Dietary melatonin and liver cancer incidence in Japan: From the Takayama study.

There is some biological plausibility that exogenous melatonin plays a role in preventing liver carcinogenesis. There has been little research on the association between melatonin intake in a normal diet and health outcomes. We evaluated the association between dietary melatonin intake and the incidence of liver cancer in a population-based prospective study in Japan. This study included 30,824 residents of Takayama city who were 35 years of age or older in 1992 and had participated in the Takayama study, Japan. Dietary intake was assessed using a validated food frequency questionnaire at the baseline. Melatonin content in foods was measured by liquid chromatography-tandem mass spectrometry. Cancer incidence was confirmed through regional population-based cancer registries in Gifu. Liver cancer was defined as code C22 according to the International Classification of Diseases and Related Health Problems, 10th Revision. Hazard ratios for liver cancer were estimated for the tertile groups of melatonin intake using a Cox proportional hazards model. During the mean follow-up period of 13.6 years, 189 individuals developed liver cancer. Compared with subjects in the lowest tertile of melatonin intake, those in the middle and highest tertiles had decreased risks of liver cancer, with a significant linear trend after multivariate adjustments (hazard ratios: 0.64 and 0.65, respectively, trend p = 0.023). There was no significant interaction by sex (interaction p = 0.54). This initial finding, which needs to be confirmed by further studies, suggests that consuming melatonin-containing foods might play a role in the prevention of liver cancer.

Dietary polyamine intake and all-cause and cause-specific mortality in Japanese adults in the Takayama study.

Epidemiological studies on the potential health effects of dietary polyamines are scarce. The present study aimed to estimate habitual intake of polyamines (putrescine, spermidine and spermine) and examine whether spermidine intake is inversely associated with all-cause and cause-specific mortality in a population-based cohort study in Japan. The study included 13 355 men and 15 724 women aged 35 years and older. Diet was assessed via a validated FFQ at the baseline in 1992. The intake of polyamines was estimated mainly using databases of polyamine content in foods consumed among Japanese population. Sex-specific hazard ratios (HR) and 95 % CI for all-cause and cause-specific mortality were estimated according to polyamine quartiles. During 16 years of follow-up, 2901 deaths in men and 2438 in women occurred. The intake of any polyamine was not significantly associated with all-cause or cause-specific mortality after controlling for covariates in men and women. There was a suggestive positive association between spermidine intake and cancer mortality in women: HR for the highest v. lowest quartile were 1·38 (95 % CI (0·99, 1·93); Ptrend = 0·02). Our results did not provide support for the notion that dietary spermidine has beneficial effects on mortality. Further studies on dietary polyamines and longevity, as well as the morbidity of specific diseases, including cancer, are needed across populations with different dietary habits.

Personal characteristics associated with handwashing behaviour among Japanese university students studying abroad: Prospective observational studies.

BACKGROUND: Hand hygiene is recommended to travellers to prevent common travel-related illnesses such as diarrhoea and respiratory infection. For effective hygiene promotion interventions, we aimed to identify the personal characteristics associated with handwashing behaviour. METHODS: Prospective observational studies consisting of pre- and post-travel surveys were conducted among Japanese university students studying abroad between 2016 and 2018 (n = 825; 6-38 travel days). Associations of age, sex, study major, and overseas travel experience with handwashing behaviour (5-point scale) were evaluated using ordinal logistic regression models, with adjustment for destination, travel duration, and psychological factors (risk perception of diarrhoea and concern about hygiene). RESULTS: Among the participants in our analysis (n = 629), 28.0 % washed their hands before every meal while abroad. The male sex and no overseas travel experience were associated with decreased frequency of infrequent handwashing, even after adjusting for all potential confounding factors, whereas the study major was not associated. The adjusted odds ratios (95 % confidence intervals) were 0.74 (0.56-0.99) for men vs. women and 0.69 (0.52-0.93) for no overseas travel experience vs. overseas travel experience but not to the current destination. CONCLUSIONS: The lack of overseas travel experience correlated with handwashing frequency in both men and women. In addition to the travel destination, the male sex and no overseas travel experience should be highlighted in pretravel hand hygiene interventions.

