Fish and Meat Intake, Serum Eicosapentaenoic Acid and Docosahexaenoic Acid Levels, and Mortality in Community-Dwelling Japanese Older Persons
by
, and
Rei Otsuka
1,*
,
Chikako Tange
1,
Yukiko Nishita
2,
Makiko Tomida
1,
Yuki Kato
1,3,
Tomoko Imai
1,4,
Fujiko Ando
1,3 and
Hiroshi Shimokata
1,5 1
Section of NILS-LSA (National Institute for Longevity Sciences-Longitudinal Study of Aging), National Center for Geriatrics and Gerontology, Aichi 474-8511, Japan
2
Department of Epidemiology of Aging, National Center for Geriatrics and Gerontology, Aichi 474-8511, Japan
3
Faculty of Health and Medical Sciences, Aichi Shukutoku University, Aichi 480-1197, Japan
4
Faculty of Human Life and Science, Doshisha Women’s College of Liberal Arts, Kyoto 602-0893, Japan
5
Graduate School of Nutritional Sciences, Nagoya University of Arts and Sciences, Aichi 470-0196, Japan
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2019, 16(10), 1806; https://doi.org/10.3390/ijerph16101806
Submission received: 9 April 2019
/
Revised: 17 May 2019
/
Accepted: 20 May 2019
/
Published: 21 May 2019
Abstract
:The associations between meat/fish consumption, docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) intakes, and blood DHA/EPA levels, and mortality in Japan were examined as part of the National Institute for Longevity Sciences-Longitudinal Study of Aging: 520 men and 534 women (60–79 years at baseline) were followed from 1997–2017. Nutritional intakes were assessed using a 3-day dietary record and fasting venous blood samples were collected. Serum EPA/DHA concentrations, the EPA/arachidonic acid (ARA) ratio, EPA/DHA intakes, and fish/meat intakes were examined in tertiles as indicator variables, and hazard ratios (HR) were calculated to compare the risk of death across tertiles controlling for sex, age, body mass index, smoking status, alcohol drinking, physical activity, education, employment, and history of diseases. During follow-up (mean 11.7 years), 422 subjects (40.4%) died. The multivariate-adjusted HR for all-cause mortality in subjects in the highest tertile of serum DHA and EPA/ARA ratio was 0.73 (95% confidence intervals (CI): 0.53–0.99) and 0.71 (95% CI: 0.53–0.96) compared with subjects in the lowest tertile, respectively (trend p < 0.05). There were no significant associations between mortality and serum EPA/ARA and DHA/EPA intakes. An increased serum DHA level or EPA/ARA ratio might be recommended for longevity to Japanese community dwellers.
1. Introduction
Japanese individuals have a long history of eating seafood rich in n-3 polyunsaturated fatty acids (PUFAs), although nutritional intake has changed dramatically over time [1] and become more westernized [2]. Fish consumption has decreased and meat consumption has increased markedly among Japanese individuals in the last 50 to 60 years [1].
Fish consumption, particularly fatty fish, and intake of marine n-3 PUFAs (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) are thought to play a protective role against coronary heart disease (CHD) [3] and its associated mortality [4]. However, the effects of fish and n-3 PUFA consumption on mortality remain controversial [5,6,7,8]. One possible reason for inconsistent study results is the limited ability of dietary assessments to quantify blood levels of fatty acids. However, blood fatty acid biomarkers can be measured to indicate differences in delayed responses to short- and long-term dietary intakes [9,10]. A study using n-3 series PUFAs in the blood showed that higher n-3 PUFA phospholipid levels were associated with lower all-cause mortality, especially CHD deaths, in older Americans [11]. A low serum DHA, not EPA, level was associated with mortality in Japanese patients with acute decompensated heart failure [12]. However, there is little evidence concerning n-3 series PUFAs and mortality in the general Japanese population.
Mean DHA and EPA intakes and blood DHA/EPA levels are substantially higher in Japanese subjects than in Western subjects [13,14,15,16]. However, the association between blood DHA/EPA levels and mortality in Japanese subjects is unclear.
This study examined the associations of meat/fish consumption, fatty acid intakes including DHA and EPA, and blood DHA/EPA levels, concurrently, with all-cause mortality in community-dwelling Japanese older persons.
2. Materials and Methods
2.1. Participants in the Baseline Survey
Data for this survey were collected as part of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA). In this project, the normal aging process was assessed over time using detailed questionnaires and medical checkups, anthropometric measurements, physical fitness tests, and nutritional examinations. Participants in the NILS-LSA included randomly selected age- and sex-stratified individuals from a pool of non-institutionalized residents in the NCGG neighborhood areas of Obu City and Higashiura Town in the Aichi Prefecture. The first wave of the NILS-LSA was conducted from November 1997 to April 2000 and comprised of 2267 participants (1139 men, 1128 women; age range, 40–79 years). They were followed up biennially from the second study-wave (2000–2002) to the seventh study-wave (July 2010–July 2012). Details of the NILS-LSA study have been reported elsewhere [17]. The study protocol was approved by the Committee of Ethics of Human Research of the National Center for Geriatrics and Gerontology (No. 899-3). Written, informed consent was obtained from all subjects.
2.2. Follow-Up and Study Subjects
The residence records of all participants were reviewed to determine their vital status and information was obtained from the local government regarding which participants moved away from their local residence to other areas. To clarify the cause of death, the National Vital Statistics records that were available until the end of December 2017 were used. The underlying cause of death was coded according to the tenth International Classification of Diseases in 2013. Deaths were confirmed by computer matching of data from the National Vital Statistics records using neighborhood areas, sex, date of birth, and death as key codes.
