Association of fatty acid consumption with frailty and mortality among middle-aged and older adults

Association of fatty acid consumption with frailty and mortality among middle-aged and older adults

Nutrition 70 (2020) 110610 Contents lists available at ScienceDirect Nutrition journal homepage: www.nutritionjrnl.com Applied nutritional investig...

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Nutrition 70 (2020) 110610

Contents lists available at ScienceDirect

Nutrition journal homepage: www.nutritionjrnl.com

Applied nutritional investigation

Association of fatty acid consumption with frailty and mortality among middle-aged and older adults Kulapong Jayanama M.D. a,b, Olga Theou Ph.D. a,c,*, Judith Godin Ph.D. a, Leah Cahill Ph.D. c,d, Kenneth Rockwood M.D. a,c a

Division of Geriatric Medicine, Dalhousie University & Nova Scotia Health Authority, Halifax, Nova Scotia, Canada Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada d Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA b c

A R T I C L E

I N F O

Article History: Received 18 May 2019 Received in revised form 17 July 2019 Accepted 23 September 2019 Keywords: Fatty acids Nutrition Nutrition index Frailty Frailty index Mortality NHANES

A B S T R A C T

Objectives: Despite their role in health and disease, the relationship between fatty acids (FAs) and frailty and mortality remains unclear. The aim of this study was to explore how FA intake is associated with frailty and mortality. Methods: This observational study included 4062 participants 50 y of age from the 2003 2006 cohorts of the National Health and Nutrition Examination Survey. A 36-item frailty index (FI) and a 14-item nutrition index (NI) were constructed. We analyzed 29 dietary FA variables. Results: After adjustment for potential covariates and the NI, higher total FAs, saturated FAs (SFAs), and butanoic acid intake were associated with a higher degree of frailty. After an additional adjustment for the FI, higher SFA intake (total, hexanoic acid, octanoic acid, decanoic acid, tetradecanoic acid, hexadecanoic acid, and octadecanoic acid) was associated with higher mortality risk, whereas higher polyunsaturated FAs (total and octadecadienoic acid), v-3 FAs (total, octadecatrienoic acid, and docosapentaenoic acid), and eicosenoic acid intake was associated with lower mortality risk. Conclusions: Only a higher percentage of SFA intake was associated with both higher frailty and mortality even after considering the degree of nutritional deficits. The effect of SFAs on mortality was evident across levels of frailty. FAs were associated with long-term mortality more often than they with degree of frailty. © 2019 Elsevier Inc. All rights reserved.

Introduction Fatty acids (FAs) play a role in major dietary sources of energy, in cellular respiration as the most calorie-dense macronutrient and in lipid-soluble vitamin absorption. They are involved in the process of cell signaling and gene expression of many metabolic-related proteins and enzymes. Moreover, FAs are important precursors of eicosanoids, which regulate many inflammatory processes [1]. The major dietary lipid components are triacylglycerols (TGs) and free FAs (FFAs), and vary among foods. Dietary FAs are associated with various health conditions including common disorders such as metabolic syndrome, cardiovascular disease, and cancer [2 6]. Even so, their effects on health vary by type and amount [5]. As populations age, fewer people have single illnesses, or even single-system illness. Instead, multiple health deficits accumulate. Deficit accumulation across the life span gives rise to frailty, *Corresponding author: Tel: +1 902 473 4846; Fax: +1 902 473 1050. E-mail address: [email protected] (O. Theou). https://doi.org/10.1016/j.nut.2019.110610 0899-9007/© 2019 Elsevier Inc. All rights reserved.

especially in old age [7,8]. Frailty is a state of increased vulnerability to adverse outcomes among people of the same chronological age [9] and is associated with a higher risk for hospitalization, falls, fracture, disability, and mortality [10,11]. The cause of frailty is complex; multiple interacting factors contribute to this state. Inflammation and oxidative stress, implicated in sarcopenia and cardiovascular diseases, play an important role in frailty [12,13]; higher levels of proinflammatory cytokines are associated with frailty [14] and mortality [15]. However, frailty is potentially a reversible condition that can be improved by a multidisciplinary approach including better nutrition [16]. Given their major role in health and disease and their association with multiple diseases, few studies [17 20] have examined the association between dietary fat and frailty. Most of the studies focused on v-3 FAs and concluded that lower frailty, measured using the frailty phenotype, was associated with the higher intake or supplementation of v-3 FAs. The association between FAs and mortality risk is controversial inasmuch as the results are contradictory (e.g., varying degrees of risk or even benefit attributed to

