intake was 229 mg/d for men and 215 mg/d for women. Relative proportions of caffeine intake by beverage were 46% from green tea, 44% to 47% from coffee, 3% from black tea, and 4% to 5% from oolong tea. For reproducibility, the Spearman correlation coefficients between the 2 questionnaires, administered 1 year apart for 85 participants (8 men and 77 women), were 0.79 for green tea, 0.87 for coffee, 0.77 for black tea, and 0.56 for oolong tea (10). The validity of the data was confirmed for the 85 participants by comparing the data from the questionnaire with those from four 3-day dietary records collected approximately 3 to 4 months apart (10). The mean frequency of consumption of green tea was 25.4 cups per week according to the questionnaire and 30.1 cups per week according to four 1-week dietary records (Spearman correlation coefficient, 0.47). The respective mean frequencies were 8.0 cups and 7.1 cups per week with a correlation coefficient of 0.79 for coffee, 1.4 cups and 1.6 cups per week with a correlation coefficient of 0.70 for black tea, and 1.8 cups and 1.2 cups per week with a correlation coefficient of 0.55 for oolong tea. When we restricted the data to the 77 women, the results were essentially the same. Assessment of Diabetes Cases Participants who reported having diabetes newly diagnosed by physicians on the 5-year follow-up questionnaire were considered to have incident diabetes. To examine the validity of self-reporting of diabetes, we compared self-report data with laboratory findings and treatment status in a sample of 1230 men and 1837 women. We considered elevated glucose concentrations (fasting serum glucose concentration 7.8 mmol/L [140 mg/dL] or a randomly measured concentration of 11.1 mmol/L [200 mg/dL]) or treatment with oral hypoglycemic agents or insulin to indicate new cases of diabetes. Recent criteria from the American Diabetes Association (12) were not used because the cases in our study were diagnosed before 1995. The sensitivity of self-reporting was 70% for men and 75% for women; the specificity was 95% for men and 98% for women. Statistical Analysis To examine potential confounding variables reported from previous studies (3-7), we presented baseline characteristics according to the frequency of consumption for each beverage. Tests for trends were conducted by using the median values of confounding variables in each category of beverage; the linear regression model was used for continuous variables, and the logistic regression model was used for categorical variables. The odds ratios for incident type 2 diabetes were calculated in each category of beverage consumption and in each quartile of caffeine intake; less than 1 cup per week or the lowest quartile was used as the reference category. We estimated age, sex, and BMI-adjusted odds ratios and multivariable odds ratios using the logistic regression model, adjusting for age (in years), sex, sex-specific quintiles of BMI (weight in kilograms divided by the square of height in meters), parental history of diabetes (yes or no), smoking status (never, former, or current [1 to 19, 20 to 29, or 30 cigarettes/d]), alcohol intake (never, former, or current [1 to 22, 23 to 45, 46 to 68, or 69 g/d]), sex-specific quintiles of magnesium intake, hours of walking (<0.5, 0.5, 0.6 to 0.9, and 1.0 h/d), and hours of participation in sports (<1, 1 to 2, 3 to 4, and 5 h/wk). Sex-specific quintiles of BMI and magnesium intake were used because of different distributions between the sexes. We adjusted for magnesium intake because previous cohort studies indicated an inverse association between magnesium intake and risk for diabetes (13, 14). We conducted a test for trend by treating median values of each category of beverage or caffeine intake as continuous variables. We examined the association between caffeine intake and the risk for diabetes stratified by age group (40 to 54 years and 55 to 65 years), sex, family history of diabetes (yes or no), current smoking status (yes or no), current alcohol intake (yes or no), magnesium intake (below and above the sex-specific median), BMI (<25.0 kg/m2 and 25.0 kg/m2), hours of walking (<0.5 and 0.5 h/d), and hours of participation in sports (<5 and 5 h/wk). The interactions with these stratified variables were tested by using cross-product terms of caffeine intake and the stratified variables. All analyses were conducted by using the SAS statistical package, version 8.2 (SAS Institute Inc., Cary, North Carolina). P values for statistical tests were 2-tailed, and 95% CIs were estimated. Role of the


Public Health Nutrition | 2011

Comparison of relative validity of food group intakes estimated by comprehensive and brief-type self-administered diet history questionnaires against 16 d dietary records in Japanese adults.