Of the 2267 participants, participants aged 60 years and older at baseline (n = 1133) were selected. The following were excluded: (1) Those who fasted <12 h or were unable to supply a sufficient volume of blood (n = 20); (2) those with an energy intake less than 500 kcal/day as measured by dietary records, or no dietary records (n = 42); and (3) those who had missing data for controlled variables (n = 18). A total of 520 men and 534 women between 60 and 79 years of age at baseline were available for analysis.
2.3. Blood Sampling and Serum Fatty Acid Analysis
On enrollment in the baseline study, venous blood was collected early in the morning after fasting for at least 12 h. Blood samples were centrifuged at 3500 × g for 15 min. The serum was refrigerated before analysis for fatty acid content. Serum DHA, EPA, and arachidonic acid (ARA) concentrations were measured by gas-liquid chromatography at a clinical laboratory (SRL, Tokyo, Japan). Briefly, total lipids in the serum were extracted using the Folch procedure, and fatty acids were then methylated with BF3/methanol. Transesterified fatty acids were then analyzed using a gas chromatograph (GC-17A; Shimadzu, Kyoto, Japan) with a capillary column (Omegawax 250; Supelco, Bellefonte, PA, USA). The weights of DHA and EPA (g/mL) as fatty acid concentrations were identified by comparison with known standards. Intra- and inter-assay precision and accuracy values (coefficient of variation [CV]) were 3.2 and 5.8 CV% for ARA, 2.7 and 6.9 CV% for EPA, and 1.9 and 6.9 CV% for DHA, respectively [18]. In the statistical analyses, serum EPA, DHA, ARA concentrations, and the EPA/ARA ratio, which predict future cardiovascular events [19], were selected as serum fatty acid factors.
2.4. Nutritional Assessments
Nutritional intakes were assessed using a 3-day dietary record without any supplements after participation in the baseline study. The dietary record was completed over 3 continuous days (2 weekdays and 1 weekend day) [19], and most subjects completed it at home and returned records within 1 month. Food was weighed separately on a scale (1-kg kitchen scales; Sekisui Jushi, Tokyo, Japan) before being cooked, or portion sizes were estimated. Subjects used a disposable camera (27 shots; Fuji Film, Tokyo, Japan) to take photos of meals before and after eating. Dietitians used these photos to complete missing data and telephoned subjects to resolve any discrepancies or obtain further information when necessary. Averages for 3-day food and nutrient intakes (including alcohol intake) were calculated according to the Standard Tables of Foods Composition in Japan 2010 and other sources [20,21].
2.5. Other Measurements
History of diseases, education (≤9, 10–12, or ≥13 years of school), employment (unemployed, regular employment, or non-regular employment), and smoking status (yes/no) were collected using self-reported questionnaires, and medical doctors or trained staff confirmed the information. Concerning diseases, information about past and current cancer, heart disease, stroke, hypertension, dyslipidemia, and diabetes mellitus was collected in 4 categories: (1) None; (2) on medication; (3) previously medicated; and (4) not treated. These illnesses were then re-categorized into 2 categories (yes or no; yes included (2) on medication, (3) previously medicated, and (4) not treated, and no included (1) none).
Body mass index (BMI) was calculated as weight in kilograms divided by the square of the height in meters. Physical activity was assessed by the metabolic equivalents (METs) score (a multiple of the resting metabolic rate), with participants interviewed by trained interviewers using a semi-quantitative assessment method to assess participants’ levels of habitual physical activity during leisure time, on the job, and sleeping hours [22]. These measurements were assessed in the baseline survey.
2.6. Statistical Analysis
Fish and meat intakes, fatty acid intakes including EPA, DHA, and ARA, and serum EPA, DHA, ARA concentrations, and the EPA/ARA ratio were examined in sex-stratified tertiles as indicator variables. Men generally consume more food than women, and the ratio of men would be higher in higher intake groups (i.e., higher tertiles) if tertiles were calculated with men and women together; therefore, sex-stratified tertiles were calculated for each explanatory variable.
The relationships of fish and meat intakes, EPA and DHA intakes, serum EPA, DHA, and ARA concentrations, and the EPA/ARA ratio with the survival rate (all-cause mortality) were assessed using Kaplan–Meier survival curves (Supplementary Figures S1 and S2). The hazard ratios (HR) and 95% confidence intervals (CI) for outcomes were calculated by tertiles using a Cox proportional hazards model. Tests for trends were based on modeling in each tertile category. Follow-up time (years) was calculated by the length of time (days) that had elapsed since the day each subject participated in the baseline study. The end point of the study was calculated as the time at death or the latest date of the adjudicated follow-up. The confounding variables were sex, age, BMI, smoking status, alcohol drinking, physical activity, education, employment, and history of cancer, heart disease, stroke, hypertension, dyslipidemia, and diabetes mellitus.
Based on the main results (i.e., the significant association between serum DHA and mortality), differences in proportions according to tertiles of serum DHA concentrations were assessed using the χ2 test. Comparisons between continuous variables according to tertiles of serum DHA concentrations were performed by one-way analysis of variance. The Tukey test was used to adjust for multiple comparisons.
All reported p values are two-sided, and a p value less than 0.05 was considered significant. All statistical analyses were conducted using Statistical Analysis System software version 9.3 (SAS Institute, Cary, NC, USA).
3. Results
During the follow-up from the baseline survey to December 2017, 422 subjects (40.4%) died; their mean (standard deviation (SD)) follow-up was 11.7 (4.8) years, whereas that of the survivors was 17.8 (3.2) years. Of the 422 deaths, 31.3% (n = 132) were caused by cancer, 14.2% (n = 60) by heart disease, and 11.4% (n = 47) by stroke.