Associations of the timing of sleep and meals with the presence of gastroesophageal reflux disease in community-dwelling women in Japan.

BACKGROUND: It has been suspected that circadian rhythms may play a part in the pathogenesis of gastrointestinal diseases including gastroesophageal reflux disease (GERD). The present study aimed to examine the cross-sectional association of the timing of sleep and meals with the presence of GERD in community-dwelling women in Japan. METHODS: In total, 605 women responded to a self-administered questionnaire asking for information on GERD symptoms, sleep habits, sleep disturbances and the timing of meals. GERD symptoms were evaluated using the Frequency Scale for the Symptoms of GERD, and participants with a score of more than seven points were classified as having GERD. RESULTS: In total, 104 (17.2%) women were found to have GERD. Later bedtime on both weekdays and weekends and later midpoint of sleep were significantly associated with the odds ratios (OR) of GERD after controlling for covariates: ORs for each 1 h delay were 1.31 (95% confidence interval [CI] = 1.03-1.68), 1.38 (95% CI = 1.08-1.75) and 1.43 (95% CI = 1.06-1.95). Having lunch at irregular times was significantly associated with the increased OR of GERD (1.99; 95% CI = 1.02-3.91). Longer overnight fasting duration and longer time intervals from the midpoint of sleep to breakfast and lunch were significantly associated with decreased OR of GERD (ORs for each 1 h increase were 0.73 [95% CI = 0.56-0.95], 0.64 [95% CI = 0.46-0.88] and 0.70 [95% CI = 0.51-0.96]). CONCLUSIONS: These data suggest that the timing of sleep and timing of meals relative to the sleep/wake cycle are associated with the presence of GERD.

Milk and dairy product intakes, intestinal bacteria, and respiratory infections in children of elementary school age and older in Japan.

OBJECTIVES: The aim of this study was to examine the associations between milk and dairy product intakes, intestinal bacteria, and respiratory infections in children of elementary school age and older in Japan. METHODS: We conducted cross-sectional surveys each year from 2013 to 2015 for grades 2, 5, and 8 students of an elementary and junior high school (n = 1020). Exclusion owing to ineligibility regarding data on dietary intake, respiratory infections, and intestinal bacteria led to 922 participants for the analyses. Dietary intake was assessed with a self-administered food frequency questionnaire. Respiratory infections occurring ≥ 4 episodes over the past year were determined based on the caregivers' reports. Intestinal bacteria (species and counts) were analyzed with real-time polymerase chain reaction. Logistic regression models were used to estimate the odds ratios (ORs) and 95% CIs. RESULTS: The odds of ≥ 4 respiratory infection episodes decreased with higher milk intake after adjusting for potential confounders, and the ORs (95% CIs) for the second and third tertile categories, compared with the first tertile category, were 0.91 (0.58-1.42) and 0.48 (0.29-0.77), respectively (P for trend = 0.001). A decreasing trend in the ORs for lactic acid drink intake was observed only in those with a low count of intestinal Faecalibacterium prausnitzii. CONCLUSIONS: We found that higher milk intake was inversely associated with respiratory infections in children older than preschool age. Higher lactic acid drink intake could be inversely associated only in children with a low F. prausnitzii count in the intestine.

Association of dietary fibre intake with subsequent fasting glucose levels and indicators of adiposity in school-age Japanese children.