Satomi Kobayashi; Kentaro Murakami; Satoshi Sasaki; Hitomi Okubo; Naoko Hirota; Akiko Notsu; Mitsuru Fukui; Chigusa Date

OBJECTIVE To compare the relative validity of food group intakes derived from a comprehensive self-administered diet history questionnaire (DHQ) and a brief-type DHQ (BDHQ) developed for the assessment of Japanese diets during the previous month using semi-weighed dietary records (DR) as a reference method. DESIGN Between November 2002 and September 2003, a 4 d DR (covering four non-consecutive days), a DHQ (150-item semi-quantitative questionnaire) and a BDHQ (fifty-eight-item fixed-portion-type questionnaire) were completed four times (once per season) at 3-month intervals. SETTING Three areas in Japan: Osaka, Nagano and Tottori. SUBJECTS Ninety-two Japanese women aged 31-69 years and ninety-two Japanese men aged 32-76 years. RESULTS Median food group intakes were estimated well for approximately half of the food groups. No statistically significant differences were noted between a 16 d DR and the first DHQ (DHQ1) or between the DR and the first BDHQ (BDHQ1) in fifteen (44 %) and fifteen (52 %) food items for women and in fourteen (41 %) and sixteen (55 %) food items for men, respectively, indicating that both questionnaires estimated median values reasonably well. Median Spearmans correlation coefficients with the DR were 0·43 (range: -0·09 to 0·77) for DHQ1 and 0·44 (range: 0·14 to 0·82) for BDHQ1 in women, with respective values of 0·44 (range: 0·08 to 0·87) and 0·48 (range: 0·22 to 0·83) in men, indicating reasonable ranking ability. Similar results were observed for mean values of the four DHQ and BDHQ. CONCLUSIONS In terms of food intake estimates, both the DHQ and the BDHQ showed reasonable validity.


Journal of Epidemiology | 2012

Both Comprehensive and Brief Self-Administered Diet History Questionnaires Satisfactorily Rank Nutrient Intakes in Japanese Adults

Satomi Kobayashi; Satoru Honda; Kentaro Murakami; Satoshi Sasaki; Hitomi Okubo; Naoko Hirota; Akiko Notsu; Mitsuru Fukui; Chigusa Date

Background A comprehensive self-administered diet history questionnaire (DHQ: 150-item semi-quantitative questionnaire) and a brief self-administered DHQ (BDHQ: 58-item fixed-portion–type questionnaire) were developed for assessing Japanese diets. We compared the relative validity of nutrient intake derived from DHQ with that from the BDHQ, using semi-weighed 16-day dietary records (DRs) as reference. Methods Ninety-two Japanese women aged 31 to 69 years and 92 Japanese men aged 32 to 76 years completed a 4-nonconsecutive-day DR, a DHQ, and a BDHQ 4 times each (once per season) in 3 areas of Japan (Osaka, Nagano, and Tottori). Results No significant differences were seen in estimates of energy-adjusted intakes of 42 selected nutrients (based on the residual method) between the 16-day DRs and the first DHQ (DHQ1) or between the DR and the first BDHQ (BDHQ1) for 18 (43%) and 14 (33%) nutrients, respectively, among women and for 4 (10%) and 21 (50%) nutrients among men. The median (interquartile range) Pearson correlation coefficients with the DR for energy-adjusted intakes of the 42 nutrients were 0.57 (0.50 to 0.64) for the DHQ1 and 0.54 (0.45 to 0.61) for the BDHQ1 in women; in men, the respective values were 0.50 (0.42 to 0.59) and 0.56 (0.41 to 0.63). Similar results were observed for the means of the 4 DHQs and BDHQs. Conclusions The DHQ and BDHQ had satisfactory ranking ability for the energy-adjusted intakes of many nutrients among the present Japanese population, although these instruments were satisfactory in estimating mean values for only a small number of nutrients.


Journal of the American College of Cardiology | 2008

Fish, ω-3 Polyunsaturated Fatty Acids, and Mortality From Cardiovascular Diseases in a Nationwide Community-Based Cohort of Japanese Men and Women: The JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study

Kazumasa Yamagishi; Hiroyasu Iso; Chigusa Date; Mitsuru Fukui; Kenji Wakai; Shogo Kikuchi; Yutaka Inaba; Naohito Tanabe; Akiko Tamakoshi