Table 1 shows the baseline characteristics of the participants. More than 37% of subjects had a history of hypertension and more than 21% of subjects had a history of dyslipidemia. Mean (SD) daily fish, meat, EPA, and DHA intakes were 98.8 (50.5) g, 51.0 (31.7) g, 319.1 (240.3) mg, and 569.4 (382.5) mg, respectively.
Table 2 shows the multivariate-adjusted HR for all-cause mortality of fish, meat, and fatty acid intakes. Although there were no significant associations, the HR for mortality of the middle and highest tertiles of fatty acid intake were 0.80 (95% CI: 0.59–1.08) and 0.74 (95% CI: 0.55–1.01), respectively, compared with the lowest tertile of fatty acid intake. The HR for mortality of the highest tertile of saturated fatty acid intake was 0.73 (95% CI: 0.53–0.99) compared with the lowest tertile of saturated fatty acid intake (trend p < 0.05). Fish, meat, and unsaturated fatty acid intakes, including EPA and DHA intakes, were not associated with mortality.
Multivariate-adjusted HR for all-cause mortality according to serum EPA, DHA, ARA, and the EPA/ARA ratio are shown in Table 3. Although there were no significant associations between mortality and serum EPA and ARA, the HR for mortality of the highest tertile of serum DHA was 0.73 (95% CI: 0.53–0.99) compared with the lowest tertile of serum DHA. In addition, the HR for mortality of the highest tertile of the serum EPA/ARA ratio was 0.71 (95% CI: 0.53–0.96) compared with the lowest tertile of the serum EPA/ARA ratio.
Table 4 shows the baseline characteristics of the participants by tertiles of serum DHA. Subjects with higher serum DHA levels were more likely to have a higher BMI and to consume more fish, DHA, EPA, and ARA in their diet. On the other hand, those with higher serum DHA levels were less likely to engage in physical activity.
4. Discussion
These results suggest the beneficial effect of higher serum DHA levels on all-cause mortality in Japanese older persons whose DHA and EPA intake/serum DHA and EPA levels are higher than those of Western people. On the other hand, fish, meat, EPA, and DHA intakes were not associated with mortality.
Many previous studies have focused on fish and meat consumption and health outcomes such as breast cancer [23], pancreatic cancer [24], and cerebrovascular disease mortality [25]. One study suggested that both meat and fish intake reduced the incidence of cerebrovascular disease in Japanese persons [25]. On the other hand, a meta-analysis indicated that consumption of red and/or processed meat increased the risk of stroke [26], and consumption of processed meat increased the risk of CHD [27]. Meat is a major source of protein for humans, but saturated fatty acids contained in raw meat or sodium in processed meat are thought to have a negative effect on coronary artery disease [28]. In the present study, fatty acid intake, especially saturated fatty acid intake, was negatively associated with mortality, but meat was not associated with mortality.
Meta-analyses of 12 prospective cohort studies reported that the saturated fat intake was not associated with all-cause mortality [29]. Another prospective cohort study conducted in 18 countries reported that total fat and each type of fat, including saturated fatty acid, intake were associated with lower all-cause mortality [30]. They suggested that the reasons for the negative association between fat intake and mortality depended on the study population. In that study [30], more than half of the participants consumed a high carbohydrate diet (at least 60% of energy), the subjects lived mainly in Asia, and the percentage was higher than in most previous studies done in North America and Europe. In the present study, Japanese participants also consumed a high carbohydrate diet (mean: 58.7% of energy, data not shown), therefore, the results of the negative association between saturated fatty acid intake and mortality are consistent in Asian people. In other words, the results indicated that higher saturated fatty acid intake in Asian people was not necessarily associated with a higher risk of mortality.
In the present study, higher serum DHA levels (p trend = 0.047) and a higher serum EPA/ARA ratio (p trend = 0.02) were negatively associated with all-cause mortality, though higher serum EPA levels were not significantly negatively associated with mortality. DHA and EPA are thought to be important for the prevention of cardiovascular disease, and DHA has effects on membrane properties and cell signaling [31], whereas EPA has a more pronounced effect on eicosanoid production [32]. In a previous study, low serum DHA, not EPA, was associated with mortality in Japanese patients with acute decompensated heart failure [12]. In addition, a meta-analysis of general populations including the Japanese reported that n-3 polyunsaturated fatty acid intake as well as blood DHA and EPA were negatively associated with mortality [33]. Among Japanese patients undergoing percutaneous coronary intervention, the higher serum EPA/ARA ratio group (>0.40) had a significantly lower incidence of major cardiac events than the lower EPA/ARA ratio group (≤0.40) [19]. In the present study, the median values of the first (lower) and second (middle) tertiles in the serum EPA/ARA ratio group were 0.3 and 0.4, respectively. The precise mechanism was unknown, but the blood level of DHA and the EPA/ARA ratio might be protective factors for longevity through membrane properties, cell signaling, and lower cardiac events.
There were no positive associations between DHA and EPA intakes and the risk of mortality. The lack of findings might be caused by difficulties with dietary assessments. Japanese people usually eat one or two fish dishes per day, and the median intake/day of subjects in the present study was 90 g for fish and 48 g for meat. Even if the Japanese consume fish daily, within individual variations of n-3 PUFAs such as EPA or DHA that were high, and the accuracy of n-3 PUFA values assessed by 3-day dietary records was estimated to have a 28% coefficient of variation among Japanese people [34]. The limited ability of dietary assessments to quantify blood levels of fatty acids is a major possible reason for previous inconsistent results regarding n-3 PUFA consumption and risk of mortality [5,6,7,8]. Another possible reason could be confounding factors such as high blood pressure or cardiovascular disease. In the present study, adjustments were made for many variables, including cancer, heart disease, stroke, hypertension, dyslipidemia, and diabetes mellitus, and that might have led to over-adjustment. More precise and careful control of confounders may be necessary.