OBJECTIVE: To evaluate the relationships of fibre intake with subsequent BMI sd-score, waist-to-height ratio and serum fasting glucose levels among school-age Japanese children. DESIGN: This is a prospective study of school-age Japanese children. Participants were followed from 6-7 to 9-10 years of age (follow-up rate: 92·0 %). Fibre intake was assessed using a validated FFQ. Serum fasting glucose was measured by a hexokinase enzymatic method. Using a general linear model, the associations between dietary fibre intake at baseline and BMI sd-score, waist-to-height ratio, and serum levels of fasting glucose at follow-up were evaluated after considering potential confounding factors. SETTING: Public elementary schools in a city in Japan. PARTICIPANTS: A total of 2784 students. RESULTS: The estimated means for fasting glucose at 9-10 years of age were 86·45, 85·68, 85·88 and 85·58 mg/dl in the lowest, second, third and highest quartile of fibre intake at 6-7 years of age, respectively (P = 0·033, trend P = 0·018). Higher fibre intake at 6-7 years of age was associated with lower waist-to-height ratio at 9-10 years of age (trend P = 0·023). The change in fibre intake was inversely associated with concurrent change of BMI sd-score (trend P = 0·044). CONCLUSION: These results suggest that dietary fibre intake may be potentially effective to limit excess weight gain and lower glucose levels during childhood.

Associations of Plasma 25-Hydroxy Vitamin D and Dietary Vitamin D Intake with Insulin Resistance in Healthy Japanese Women.

We investigated the associations of plasma 25-hydroxy vitamin D (25(OH)D) concentration and the dietary intake of vitamin D with insulin resistance in Japanese women. Study participants were 406 Japanese women attended a health examination. They were not taking hormones or medications for diabetes and had no history of cancer, ischemic heart disease, or stroke. Information regarding medical history and lifestyle factors was obtained by a self-administered questionnaire, while hours of sun exposure were determined through interviews. Dietary intake of vitamin D was evaluated using a validated food frequency questionnaire. Fasting plasma glucose and insulin concentrations were measured, and insulin resistance (HOMA-IR) scores were calculated based on homeostasis model assessment. Women with vitamin D deficiency (25(OH)D<20 ng/mL) had significantly higher fasting plasma insulin concentration and HOMA-IR than did the other women. Plasma 25(OH)D concentration was significantly and inversely associated with fasting plasma insulin level and HOMA-IR after controlling for age, season, menopausal status, BMI, smoking status, alcohol intake, physical exercise, and intakes of fat and calcium. Dietary vitamin D intake was not associated with HOMA-IR concentration after adjusting for these covariates and hours of sun exposure. Although significant inverse association between plasma 25(OH)D concentration and HOMA-IR was observed in women with a low BMI, low fat intake, or a high calcium intake, the interaction terms were not statistically significant. Data suggest that plasma vitamin D, but not dietary vitamin D, is inversely associated with fasting plasma insulin concentration and HOMA-IR in non-diabetic Japanese women.

Diarrhea and related personal characteristics among Japanese university students studying abroad in intermediate- and low-risk countries.

Despite an increasing number of students studying abroad worldwide, evidence about health risks while they are abroad is limited. Diarrhea is considered the most common travelers' illness, which would also apply to students studying abroad. We examined diarrhea and related personal characteristics among Japanese students studying abroad. Japanese university students who participated in short-term study abroad programs between summer 2016 and spring 2018 were targeted (n = 825, 6-38 travel days). Based on a 2-week-risk of diarrhea (passing three or more loose or liquid stools per day) among travelers by country, the destination was separated into intermediate- and low-risk countries. After this stratification, the associations between personal characteristics and diarrhea during the first two weeks of their stay were evaluated using logistic regression models. Among participants in intermediate-risk countries, teenagers, males and those with overseas travel experience were associated with an elevated risk of diarrhea; the odds ratios (95% confidence intervals) were 2.42 (1.08-5.43) for teenagers (vs. twenties), 1.93 (1.08-3.45) for males (vs. females) and 2.37 (1.29-4.33) for those with overseas experience (vs. none). Even restricting an outcome to diarrhea during the first week did not change the results substantially. The same tendency was not observed for those in the low-risk countries. Teenage students, males and those with overseas travel experience should be cautious about diarrhea while studying abroad, specifically in intermediate-risk countries.