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saturated FAs [SFAs] [3,21] and polyunsaturated FAs [PUFAs]) [22 24]. The present study aimed to explore the association between FAs and frailty and evaluate the effect of FAs on mortality after controlling for frailty. Material and methods Study population and design This observational study used data from 4724 individuals 50 y of age from the 2003 2006 cohorts of the National Health and Nutrition Examination Survey (NHANES). NHANES is a series of publicly available, cross-sectional surveys focusing on the health and nutrition of non-institutionalized U.S. residents [25,26]. As spelled out in recent reports [27 29], 483 individuals with missing frailty index (FI) scores (99.6% due to blood tests) and 179 with missing information on FA intake were excluded. The final sample included 4062 participants. Each participant signed written informed consent. The NHANES protocol was approved by the institutional review board of the Centers for Disease Control and Prevention (CDC). As a matter of policy, our local Research Ethics Committee does not review secondary analyses of duly approved, publicly available data.

(OLS) regression analysis and presented b-coefficients with corresponding 95% confidence intervals (CIs). The mortality risk for each FA was analyzed using Cox regression models, presented with the hazard ratios (HRs) and the associated 95% CIs. Both linear and non-linear (squared and cubic) associations were examined. The interactions of age and sex with FA variables, in relation to frailty and mortality risk, were also tested in the OLS and Cox regression models. Estimated survival probability of individuals with 5% increase of SFA intake was illustrated in cumulative survival curve. All regression models were adjusted for potential covariates including age (years), sex (male and female), race (non-Hispanic white, non-Hispanic black, Hispanic, and others), education levels (less than high school, high school, some college/associated education, and college graduate or more), marital status (married, widowed, divorced/separated, and never married), employment status (working and non-working), smoking (never, former, and current), study cohort (number), body mass index (BMI; <18.5, 18.5 24.9, 25 29.9, and 30 kg/ m2), energy intake (continuous in kcal), and percent FA intake. These were considered the basic covariates for the analysis. Additionally, the OLS regression analyses were adjusted for NI (continuous score) and the Cox regression analyses were adjusted for NI (continuous score) and FI (continuous score). Annual household income was not included as a covariate owing to missing data (6.3%). Statistical significance was considered as P < 0.05 and all reported probability tests were two-tailed. The statistical analysis was conducted using SPSS version 24 (IBM, Armonk, NY, USA).

Fatty acids data NHANES includes a dietary interview component called What We Eat in America (WWEIA). WWEIA estimates the type and amount of foods and beverages participants consumed 24 h before the interview. This information was used to estimate intakes of energy, nutrients, and other food components. NHANES used U.S. Department of Agriculture's Food and Nutrient Database for Dietary Studies 2.0 and 3.0 to code individual foods and portion sizes reported by participants to calculate the dietary intakes. The NHANES database included 23 FAs and using these FAs, we also calculated 6 additional FAs (v-3 FAs, medium-chained TG, and total FAs, SFAs, monounsaturated FAs [MUFAs] and PUFAs in percentage). The 29 FAs examined were derived from foods alone; no dietary supplements were included. The percentages of total FAs, SFAs, MUFAs, and PUFAs were calculated by the daily amount of intake in grams multiplied by 9 and divided by the daily total energy intake in kilocalories (kcal). Medium-chain FAs were composed of 6 to 12 carbon atoms FAs: hexanoic acid (caproic, 6:0), octanoic acid (caprylic, 8:0), decanoic acid (capric, 10:0), and dodecanoic acid (lauric, 12:0). v-3 FAs included all FAs in the v-3 series: octadecatrienoic acid (a-linolenic acid, 18:3 v-3), octadecatetraenoic acid (stearidonic, 18:4 v-3), eicosapentaenoic acid (EPA, 20:5 v-3), docosapentaenoic acid (DPA, 22:5 v-3), and docosahexaenoic acid (DHA, 22:6 v-3). Nutrition index The NI was based on the accumulation of nutrition-related deficits, previously constructed using 41 parameters including 18 nutrients, 4 anthropometric measurements, and 19 nutrition-related blood tests in the 2003 2006 NHANES cohorts [28,29]. For the purpose of the present study, we constructed the NI only including nutrients. We excluded four nutrient items (energy intake, energy per weight, percentage of SFAs, and fish oil [EPA + DHA]) from the NI. SFAs, EPA, and DHA were used as independent variables in our analysis and energy intake was included as a covariate. Therefore, the NI used here included 14 items (Appendix Table 1). The NI score counts the number of nutritional deficits in an individual in relation to the total deficits considered. A higher score represents overall worse nutritional intake. Outcome assessment: Frailty index and mortality status An FI was used to estimate the overall health state of the participants. We used a 36-item FI that was modified from a validated FI in NHANES [28]. As before, the modification was to exclude from the FI all items related to dietary intake or nutritional status (i.e., difficulty using fork and knife, difficulty preparing meals, glycohemoglobin, TG, creatinine, hemoglobin, mean corpuscular volume, total cholesterol, glucose, and sodium) [28,29]. The FI score was calculated as the number of deficits present divided by the total deficits considered. In theory, FI scores therefore could range between 0 and 1 [30]. Mortality status was identified from the death certificate records from the National Death Index up to December 31, 2015 and survival time was counted from the date of the clinical examination to the death event [31]. Statistical analysis Demographic characteristics of the participants were presented as mean § SD or median (interquartile range [IQR]) for continuous variables and as frequency (%) for binary or categorical variables. All percentages, mean, and median values were weighted using the sampling weights provided by NHANES. The association of baseline demographic data with frailty and mortality was tested using univariate linear regression analysis and Cox regression analysis, respectively. We assessed the association between each FA and FI, using ordinary least squares