Several limitations to the present study warrant consideration. Dietary factors and serum fatty acid levels were assessed from one nutritional assessment and a single blood sampling at baseline. Food intake is easily changeable and affected by various factors with aging [35,36], though these variations could not be considered during the follow-up period. In addition, the number of cause-specific deaths was not large, and no significant associations were found between the serum DHA level and cause-specific disease mortality (data not shown). Larger prospective studies are needed to examine these fatty acids and cause-specific disease mortality. In addition, attrition bias may have attenuated the results. Furthermore, since DHA and EPA intakes/serum levels are substantially higher in Japanese than in Western subjects [13], prudent interpretation of the results is needed (i.e., low DHA/EPA levels among Japanese subjects might not mean low levels among Western subjects). Thus, the results of this study cannot necessarily be applied to Western populations.
In previous reports, we showed the positive correlations between serum DHA composition and DHA intake in the same cohort study [37]. In the present study, although there was no negative association between fish/DHA intake and mortality, intake of more fish/DHA would increase serum DHA levels.
5. Conclusions
The findings of this study indicate that an increase in serum DHA levels or the EPA/ARA ratio might be recommended for longevity to Japanese community dwellers.
Supplementary Materials
The following are available online at https://www.mdpi.com/1660-4601/16/10/1806/s1, Figure S1: Survival curves according to tertiles of fish, meat, DHA, and EPA intake, Figure S2: Survival curves according to tertiles of serum DHA, EPA, ARA, and the EPA/ARA ratio.
Author Contributions
Conceptualization, R.O.; methodology, R.O.; formal analysis, R.O.; investigation, R.O., Y.K., T.I., C.T., Y.N., M.T., F.A., H.S.; writing—original draft preparation, R.O.; writing—review and editing, Y.K., T.I., C.T., Y.N., M.T., F.A., H.S.; supervision, F.A., and H.S.; project administration, F.A., and H.S.; funding acquisition, R.O., H.S.
Funding
This work was supported in part by grants from the Research Funding for Longevity Sciences from the National Center for Geriatrics and Gerontology, Japan (grant numbers 28-40 and 19-10). All grantors had no role in the design, analysis, or writing of this article.
Acknowledgments
The authors wish to express their sincere appreciation to the study participants and their colleagues in the NILS-LSA for completing the survey for this study.
Conflicts of Interest
The authors declare no conflict of interest.
References
- Katanoda, K.; Matsumura, Y. National Nutrition Survey in Japan--its methodological transition and current findings. J. Nutr. Sci. Vitaminol. 2002, 48, 423–432. [Google Scholar] [CrossRef] [PubMed]
- Annual Report of the National Nutrition Survey in 2012. Available online: http://www.mhlw.go.jp/bunya/kenkou/eiyou/h24-houkoku.html (accessed on 13 March 2019). (In Japanese).
- Sekikawa, A.; Steingrimsdottir, L.; Ueshima, H.; Shin, C.; Curb, J.D.; Evans, R.W.; Hauksdottir, A.M.; Kadota, A.; Choo, J.; Masaki, K.; et al. Serum levels of marine-derived n-3 fatty acids in Icelanders, Japanese, Koreans, and Americans--a descriptive epidemiologic study. Prostaglandins Leukot. Essent. Fat. Acids 2012, 87, 11–16. [Google Scholar] [CrossRef] [PubMed]
- Crombie, I.K.; McLoon, P.; Smith, W.C.; Thomson, M.; Pedoe, H.T. International differences in coronary heart disease mortality and consumption of fish and other foodstuffs. Eur. Heart J. 1987, 8, 560–563. [Google Scholar] [CrossRef] [PubMed]
- León, H.; Shibata, M.C.; Sivakumaran, S.; Dorgan, M.; Chatterley, T.; Tsuyuki, R.T. Effect of fish oil on arrhythmias and mortality: Systematic review. BMJ 2008, 337, a2931. [Google Scholar] [CrossRef]
- Nakamura, Y.; Ueshima, H.; Okamura, T.; Kadowaki, T.; Hayakawa, T.; Kita, Y.; Tamaki, S.; Okayama, A.; NIPPON DATA80 Research Group. Association between fish consumption and all-cause and cause-specific mortality in Japan: NIPPON DATA80, 1980–1999. Am. J. Med. 2005, 118, 239–245. [Google Scholar] [CrossRef] [PubMed]