OBJECTIVES The objective of our study was to test the hypothesis that fish or omega-3 polyunsaturated fatty acids (PUFA) intakes would be inversely associated with risks of mortality from ischemic heart disease, cardiac arrest, heart failure, stroke, and total cardiovascular disease. BACKGROUND Data on associations of dietary intake of fish and of omega-3 PUFA with risk of cardiovascular disease among Asian societies have been limited. METHODS We conducted a prospective study consisting of 57,972 Japanese men and women. Dietary intakes of fish and omega-3 PUFA were determined by food frequency questionnaire, and participants were followed up for 12.7 years. Hazard ratios and 95% confidence intervals were calculated according to quintiles of fish or omega-3 PUFA intake. RESULTS We observed generally inverse associations of fish and omega-3 PUFA intakes with risks of mortality from heart failure (multivariable hazard ratio [95% confidence interval] for highest versus lowest quintiles = 0.76 [0.53 to 1.09] for fish and 0.58 [0.36 to 0.93] for omega-3 PUFA). Associations with ischemic heart disease or myocardial infarction were relatively weak and not statistically significant after adjustment for potential risk factors. Neither fish nor omega-3 PUFA dietary intake was associated with mortality from total stroke, its subtypes, or cardiac arrest. For mortality from total cardiovascular disease, intakes of fish and omega-3 PUFA were associated with 18% to 19% lower risk. CONCLUSIONS We found an inverse association between fish and omega-3 PUFA dietary intakes and cardiovascular mortality, especially for heart failure, suggesting a protective effect of fish intake on cardiovascular diseases.


Journal of the American College of Cardiology | 2008

Clinical ResearchDiet and Cardiovascular DiseaseFish, ω-3 Polyunsaturated Fatty Acids, and Mortality From Cardiovascular Diseases in a Nationwide Community-Based Cohort of Japanese Men and Women: The JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study

Kazumasa Yamagishi; Hiroyasu Iso; Chigusa Date; Mitsuru Fukui; Kenji Wakai; Shogo Kikuchi; Yutaka Inaba; Naohito Tanabe; Akiko Tamakoshi

OBJECTIVES The objective of our study was to test the hypothesis that fish or omega-3 polyunsaturated fatty acids (PUFA) intakes would be inversely associated with risks of mortality from ischemic heart disease, cardiac arrest, heart failure, stroke, and total cardiovascular disease. BACKGROUND Data on associations of dietary intake of fish and of omega-3 PUFA with risk of cardiovascular disease among Asian societies have been limited. METHODS We conducted a prospective study consisting of 57,972 Japanese men and women. Dietary intakes of fish and omega-3 PUFA were determined by food frequency questionnaire, and participants were followed up for 12.7 years. Hazard ratios and 95% confidence intervals were calculated according to quintiles of fish or omega-3 PUFA intake. RESULTS We observed generally inverse associations of fish and omega-3 PUFA intakes with risks of mortality from heart failure (multivariable hazard ratio [95% confidence interval] for highest versus lowest quintiles = 0.76 [0.53 to 1.09] for fish and 0.58 [0.36 to 0.93] for omega-3 PUFA). Associations with ischemic heart disease or myocardial infarction were relatively weak and not statistically significant after adjustment for potential risk factors. Neither fish nor omega-3 PUFA dietary intake was associated with mortality from total stroke, its subtypes, or cardiac arrest. For mortality from total cardiovascular disease, intakes of fish and omega-3 PUFA were associated with 18% to 19% lower risk. CONCLUSIONS We found an inverse association between fish and omega-3 PUFA dietary intakes and cardiovascular mortality, especially for heart failure, suggesting a protective effect of fish intake on cardiovascular diseases.


Cancer Science | 2005

Dietary intakes of fat and fatty acids and risk of breast cancer: a prospective study in Japan.

Kenji Wakai; Koji Tamakoshi; Chigusa Date; Mitsuru Fukui; Sadao Suzuki; Yingsong Lin; Yoshimitsu Niwa; Kazuko Nishio; Hiroshi Yatsuya; Takaaki Kondo; Shinkan Tokudome; Akio Yamamoto; Hideaki Toyoshima; Akiko Tamakoshi