Sleep duration and the onset of menopause in Japanese women.

OBJECTIVE: Sleep characteristics may potentially affect the hormonal environment related to follicular degeneration. The present study aimed to examine the association between sleep duration and the onset of menopause in Japanese women. METHODS: We conducted a prospective study among 3,090 premenopausal Japanese women aged 35 to 56 years derived from participants in the Takayama Study. Habitual sleep duration was determined by a self-administered questionnaire at the baseline. Menopausal status was defined as the absence of menstruation for 12 months or more. The Cox proportional hazard model was used to estimate the hazard ratio of the occurrence of menopause for each category of sleep duration (≤6, 8, and ≥9 h) as compared with 7 hours of sleep after controlling for age, parity, body mass index, smoking status, years of education, and lifelong irregular menstrual cycle. RESULTS: During the 10 follow-up years, 1,776 women experienced natural menopause. Sleep duration of ≤6 hours was significantly associated with decreased hazard ratio of menopause (0.88; 95% confidence interval, 0.78-0.99). CONCLUSIONS: The data suggest that short sleep duration is associated with later onset of menopause.

Sleep-related factors and circulating levels of sex hormones in premenopausal Japanese women.

Sleep disruption and circadian disruption have been proposed to be risk factors of breast cancer. The present study examined the associations of sleep-related factors, referring to night shift work, sleep habits, and sleep disturbances, with the plasma levels of sex hormones in premenopausal Japanese women. Study participants were 432 women who had regular menstrual cycles less than 40 days long. Information on their history of night shift work and sleep disturbances was obtained using a self-administered questionnaire. Information on their sleep habits, such as usual wake-up times, bedtimes, and ambient light level while sleeping, was obtained in an interview. The participants' height and weight were measured. Plasma concentrations of estradiol, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), FSH, and LH were also measured. After controlling for the phase of the menstrual cycle and other covariates, more years of night shift work ≥ once a week during the past 10 years was significantly associated with a lower SHBG and a higher free estradiol level. Shorter sleep duration was significantly associated with the higher total, bioavailable, and free testosterone levels. Sleep disturbance by awaking after sleep onset was significantly associated with a high free estradiol level. The data suggest that long-term night shift work, short sleep duration, and arousal during sleep are associated with higher estradiol or testosterone levels in premenopausal women.

Validity of self-reported skin color by using skin color evaluation scale.

INTRODUCTION: Although skin color has been suggested to be associated with the risk of some chronic disease, there has been no validated visual skin-color scale, with which subjects can self-report their skin color. Our objective was to develop a visual skin color evaluation scale for self-reporting that would be useful in large-scale epidemiological studies. MATERIALS AND METHODS: Study participants were 99 university Japanese students aged 19-29. We developed a skin color evaluation scale consisting of six colors from light to dark. Participants were asked to choose one color that was the closest to their skin color. Their skin color was measured on the back of the hand and the inner upper arm by an examiner using a narrowband reflective spectrophotometer. Self-reported skin color was compared with the melanin and erythema indices. RESULTS: Spearman's rank correlation coefficients of self-reported color with the melanin index after adjusted for age, temperature, and humidity were moderate but significant at both sites for both men and women. The correlation coefficients with the erythema index were significant only on the back of the hand for men. The higher melanin index was significantly associated with the darker skin color in both sexes for both sites. The erythema index showed such a significant trend only in men and not in women. CONCLUSIONS: The validity of the skin color chart was moderate of melanin among Japanese people. It may be useful for large population studies examining the relationships between skin color and health outcomes.

Dietary lactose and galactose intakes are associated with a later onset of natural menopause among women in a Japanese community.