- Zhang, J.; Sasaki, S.; Amano, K.; Kesteloot, H. Fish consumption and mortality from all causes, ischemic heart disease, and stroke: An ecological study. Prev. Med. 1999, 28, 520–529. [Google Scholar] [CrossRef]
- Osler, M.; Andreasen, A.H.; Hoidrup, S. No inverse association between fish consumption and risk of death from all-causes, and incidence of coronary heart disease in middle-aged, Danish adults. J. Clin. Epidemiol. 2003, 56, 274–279. [Google Scholar] [CrossRef]
- Frank, B.H. Obesity Epidemiology; Oxford University Press: New York, NY, USA, 2008. [Google Scholar]
- Kobayashi, M.; Sasaki, S.; Kawabata, T.; Hasegawa, K.; Akabane, M.; Tsugane, S. Single measurement of serum phospholipid fatty acid as a biomarker of specific fatty acid intake in middle-aged Japanese men. Eur. J. Clin. Nutr. 2001, 55, 643–650. [Google Scholar] [CrossRef] [Green Version]
- Mozaffarian, D.; Lemaitre, R.N.; King, I.B.; Song, X.; Huang, H.; Sacks, F.M.; Rimm, E.B.; Wang, M.; Siscovick, D.S. Plasma phospholipid long-chain omega-3 fatty acids and total and cause-specific mortality in older adults: A cohort study. Ann. Intern. Med. 2013, 158, 515–525. [Google Scholar] [CrossRef]
- Ouchi, S.; Miyazaki, T.; Shimada, K.; Sugita, Y.; Shimizu, M.; Murata, A.; Kato, T.; Aikawa, T.; Suda, S.; Shiozawa, T.; et al. Low docosahexaenoic acid, dihomo-gamma-linolenic acid, and arachidonic acid levels associated with long-term mortality in patients with acute decompensated heart failure in different nutritional statuses. Nutrients 2017, 30, 9. [Google Scholar]
- Kuriki, K.; Nagaya, T.; Tokudome, Y.; Imaeda, N.; Fujiwara, N.; Sato, J.; Goto, C.; Ikeda, M.; Maki, S.; Tajima, K.; et al. Plasma concentrations of (n-3) highly unsaturated fatty acids are good biomarkers of relative dietary fatty acid intakes: A cross-sectional study. J. Nutr. 2003, 133, 3643–3650. [Google Scholar] [CrossRef] [PubMed]
- Sugano, M.; Hirahara, F. Polyunsaturated fatty acids in the food chain in Japan. Am. J. Clin. Nutr. 2000, 71, 189S–196S. [Google Scholar] [CrossRef]
- Farina, E.K.; Kiel, D.P.; Roubenoff, R.; Schaefer, E.J.; Cupples, L.A.; Tucker, K.L. Protective effects of fish intake and interactive effects of long-chain polyunsaturated fatty acid intakes on hip bone mineral density in older adults: The Framingham Osteoporosis Study. Am. J. Clin. Nutr. 2011, 93, 1142–1151. [Google Scholar] [CrossRef]
- Ma, J.; Folsom, A.R.; Shahar, E.; Eckfeldt, J.H. Plasma fatty acid composition as an indicator of habitual dietary fat intake in middle-aged adults. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Am. J. Clin. Nutr. 1995, 62, 564–571. [Google Scholar] [CrossRef] [PubMed]
- Shimokata, H.; Ando, F.; Niino, N. A new comprehensive study on aging--the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA). J. Epidemiol. 2000, 10, S1–S9. [Google Scholar] [CrossRef] [PubMed]
- Otsuka, R.; Kato, Y.; Imai, T.; Ando, F.; Shimokata, H. Secular trend of serum docosahexaenoic acid, eicosapentaenoic acid, and arachidonic acid concentrations among Japanese-a 4- and 13-year descriptive epidemiologic study. Prostaglandins Leukot. Essent. Fat. Acids 2015, 94, 35–42. [Google Scholar] [CrossRef] [PubMed]
- Domei, T.; Kuramitsu, S.; Soga, Y.; Arita, T.; Ando, K.; Shirai, S.; Kondo, K.; Sakai, K.; Goya, M.; Iwabuchi, M.; et al. Ratio of serum n-3 to n-6 polyunsaturated fatty acids and the incidence of major adverse cardiac events in patients undergoing percutaneous coronary intervention. Circ. J. 2011, 76, 423–429. [Google Scholar] [CrossRef] [PubMed]
- Imai, T.; Sakai, S.; Mori, K.; Ando, F.; Niino, N.; Shimokata, H. Nutritional assessments of 3-day dietary records in National Institute for Longevity Sciences--Longitudinal Study of Aging (NILS-LSA). J. Epidemiol. 2000, 10, S70–S76. [Google Scholar] [CrossRef] [PubMed]
- Ministry of Education Culture, Sports, Science and Technology. Standard Tables of Food Composition in Japan 2010. Available online: http://www.mext.go.jp/b_menu/shingi/gijyutu/gijyutu3/houkoku/1298713.htm (accessed on 13 March 2019).