To examine the possible association of dietary fat and fatty acids with breast cancer risk in a population with a low total fat intake and a high consumption of fish, we analyzed data from the Japan Collaborative Cohort (JACC) Study. From 1988 to 1990, 26 291 women aged 40–79 years completed a questionnaire on dietary and other factors. Intakes of fat or fatty acids were estimated by using a food frequency questionnaire. Rate ratios (RR) were computed by fitting proportional hazards models. During the mean follow‐up of 7.6 years, 129 breast cancer cases were documented. We found no clear association of total fat intake with breast cancer risk; the multivariate‐adjusted RR across quartiles were 1.00, 1.29, 0.95, and 0.80 (95% confidence interval [CI] 0.46–1.38). A significant decrease in the risk was detected for the highest quartile of intake compared with the lowest for fish fat and long‐chain n‐3 fatty acids; the RR were 0.56 (95% CI 0.33–0.94) and 0.50 (0.30–0.85), respectively. A decreasing trend in risk was also suggested with an increasing intake of saturated fatty acids (trend P = 0.066). Among postmenopausal women at baseline, the highest quartile of vegetable fat intake was associated with a 2.08‐fold increase in risk (95% CI 1.05–4.13). This prospective study did not support any increase in the risk of breast cancer associated with total or saturated fat intake, but it suggested the protective effects of the long‐chain n‐3 fatty acids that are abundant in fish. (Cancer Sci 2005; 96: 590 – 599)


British Journal of Nutrition | 2008

Reproducibility and relative validity of dietary glycaemic index and load assessed with a self-administered diet-history questionnaire in Japanese adults

Kentaro Murakami; Satoshi Sasaki; Yoshiko Takahashi; Hitomi Okubo; Naoko Hirota; Akiko Notsu; Mitsuru Fukui; Chigusa Date

Although many epidemiological studies have examined the association of dietary glycaemic index (GI) and glycaemic load (GL) with health outcomes, information on the reproducibility and relative validity of these variables estimated from dietary questionnaires is extremely limited. We examined the reproducibility and relative validity of dietary GI and GL assessed with a self-administered diet-history questionnaire (DHQ) in adult Japanese. A total of ninety-two Japanese women and ninety-two Japanese men aged 31-76 years completed the DHQ (assessing diet during the preceding month) and 4 d dietary records (DR) in each season over a 1-year period (DHQ1-4 and DR1-4, respectively) and the DHQ at 1 year after completing DHQ1 (DHQ5). We used intraclass correlations between DHQ1 and DHQ5 to assess reproducibility, and Pearson correlations between the mean of DR1-4 and mean of DHQ1-4 and between the mean of DR1-4 and DHQ1 to assess relative validity. Reproducibility correlations for dietary GI and GL were 0.57 and 0.69 among women and 0.65 and 0.58 among men, respectively. Validity correlations for dietary GI and GL assessed by DHQ1-4 were 0.72 and 0.66 among women and 0.65 and 0.71 among men, respectively. Corresponding correlations for DHQ1 were 0.53 and 0.58 among women and 0.57 and 0.60 among men, respectively. White rice was the major contributor to GI and GL in both methods (49-64 %). These data indicate reasonable reproducibility and relative validity of dietary GI and GL assessed by a DHQ for Japanese adults, whose dietary GI and GL are primarily determined by the GI of white rice.


Journal of Orthopaedic Science | 2009

JOA Back Pain Evaluation Questionnaire (JOABPEQ)/JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) The report on the development of revised versions April 16, 2007

Mitsuru Fukui; Kazuhiro Chiba; Mamoru Kawakami; Shinichi Kikuchi; Shin-ichi Konno; Masabumi Miyamoto; Atsushi Seichi; Tadashi Shimamura; Osamu Shirado; Toshihiko Taguchi; Kazuhisa Takahashi; Katsushi Takeshita; Toshikazu Tani; Yoshiaki Toyama; Kazuo Yonenobu; Eiji Wada; Takashi Tanaka; Yoshio Hirota

1 Laboratory of Statistics, Osaka City University Faculty of Medicine, Osaka, Japan 2 Department of Orthopaedic Surgery, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan 3 Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, Japan 4 Department of Orthopaedic Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan 5 Department of Orthopedic Surgery, Nippon Medical School, Tokyo, Japan 6 Department of Orthopaedic Surgery, The University of Tokyo, Tokyo, Japan 7 Department of Orthopaedic Surgery, Iwate Medical University School of Medicine, Morioka, Japan 8 Department of Orthopaedic Surgery, Saitama Medical School. Saitama, Japan 9 Department of Orthopedic Surgery, Yamaguchi University School of Medicine, Yamaguchi, Japan 10 Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan 11 Department of Orthopaedics, Kochi Medical School, Kochi, Japan 12 Department of Orthopaedic Surgery, Hoshigaoka Koseinenkin Hospital, Osaka, Japan 13 National Hospital Organization, Osaka-Minami Medical Center, Osaka, Japan 14 Department of Internal Medicine, Houai Hospital, Osaka, Japan 15 Department of Public Health, Osaka City University Faculty of Medicine, Osaka, Japan