Results This study comprised 4062 participants, of whom 53.8% were women. The weighted mean age was 63.6 § 10.3 y, ranging between 50 and 85 y and 39.3% >65 y of age. The mean energy intake was 1936.1 § 819.5 kcal/d. Participants consuming higher percent FAs had lower age and higher total energy intake and BMI (P < 0.001; Table 1). Being older, female, widowed, or a former smoker and having BMI 30 kg/m2, higher NI score, and lower education and energy intake were significantly associated with higher frailty and mortality (P <0.001; Appendix Table 2). The characteristics of the 29 FA variables that we examined are presented in Table 2. The mortality rate was 23.8% or 35.2 cases per 1000 person-years. We did not find any significant interactions between age or sex and the FA variables in relation to frailty. Frailty was significantly associated with higher percent SFA intake (linear relationship; P = 0.024), percent total FAs (P = 0.031), and butanoic acid (butyric, 4:0) intake (nonlinear relationship; P = 0.031) after controlling for the basic covariates and NI. The models accounted for 24% of the variance in FI prediction by percent SFAs, percent FAs, and butanoic acids (Fig. 1 and Appendix Table 3). Regression models were adjusted for basic covariates (sex, race, educational level, marital status, employment status, smoking, energy intake, BMI, percent FA intake, and study cohort) and NI. The predictive value with 95% CI of FA variables significantly associated with frailty are presented in Figure 1 (for results of all FA variables, please see Supplementary Table 2). In relation to mortality, we did not find any significant interactions between age, sex, or FI and the FA variables. After controlling for the basic covariates, NI and FI, higher intake in amount of total SFAs (P = 0.003), hexanoic acid (P = 0.008), octanoic acid (P = 0.019), decanoic acid (P = 0.027), tetradecanoic acid (myristic, 14:0; P = 0.008), hexadecenoic acid (palmitic, 16:0; P = 0.005), and octadecanoic acid (stearic, 18:0; P < 0.001), and in percentage of SFAs (P = 0.001) was significantly associated with higher mortality, whereas higher intake of total PUFAs (P < 0.001) and octadecadienoic acid (linoleic, 18:2 v-6; P < 0.001), total v-3 FAs (P = 0.001), octadecatrienoic acid (P = 0.002), DPA (P = 0.017), and eicosenoic acid (gondoic, 20:1 v-9; P = 0.037), and in percentage of PUFAs (P < 0.001) was associated with lower mortality risk (Fig. 2). Cox regression models were adjusted for basic covariates (sex, race, educational level, marital status, employment status, smoking, energy intake, BMI, percent FA intake, and study cohort), NI

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Table 1 Descriptive characteristics of participants by fatty acid intake Characteristics