Galactose and its metabolites, primarily derived from lactose, may have toxic effects on the ovary. We aimed to prospectively examine the associations of galactose and lactose intakes with the onset of natural menopause. The data of a population-based cohort study in a Japanese community (the Takayama study) initiated in 1992 were analysed, with follow-up data collected in 2002. Among the participants of the Takayama study, premenopausal women (n 3115) aged 35-56 years at baseline were included in this study. Dietary intake, including lactose and galactose was assessed only at baseline using a FFQ. The menopausal status and age at menopause were determined based on the participants' self-reports, and natural menopause was defined as the absence of menstruation for 12 months or more. Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95 % CI. A total of 1790 women experienced natural menopause within the 10-year follow-up. Lactose and galactose intakes were associated with a later onset of natural menopause after adjusting for potential confounding factors and the HR (95 % CI) for the highest v. lowest quartile were 0·80 (0·69, 0·92) (P-trend = 0·001) in lactose and 0·86 (0·74, 1·00) in galactose (P-trend = 0·036), respectively. High intakes of lactose and galactose were associated with a later onset of natural menopause. Despite the presumed ovotoxicity effects, lactose and galactose intakes at usual levels may not be deleterious to the ovarian aging process among Japanese community-dwelling women.

Phase II Study of a Multi-center Randomized Controlled Trial to Evaluate Oral Vitamin B12 Treatment for Vitamin B12 Deficiency After Total Gastrectomy in Gastric Cancer Patients.

BACKGROUND/AIM: This prospective multi-central randomized phase II trial evaluated the efficacy and safety of oral Vitamin B12 500 µg/day replacement compared with oral Vitamin B12 1,500 µg/day in patients with Vitamin B12 deficiency after total gastrectomy for gastric cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive oral Vitamin B12 500 µg/day or Vitamin B12 1,500 µg/day in a 1:1 ratio with a minimization method. The primary endpoint was the incidence of a normal serum Vitamin B12 level at three months after treatment. RESULTS: From January 2018 to December 2021, 3 institutions collaborated with the present study, and 74 patients were registered from these 3 institutions. The study was prematurely closed due to poor accrual after reaching almost 50% of its goal. Among the 74 recruited patients, 36 were allocated to the Vitamin B12 500 µg/day arm and 38 to Vitamin B12 1,500 µg/day arm. The incidences of patients with a normal Vitamin B12 level at 3 months (serum Vitamin B12 level >200 pg/ml) were 91.7% (33/36) in the Vitamin B12 500 µg/day arm and 100% (38/38) in the Vitamin B12 1,500 µg/day arm (p=0.3587). The types of clinical symptoms with Vitamin B12 deficiency that improved with Vitamin B12 treatment and the degree of improvement were also similar. CONCLUSION: Although the primary endpoint of the present study was not met, it was found that oral Vitamin B12 500 µg/day replacement is as effective and safe as oral Vitamin B12 1,500 µg/day replacement for Vitamin B12 deficiency.

Dietary advanced glycation end products and cancer risk in Japan: From the Takayama study.

Few large epidemiological studies have evaluated the association between dietary advanced glycation end products (AGEs) and cancer risk. We evaluated the relationship between dietary AGE intake and the incidence of total cancer and site-specific cancers in a population-based prospective study in Japan. Participants were 14,173 men and 16,549 women who were 35 years of age or older in 1992. Dietary intake was assessed via a validated food frequency questionnaire. Intake of the AGE Nε -carboxymethyl-lysine (CML) was estimated using databases of CML content in foods determined using ultraperformance liquid chromatography-tandem mass spectrometry. Cancer incidence was confirmed through regional population-based cancer registries. During a mean follow-up period of 13.3 years, 1954 men and 1477 women developed cancer. We did not observe a significant association between CML intake and the risk of total cancer in men or women. In men, compared with the lowest quartile of CML intake, the hazard ratios of liver cancer for the second, third, and highest quartiles were 1.69 (95% CI: 0.92-3.10), 1.48 (95% CI: 0.77-2.84), and 2.10 (95% CI: 1.10-3.98; trend p = 0.04). Conversely, a decreased relative risk of male stomach cancer was observed for the second and highest quartiles of CML intake versus the lowest quartile, with hazard ratios of 0.73 and 0.67, respectively (trend p = 0.08). Our finding on the potential harmfulness of consuming AGEs on liver cancer risk is intriguing and warrants further study.