- Kozakai, R.; Ando, F.; Kim, H.Y.; Rantanen, T.; Shimokata, H. Regular exercise history as a predictor of exercise in community-dwelling older Japanese people. J. Phys. Fit. Sports Med. 2012, 1, 167–174. [Google Scholar] [CrossRef] [Green Version]
- Holmes, M.D.; Colditz, G.A.; Hunter, D.J.; Hankinson, S.E.; Rosner, B.; Speizer, F.E.; Willett, W.C. Meat, fish and egg intake and risk of breast cancer. Int. J. Cancer 2003, 104, 221–227. [Google Scholar] [CrossRef]
- Larsson, S.C.; Håkanson, N.; Permert, J.; Wolk, A. Meat, fish, poultry and egg consumption in relation to risk of pancreatic cancer: A prospective study. Int. J. Cancer 2006, 118, 2866–2870. [Google Scholar] [CrossRef]
- Kinjo, Y.; Beral, V.; Akiba, S.; Key, T.; Mizuno, S.; Appleby, P.; Yamaguchi, N.; Watanabe, S.; Doll, R. Possible protective effect of milk, meat and fish for cerebrovascular disease mortality in Japan. J. Epidemiol. 1999, 9, 268–274. [Google Scholar] [CrossRef]
- Chen, G.C.; Lv, D.B.; Pang, Z.; Liu, Q.F. Red and processed meat consumption and risk of stroke: A meta-analysis of prospective cohort studies. Eur. J. Clin. Nutr. 2013, 67, 91–95. [Google Scholar] [CrossRef] [PubMed]
- Micha, R.; Wallace, S.K.; Mozaffarian, D. Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes mellitus: A systematic review and meta-analysis. Circulation 2010, 121, 2271–2283. [Google Scholar] [CrossRef]
- Micha, R.; Michas, G.; Mozaffarian, D. Unprocessed red and processed meats and risk of coronary artery disease and type 2 diabetes--an updated review of the evidence. Curr. Atheroscler. Rep. 2012, 14, 515–524. [Google Scholar] [CrossRef]
- De Souza, R.J.; Mente, A.; Maroleanu, A.; Cozma, A.I.; Ha, V.; Kishibe, T.; Uleryk, E.; Budylowski, P.; Schünemann, H.; Beyene, J.; et al. Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: Systematic review and meta-analysis of observational studies. BMJ 2015, 11, h3978. [Google Scholar] [CrossRef] [PubMed]
- Dehghan, M.; Mente, A.; Zhang, X.; Swaminathan, S.; Li, W.; Mohan, V.; Iqbal, R.; Kumar, R.; Wentzel-Viljoen, E.; et al. Prospective Urban Rural Epidemiology (PURE) study investigators. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): A prospective cohort study. Lancet 2017, 390, 2050–2062. [Google Scholar] [CrossRef]
- Salem, N., Jr.; Litman, B.; Kim, H.Y.; Gawrisch, K. Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids 2001, 36, 945–959. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bakewell, L.; Burdge, G.C.; Calder, P.C. Polyunsaturated fatty acid concentrations in young men and women consuming their habitual diets. Br. J. Nutr. 2006, 96, 93–99. [Google Scholar] [CrossRef]
- Chen, G.C.; Yang, J.; Eggersdorfer, M.; Zhang, W.; Qin, L.Q. N-3 long-chain polyunsaturated fatty acids and risk of all-cause mortality among general populations: A meta-analysis. Sci. Rep. 2016, 16, 28165. [Google Scholar] [CrossRef]
- Sasaki, S. Introductory Guide of Dietary Reference Intakes―Sono Kokoro Wo Yomu; Dobunshoin: Tokyo, Japan, 2010. (In Japanese) [Google Scholar]
- Wakimoto, P.; Block, G. Dietary intake, dietary patterns, and changes with age: An epidemiological perspective. J. Gerontol. A Biol. Sci. Med. Sci. 2001, 56, 65–80. [Google Scholar] [CrossRef] [PubMed]
- Zhu, K.; Devine, A.; Suleska, A.; Tan, C.Y.; Toh, C.Z.; Kerr, D.; Prince, R.L. Adequacy and change in nutrient and food intakes with aging in a seven-year cohort study in elderly women. J. Nutr. Health Aging 2010, 14, 723–729. [Google Scholar] [CrossRef] [PubMed]
- Otsuka, R.; Kato, Y.; Imai, T.; Ando, F.; Shimokata, H. Higher serum EPA or DHA, and lower ARA compositions with age independent fatty acid intake in Japanese aged 40 to 79. Lipids 2013, 48, 719–727. [Google Scholar] [CrossRef] [PubMed]
Table 1.
Baseline characteristics of participants (n = 1054).
| Characteristics | Range | |||
|---|---|---|---|---|
| Min | Max | Mean | SD | |
| Men (n, %) | - | 520, 49.3 | ||
| Age (years) | 60 | 79 | 68.6 | 5.5 |
| Body mass index (kg/m2) | 14.1 | 42.4 | 22.9 | 3.1 |
| Alcohol (mL/day) | 0 | 116.7 | 7.5 | 13.9 |
| Physical activity (1000 METs × h/day) | 26.6 | 62.8 | 34.5 | 3.8 |
| Current smoker (n, %) | - | 186, 17.7 | ||
| Education | ||||
| ≤ 9 years (n, %) | - | 507, 48.1 | ||
| 10–12 years (n, %) | - | 379, 36.0 | ||
| ≥ 13 years (n, %) | - | 168, 15.9 | ||
| Employment | ||||
| Unemployed (n, %) | - | 733, 69.5 | ||
| Regular employment (n, %) | - | 201, 19.1 | ||
| Non-regular employment (n, %) | - | 120, 11.4 | ||
| Diseases | ||||
| Cancer (n, %) | - | 58, 5.5 | ||
| Heart disease (n, %) | - | 181, 17.2 | ||
| Stroke (n, %) | - | 49, 7.1 | ||
| Hypertension (n, %) | - | 394, 37.4 | ||
| Dyslipidemia (n, %) | - | 228, 21.6 | ||
| Diabetes (n, %) | - | 119, 11.3 | ||
| Dietary intake | ||||
| Fish intake (g/day) | 0.0 | 346.2 | 98.8 | 50.5 |
| Meat intake (g/day) | 0.0 | 222.7 | 51.0 | 31.7 |
| EPA intake (mg/day) | 6.6 | 1638.8 | 319.1 | 240.3 |
| DHA intake (mg/day) | 23.0 | 2722.5 | 569.4 | 382.5 |
| ARA intake (mg/day) | 18.9 | 541.5 | 167.4 | 64.9 |
| Serum fatty acid | ||||
| EPA (μg/mL) | 5.8 | 269.1 | 70.7 | 37.0 |
| DHA (μg/mL) | 30.2 | 460.6 | 152.5 | 47.1 |
| ARA (μg/mL) | 61.8 | 337.4 | 149.2 | 35.9 |
| EPA/ARA ratio | 0.1 | 2.3 | 0.5 | 0.3 |
Min, minimum; Max, maximum; SD, standard deviation; METs, metabolic equivalents; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; ARA, arachidonic acid.
Table 2.