Percentage total fatty acid intake per energy All N = 4062

Age, y Sex, female, n (%) Race, n (%) Non-Hispanic white Non-Hispanic black Hispanic Others Education, n (%) Less than high school High school Some college/Associated education College graduate or more Annual household income, USD, n (%) 0 $19 999 $20 000 $44 999 $45 000 $74 999 $75 000 Marital status, n (%) Married Widowed Divorced/Separated Never married Employed full-time, n (%) Smoking status, n (%) Never Former Current Body mass index, kg/m2 Energy intake, kcal/d Frailty index score Nutrition index score

Q1 (2.5% 27.9%) n = 1015

Q2 (28% 33.7%) n = 1016

Q3 (33.8% 39.5%) n = 1016

Q4 (39.6% 69.4%) n = 1015

63.6 § 10.3 2031 (53.8)

64.1 § 10.7 517 (54.5)

64.5 § 10.6 531 (57.4)

63.6 § 10.5 505 (53.1)

62.4 § 9.5 478 (50.5)

2431 (80.4) 748 (9.1) 756 (6.3) 127 (4.2)

557 (76.3) 184 (9.7) 230 (8.6) 44 (5.4)

622 (80.4) 180 (8.8) 179 (6.2) 35 (4.7)

606 (79.9) 198 (9.6) 184 (6.3) 28 (4.2)

646 (84.4) 186 (8.4) 163 (4.4) 20 (2.8)

1351 (20.1) 1005 (27.6) 974 (28.4) 726 (23.9)

379 (22.8) 212 (23.6) 227 (27.5) 196 (26.1)

332 (21.2) 256 (28.7) 241 (26.7) 184 (23.4)

338 (19.6) 261 (27.3) 244 (28.6) 173 (24.5)

302 (17.4) 276 (30.1) 262 (30.5) 173 (22)

1080 (18.9) 1325 (32.4) 739 (24.1) 663 (24.6)

286 (21.4) 325 (31) 162 (21.1) 167 (26.4)

261 (18.4) 345 (35) 187 (23.4) 160 (23.2)

281 (18.8) 327 (31.3) 192 (24.7) 168 (25.3)

252 (17.2) 328 (32.3) 198 (26.7) 168 (23.8)

2452 (66) 816 (15.1) 607 (14.8) 184 (4.1) 1385 (54.4)

599 (62.8) 207 (16.6) 155 (14.8) 54 (5.7) 313 (54.3)

607 (66) 227 (16.8) 134 (13.4) 46 (3.9) 346 (59.3)

613 (66.6) 206 (14.7) 157 (15.4) 40 (3.3) 395 (53.4)

633 (68.2) 176 (12.8) 161 (15.5) 44 (3.5) 313 (50.7)

1850 (46.1) 1553 (36.9) 659 (17) 28.8 § 6.2 1936.1 § 819.5 0.16 § 0.12 0.37 § 0.26

479 (46.3) 367 (36.4) 169 (17.3) 28.2 § 6 1683.9 § 780.1 0.17 § 0.12 0.40 § 0.29

500 (50.5) 382 (35.7) 134 (13.8) 28.3 § 5.8 1896 § 761.6 0.17 § 0.12 0.35 § 0.29

467 (47.5) 382 (35.2) 167 (17.3) 28.9 § 6.1 2029.6 § 880.3 0.16 § 0.12 0.36 § 0.25

404 (40.5) 422 (40.0) 189 (19.4) 29.6 § 6.6 2101.3 § 791 0.16 § 0.12 0.37 § 0.23

Q, quartile; USD, US dollar. Percentages and mean values are weighted. All values mean § SD unless otherwise noted.

and FI. Only FAs significantly associated with mortality risk are presented (for results of all FA variables, see Supplementary Table 3). Higher DHA intake was also associated with lower mortality risk; however, the association did not remain after controlling for FI (Appendix Table 4). SFA intake >20% was significantly associated with increased mortality risk but the overall survival rate, even for this group, was high (Fig. 3). Discussion We examined the association of the intake of FAs individually, and as groups, with frailty and mortality risk after considering for the degree of nutritional deficits. We found that there was an association between frailty and three FA variables (percent total FAs, percent SFAs, and butanoic acid) in middle-age and older individuals. Higher mortality risk was associated with higher intake in eight FA variables and lower intake in seven. Higher consumption in percent SFAs was associated with increased risk in both frailty and mortality. The effect of SFAs on mortality risk was found in the individual long-chain SFAs (tetradecanoic acid, hexadecanoic acid, and octadecanoic acid) and in some individual medium-chain SFAs (hexanoic acid, octanoic acid, and decanoic acid). SFAs influence many genes that regulate lipid metabolism and the inflammatory process [32,33]. Substitution of carbohydrates with SFAs results in dyslipidemia by raising serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) with a small increase in serum high-density lipoprotein cholesterol (HDL-C) [5,34]. High SFA consumption