Cancer Epidemiology, Biomarkers & Prevention | 2007

Dietary Fiber and Risk of Colorectal Cancer in the Japan Collaborative Cohort Study

Kenji Wakai; Chigusa Date; Mitsuru Fukui; Koji Tamakoshi; Yoshiyuki Watanabe; Norihiko Hayakawa; Masayo Kojima; Miyuki Kawado; Koji Suzuki; Shuji Hashimoto; Shinkan Tokudome; Kotaro Ozasa; Sadao Suzuki; Hideaki Toyoshima; Yoshinori Ito; Akiko Tamakoshi

To examine the association of dietary fiber with the risk of colorectal cancer in a population with a high incidence of cancer and a low fiber intake, we analyzed the data from the Japan Collaborative Cohort Study. From 1988 to 1990, 43,115 men and women aged 40 to 79 years completed a questionnaire on dietary and other factors. Intake of dietary fiber was estimated using a food frequency questionnaire. Rate ratios (RR) were computed by fitting proportional hazards models. During the mean follow-up of 7.6 years, 443 colorectal cancer cases were recorded. In all participants, we found a decreasing trend in risk of colorectal cancer with increasing intake of total dietary fiber; the multivariate-adjusted RRs across quartiles were 1.00, 0.96 [95% confidence interval (95% CI), 0.72-1.27], 0.72 (0.53-0.99), and 0.73 (0.51-1.03; Ptrend = 0.028). This trend was exclusively detected for colon cancer: the corresponding RRs were 1.00, 0.90 (95% CI, 0.64-1.26), 0.56 (0.38-0.83), and 0.58 (0.38-0.88; Ptrend = 0.002). The decrease in RRs with increasing intake of dietary fiber was larger in men than in women. No material differences appeared in the strength of associations with the risk between water-soluble and insoluble dietary fiber. For food sources of fiber, bean fiber intake was somewhat inversely correlated with colorectal cancer risk. This prospective study supported potential protective effects of dietary fiber against colorectal cancer, mainly against colon cancer. The role of dietary fiber in the prevention of colorectal cancer seems to remain inconsistent, and further investigations in various populations are warranted. (Cancer Epidemiol Biomarkers Prev 2007;16(4):668–75)


Molecular Genetics and Metabolism | 2011

Experimental evidence that phenylalanine is strongly associated to oxidative stress in adolescents and adults with phenylketonuria

Yoshitami Sanayama; Hironori Nagasaka; Masaki Takayanagi; Toshihiro Ohura; Osamu Sakamoto; Tetsuya Ito; Mika Ishige-Wada; Hiromi Usui; Makoto Yoshino; Akira Ohtake; Tohru Yorifuji; Hirokazu Tsukahara; Satoshi Hirayama; Takashi Miida; Mitsuru Fukui; Yoshiyuki Okano

Few studies have looked at optimal or acceptable serum phenylalanine levels in later life in patients with phenylketonuria (PKU). This study examined the oxidative stress status of adolescents and adults with PKU. Forty PKU patients aged over fifteen years were enrolled, and were compared with thirty age-matched controls. Oxidative stress markers, anti-oxidant enzyme activities in erythrocytes, and blood anti-oxidant levels were examined. Nitric oxide (NO) production was also examined as a measure of oxidative stress. Plasma thiobarbituric acid reactive species and serum malondialdehyde-modified LDL levels were significantly higher in PKU patients than control subjects, and correlated significantly with serum phenylalanine level (P<0.01). Plasma total anti-oxidant reactivity levels were significantly lower in the patient group, and correlated negatively with phenylalanine level (P<0.001). Erythrocyte superoxide dismutase and catalase activities were higher and correlated significantly with phenylalanine level (P<0.01). Glutathione peroxidase activity was lower and correlated negatively with phenylalanine level (P<0.001). The oxidative stress score calculated from these six parameters was significantly higher in patients with serum phenylalanine of 700-800 μmol/l. Plasma anti-oxidant substances, beta-carotene, and coenzyme Q(10) were also lower (P<0.001), although the decreases did not correlate significantly with the phenylalanine level. Serum nitrite/nitrate levels, as stable NO products, were higher together with low serum asymmetric dimethylarginine, as an endogenous NO inhibitor. Oxidative stress status is closely linked with serum phenylalanine levels. Phenylalanine level in should be maintained PKU below 700-800 μmol/l even in adult patients.

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Mamoru Kawakami

Wakayama Medical University

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Kazuhiro Chiba

Tokyo University of Agriculture and Technology

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