Multivariate-adjusted hazard ratios 1 for all-cause mortality of fish, meat, and fatty acid intakes (n = 1054).
Table 2.
Multivariate-adjusted hazard ratios 1 for all-cause mortality of fish, meat, and fatty acid intakes (n = 1054).
| Explanatory Variable | Tertile 1 | Tertile 2 | Tertile 3 | p trend | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Median | Cases n /Alive n | HR (ref) | Median | Cases n /Alive n | HR (95% CI) | Median | Cases n /Alive n | HR (95% CI) | |||||
| Fish intake | 55.0 | g/day | 142/208 | 1 | 89.5 | g/day | 142/208 | 1.16 (0.85–1.58) | 141.4 | g/day | 138/216 | 1.20 (0.89–1.63) | 0.23 |
| Meat intake | 20.0 | g/day | 159/188 | 1 | 46.7 | g/day | 136/215 | 0.77 (0.57–1.03) | 80.0 | g/day | 127/229 | 0.81 (0.60–1.11) | 0.19 |
| Fatty acid intake | 31.9 | g/day | 171/179 | 1 | 43.5 | g/day | 134/217 | 0.80 (0.59–1.08) | 57.2 | g/day | 117/236 | 0.74 (0.55–1.01) | 0.06 |
| Saturated fatty acid intake | 9.7 | g/day | 160/190 | 1 | 14.0 | g/day | 143/208 | 0.75 (0.55–1.01) | 19.5 | g/day | 119/234 | 0.73 (0.53–0.99) | 0.04 |
| Unsaturated fatty acid intake | 21.2 | g/day | 171/179 | 1 | 29.2 | g/day | 134/217 | 0.72 (0.53–0.97) | 38.9 | g/day | 117/236 | 0.78 (0.57–1.05) | 0.10 |
| n-6 polyunsaturated fatty acid intake | 6.8 | g/day | 160/190 | 1 | 9.6 | g/day | 140/211 | 0.69 (0.50–0.93) | 12.6 | g/day | 122/231 | 0.80 (0.59–1.07) | 0.13 |
| ARA intake | 104.4 | mg/day | 159/191 | 1 | 159.0 | mg/day | 134/217 | 0.98 (0.73–1.33) | 226.1 | mg/day | 129/224 | 0.95 (0.69–1.30) | 0.74 |
| n-3 polyunsaturated fatty acid intake | 1.5 | g/day | 166/184 | 1 | 2.2 | g/day | 122/229 | 0.77 (0.57–1.05) | 3.3 | g/day | 134/219 | 0.83 (0.61–1.12) | 0.22 |
| EPA intake | 101.7 | mg/day | 162/188 | 1 | 268.8 | mg/day | 120/231 | 0.85 (0.63–1.16) | 530.3 | mg/day | 140/213 | 0.96 (0.71–1.30) | 0.78 |
| DHA intake | 226.1 | mg/day | 160/190 | 1 | 499.4 | mg/day | 130/221 | 0.85 (0.62–1.16) | 864.2 | mg/day | 132/221 | 0.95 (0.70–1.28) | 0.72 |
1 HR adjusted for sex, baseline age, body mass index, smoking status, alcohol drinking, physical activity, education, employment, and history of cancer, heart disease, stroke, hypertension, dyslipidemia, and diabetes mellitus. HR, hazard ratios; CI, confidence intervals; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; ARA, arachidonic acid.
Table 3.
Multivariate-adjusted hazard ratios 1 for all-cause mortality of serum EPA, DHA, and ARA (n = 1054).
Table 3.
Multivariate-adjusted hazard ratios 1 for all-cause mortality of serum EPA, DHA, and ARA (n = 1054).
| Explanatory Variable | Tertile 1 | Tertile 2 | Tertile 3 | p trend | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Median | Cases n /Alive n | HR (ref) | Median | Cases n /Alive n | HR (95% CI) | Median | Cases n /Alive n | HR (95% CI) | |||||
| Serum EPA | 38.1 | μg/mL | 150/200 | 1 | 62.9 | μg/mL | 133/218 | 0.82 (0.61–1.10) | 101.9 | μg/mL | 139/214 | 0.81 (0.60–1.09) | 0.17 |
| Serum DHA | 111.6 | μg/mL | 151/197 | 1 | 147.1 | μg/mL | 143/210 | 0.82 (0.61–1.10) | 191.0 | μg/mL | 128/225 | 0.73 (0.53–0.99) | 0.047 |
| Serum ARA | 116.7 | μg/mL | 136/213 | 1 | 144.0 | μg/mL | 156/195 | 1.47 (1.10–1.98) | 184.2 | μg/mL | 130/224 | 0.90 (0.64–1.24) | 0.51 |
| Serum EPA/ARA | 0.3 | 141/212 | 1 | 0.4 | 128/223 | 0.62 (0.45–0.84) | 0.7 | 141/212 | 0.71 (0.53–0.96) | 0.02 | |||
1 HR adjusted for sex, baseline age, body mass index, smoking status, alcohol drinking, physical activity, education, employment, and history of cancer, heart disease, stroke, hypertension, dyslipidemia, and diabetes mellitus. HR, hazard ratios; CI, confidence intervals; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; ARA, arachidonic acid.
Table 4.