Associations of total nut and peanut intakes with all-cause and cause-specific mortality in a Japanese community: the Takayama study.

Numerous epidemiological studies have suggested that nut intake is associated with a reduced risk of mortality. Although diets and lifestyles differ by regions or races/ethnicities, few studies have investigated the associations among non-white, non-Western populations. We evaluated the associations of total nut and peanut intakes with all-cause and cause-specific mortality in a population-based prospective cohort in Japan. Participants (age: ≥35 years at baseline in 1992; n 31 552) were followed up until death or the end of follow-up in 2008. Those with cancer, CHD or stroke at baseline were excluded. Dietary intake was assessed only at baseline by using a validated FFQ. In total, 2901 men died during 183 299 person-years and 2438 women died during 227 054 person-years. The mean intakes of total nuts were 1·8 and 1·4 g/d in men and women, respectively. Although peanut intake accounted for approximately 80 % of the total nut intake, total nut and peanut intakes were inversely associated with all-cause mortality in men after adjusting for all potential confounders. For example, compared with the lowest quartile category, the adjusted hazard ratio (95 % CI) of total nut intake for all-cause mortality in men of the highest quartile category was 0·85 (95 % CI 0·75, 0·96) (Pfor trend = 0·034). Peanut intake was inversely associated with digestive disease mortality in men and CVD mortality in women. Total nut and peanut intakes, even in low amounts, were associated with a reduced risk of mortality particularly in men.

Associations Between Dietary Melatonin Intake and Total and Cause-Specific Mortality Among Japanese Adults in the Takayama Study.

Potential health benefits of melatonin have been suggested. Although melatonin is present in various foods, little is known about the health effects of dietary melatonin intake. We estimated habitual dietary melatonin intake and examined its association with total and cause-specific mortality in a population-based cohort study in Japan. Study subjects included 13,355 men and 15,724 women aged ≥35 years who responded to a self-administered questionnaire in 1992. Their diets were assessed via a food frequency questionnaire at baseline. The melatonin content in various foods on the questionnaire was measured to estimate melatonin intake. Mortality was ascertained during 16 years of follow-up (1992-2008). Hazard ratios (HRs) and 95% confidence intervals (CIs) for total and cause-specific mortality were calculated according to melatonin quartiles. A total of 5,339 deaths occurred during follow-up. Melatonin intake was significantly associated with decreased risks of total mortality, cardiovascular mortality, and noncancer, noncardiovascular mortality after controlling for covariates; HRs for the highest quartile of melatonin intake versus the lowest were 0.90 (95% CI: 0.82, 0.98; P for trend = 0.05), 0.85 (95% CI: 0.72, 0.99; P for trend = 0.10), and 0.77 (95% CI: 0.67, 0.90; P for trend = 0.003), respectively. The data suggest a potential benefit of dietary melatonin with regard to mortality rates.

Birth month and mortality in Japan: a population-based prospective cohort study.