Baseline characteristics of participants by tertiles of serum DHA (n = 1054).
| Characteristics | Tertile 1 | Tertile 2 | Tertile 3 | p1 | p2 | |||
|---|---|---|---|---|---|---|---|---|
| Mean | SD | Mean | SD | Mean | SD | |||
| Number of subjects | 348 | 353 | 353 | |||||
| Serum DHA (μg/mL) | 108.0 | 17.4 | 146.5 | 10.4 | 202.3 | 41.8 | <0.0001 | *, **, *** |
| Men (n, %) | 172, 49.3 | 174, 49.3 | 174, 49.3 | 0.99 | ||||
| Age (years) | 68.9 | 5.4 | 68.6 | 5.6 | 68.4 | 5.4 | 0.47 | |
| Body mass index (kg/m2) | 22.7 | 3.1 | 22.6 | 3.4 | 23.3 | 2.9 | 0.01 | *, ** |
| Alcohol (mL/day) | 6.3 | 12.9 | 7.5 | 13.8 | 8.7 | 14.8 | 0.08 | |
| Physical activity (1000 METs × h/day) | 34.8 | 3.9 | 34.6 | 4.0 | 34.0 | 3.3 | 0.01 | ** |
| Current smoker (n, %) | 59, 17.0 | 70, 19.8 | 57, 16.2 | 0.40 | ||||
| Education | ||||||||
| ≤ 9 years (n, %) | 175, 50.3 | 171, 49.3 | 158, 44.8 | 0.48 | ||||
| 10–12 years (n, %) | 121, 34.8 | 119, 33.7 | 139, 39.4 | |||||
| ≥ 13 years (n, %) | 52, 14.9 | 60, 17.0 | 56, 15.9 | |||||
| Employment | ||||||||
| Unemployed (n, %) | 240, 69.0 | 245, 69.4 | 248, 70.3 | 0.94 | ||||
| Regular employment (n, %) | 69, 19.8 | 63, 17.9 | 69, 19.6 | |||||
| Non-regular employment (n, %) | 39, 11.2 | 45, 12.8 | 36, 10.2 | |||||
| Diseases | ||||||||
| Cancer (n, %) | 23, 6.6 | 19, 5.4 | 16, 4.6 | 0.49 | ||||
| Heart disease (n, %) | 64, 18.4 | 62, 17.6 | 55, 15.6 | 0.60 | ||||
| Stroke (n, %) | 16, 6.9 | 12, 5.0 | 21, 9.4 | 0.19 | ||||
| Hypertension (n, %) | 128, 36.8 | 123, 34.8 | 143, 40.5 | 0.29 | ||||
| Dyslipidemia (n, %) | 54, 15.5 | 67, 19.0 | 107, 30.3 | <0.0001 | ||||
| Diabetes (n, %) | 41, 11.8 | 35, 9.9 | 43, 12.2 | 0.60 | ||||
| Dietary intake | ||||||||
| Fish intake (g/day) | 89.0 | 46.5 | 96.3 | 44.5 | 110.8 | 57.1 | <0.0001 | *, ** |
| Meat intake (g/day) | 49.4 | 29.6 | 51.3 | 32.7 | 52.1 | 32.7 | 0.52 | |
| EPA intake (mg/day) | 276.6 | 220.9 | 304.9 | 202.7 | 375.4 | 280.0 | <0.0001 | *, ** |
| DHA intake (mg/day) | 500.8 | 338.2 | 547.8 | 332.8 | 658.7 | 448.3 | <0.0001 | *, ** |
| ARA intake (mg/day) | 158.3 | 59.2 | 165.8 | 60.1 | 178.1 | 73.1 | <0.001 | *, ** |
1 For continuous variables, one-way analysis of variance was used; for categorical variables, the χ2 test was used. 2 For continuous variables, the Tukey test was used for multiple comparisons (* Tertile 1 vs. Tertile 2 p < 0.05, ** Tertile 1 vs. Tertile 3 p < 0.05, *** Tertile 2 vs. Tertile 3 p < 0.05). DHA, docosahexaenoic acid; SD, standard deviation; METs, metabolic equivalents; EPA, eicosapentaenoic acid; ARA, arachidonic acid.
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
MDPI and ACS Style
Otsuka, R.; Tange, C.; Nishita, Y.; Tomida, M.; Kato, Y.; Imai, T.; Ando, F.; Shimokata, H. Fish and Meat Intake, Serum Eicosapentaenoic Acid and Docosahexaenoic Acid Levels, and Mortality in Community-Dwelling Japanese Older Persons. Int. J. Environ. Res. Public Health 2019, 16, 1806. https://doi.org/10.3390/ijerph16101806
AMA Style
Otsuka R, Tange C, Nishita Y, Tomida M, Kato Y, Imai T, Ando F, Shimokata H. Fish and Meat Intake, Serum Eicosapentaenoic Acid and Docosahexaenoic Acid Levels, and Mortality in Community-Dwelling Japanese Older Persons. International Journal of Environmental Research and Public Health. 2019; 16(10):1806. https://doi.org/10.3390/ijerph16101806
Chicago/Turabian StyleOtsuka, Rei, Chikako Tange, Yukiko Nishita, Makiko Tomida, Yuki Kato, Tomoko Imai, Fujiko Ando, and Hiroshi Shimokata. 2019. "Fish and Meat Intake, Serum Eicosapentaenoic Acid and Docosahexaenoic Acid Levels, and Mortality in Community-Dwelling Japanese Older Persons" International Journal of Environmental Research and Public Health 16, no. 10: 1806. https://doi.org/10.3390/ijerph16101806
APA StyleOtsuka, R., Tange, C., Nishita, Y., Tomida, M., Kato, Y., Imai, T., Ando, F., & Shimokata, H. (2019). Fish and Meat Intake, Serum Eicosapentaenoic Acid and Docosahexaenoic Acid Levels, and Mortality in Community-Dwelling Japanese Older Persons. International Journal of Environmental Research and Public Health, 16(10), 1806. https://doi.org/10.3390/ijerph16101806
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.