Epidemiologic studies investigating the association between birth season and risk of mortality in adulthood are limited and have yielded inconclusive results. We aimed to examine the relationship between birth month and all-cause and cause-specific mortality, after controlling for potential confounders, including lifestyle and medical factors, in a population-based cohort study in Japan. We included 28,884 subjects (13,262 men and 15,622 women) from Takayama City, aged 35 years or older without cancer, stroke, and ischemic heart disease, who were born in Japan at baseline. Participants who were enrolled in 1992 were followed up for over 16 years. Information including place of birth, lifestyles, and medical history was obtained from a baseline questionnaire. We performed a Cox proportional hazards analysis to determine the association between birth month and all-cause and cause-specific mortality after adjusting for potential confounders. During the follow-up period (mean follow-up: 14.1 years), 5,303 deaths (2,881 men and 2,422 women) were identified. After controlling for multiple covariates, it was found that being born in April or June was associated with an increased risk of all-cause mortality compared to being born in January (hazard ratio [HR] 1.138; 95% confidence interval [CI], 1.006-1.288 and HR 1.169; 95% CI, 1.028-1.329, respectively). The HRs for cardiovascular mortality were significantly higher in participants born in March and May (HR 1.285; 95% CI, 1.056-1.565 and HR 1.293; 95% CI, 1.040-1.608, respectively). Our findings indicate that an individual's birth month may be an indicator of the susceptibility to mortality in later life.

Association Between Anger and Mortality in Women and Men: A Prospective Cohort Study in a Japanese Community.

Background: Anger is a common problem in society, and anger's relationship with mortality, in particular with cardiovascular mortality, has been studied mainly in male western population. There are no prospective studies in Japan, about the association between anger and mortality. Materials and Methods: This study examined the association of anger with all-cause and cause-specific mortality in a Japanese community. Data came from the Takayama Study, which recruited residents aged ≥35 years in 1992 from Takayama City in Gifu, Japan. The current study used information on anger that was obtained from the second survey in 2002. A total of 11,902 healthy participants aged ≥45 years completed a self-administered questionnaire. Anger was assessed using the Spielberger Trait Anger Scale. Results: The main causes of deaths during the follow-up period from 2002 to 2013 were 460 for neoplasm, 254 for cardiovascular, and 435 for other causes. After adjusting for potential confounders, we found a significant positive association between the trait anger score and the risk of cardiovascular mortality for women, with a hazard ratio for high versus low score of trait anger of 1.81 (95% confidence interval 0.91-3.63, p for trend = 0.04), but not for men. Conclusions: Data suggest that for Japanese women, high trait anger score may be associated with an increased risk of cardiovascular mortality. Potential gender differences in the association between trait anger and mortality should be further studied from the cultural context.

Dietary Intake of Nε-carboxymethyl-lysine, a Major Advanced Glycation End Product, is Not Associated with Increased Risk of Mortality in Japanese Adults in the Takayama Study.

BACKGROUND: Although endogenous advanced glycation end products (AGEs) have been implicated in the development of various chronic diseases, whether AGEs in foods represent a risk to human health remains unknown. OBJECTIVES: We aimed to estimate the intake of Nε-carboxymethyl-lysine (CML), a major AGE product, using a database of CML contents on LC-MS methods, and to examine CML's association with total and cause-specific mortality in Japanese adults. METHODS: The analysis included 13,355 men and 15,724 women, aged 35 years and older, from the Takayama study. They responded to a self-administered questionnaire in 1992. Their diet, including the CML intake, was assessed using a food-frequency questionnaire at baseline. Mortality was ascertained during 16 years of follow-up. HRs and 95% CIs for mortality were estimated separately for men and women according to CMI quartiles. RESULTS: We noted 2901 deaths in men and 2438 deaths in women during the follow-up. In men, as compared with the lowest quartile of intake, the highest quartile of CML was inversely associated with the risks of both total and non-cancer, non-cardiovascular disease mortality after controlling for covariates [HR = 0.89 (95% CI, 0.79-1.00; P-trend = 0.047) and HR = 0.74 (95% CI, 0.58-0.94; P-trend = 0.03), respectively]. However, stratified analyses showed both inverse and positive associations between CML intake and cause-specific mortality in women, depending on their characteristics. For example, years of education had a modifying effect on both the CML intake and non-cancer, non-cardiovascular disease mortality in women. In men, the associations of CML intake with mortality depended on food sources. CONCLUSIONS: Overall, the present study does not support a positive association between CML intake and mortality in Japanese adults. The potential relevance of the food source of CML to the link between dietary CML and mortality warrants further attention.