(especially dodecanoic, tetradecanoic, and hexadecanoic acids) also increases coagulation, inflammation, and insulin resistance. These conditions are associated with higher risk for age-related adverse health outcomes (e.g., type 2 diabetes, cardiovascular diseases, cerebrovascular diseases, and cancer) [1,35] and could link to increased risk for frailty and mortality [12,36]. Here, we found that eisosenoic acid, a MUFA, was associated with lower mortality risk. Nonetheless, neither MUFAs nor other individual MUFAs were significantly associated with risk for frailty or mortality. Evidence from previous studies about the relationship between MUFAs and health outcomes are inconsistent. Substitution of SFAs with octadecenoic acid, the most prevalent dietary MUFA, decreased LDL-C [1] and higher MUFA consumption reduced the risk for all-cause and cardiovascular mortality, and incidents of cardiovascular events and stroke [37]. Additionally, the Mediterranean diet, in which the main lipid component is olive oil, prevented sarcopenia in older adults [38], reduced proinflammatory markers [39], and decreased the incidence of frailty [40] and major cardiovascular events [41]. Nevertheless, high olive oil consumption did not significantly change the levels of small TGrich lipoproteins in individuals with BMI <26.18 kg/m2 [42] and recent studies [43,44] did not show any effect of dietary MUFAs on coronary outcomes in the older population, but they did in the younger group. This study confirmed protective effects of v-3 FAs (total, octadecatrienoic acid, DPA, and DHA) on mortality; however, we did not find a protective relationship of these FAs with frailty. This may be due to v-3 FAs being more associated with long-term

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Table 2 Mean or median of fatty acid intake Mean § SD or median (IQR) Total fatty acids (g) SFAs (g) MUFAs (g) PUFAs (g) Total fatty acids per energy (%) SFAs per energy (%) MUFAs per energy (%) PUFAs per energy (%) Medium-chain fatty acids (g) v-3 fatty acids (g) Butanoic acid (g) Hexanoic acid (g) Octanoic acid (g) Decanoic acid (g) Dodecanoic acid (g) Tetradecanoic acid (g) Hexadecanoic acid (g) Octadecanoic acid (g) Hexadecenoic acid (g) Octadecenoic acid (g) Eicosenoic acid (g) Docosenoic acid (mg) Octadecadienoic acid (g) Octadecatrienoic acid (g) Octadecatetraenoic acid (mg)* Eicosatetraenoic acid (mg)* Eicosapentaenoic acid (mg)* Docosapentaenoic acid (mg)* Docosahexaenoic acid (mg)*

75.65 § 40.68 24.77 § 14.64 28.01 § 16.06 16.44 § 10.87 34.40 § 9.08 11.29 § 4.10 12.67 § 3.91 7.48 § 3.35 1.12 (0.52 2.24) 1.30 (0.80 2.02) 0.38 (0.14 0.75) 0.19 (0.08 0.40) 0.16 (0.07 0.31) 0.30 (0.14 0.58) 0.41 (0.19 0.82) 2.06 § 1.72 13.36 § 7.51 6.40 § 3.76 0.97 (0.59 1.52) 23.26 (15.39 33.65) 0.17 (0.09 0.29) 6.0 (1 31) 12.24 (7.68 18.35) 1.19 (0.74 1.81) 0 (0 1) 98 (46 174) 5 (0 17) 2 (0 18) 23 (2 61)

MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; SFA, saturated fatty acids. Mean and median values are weighted. *These fatty acids were reported in mg due to small amount of intake.

rather than with short-term health outcomes. v-3 FAs decrease blood TG levels and both EPA and DHA benefit anti-inflammatory action [45], cognitive function [46], and cardiovascular outcomes [47]. Moreover, 6 mo of supplementation with fish oil improves physical performance [20]. Dietary octadecatrienoic acid consumption is associated with lower mortality risk [48]; however, a systematic review revealed no effect of overall v-3 FA intake on mortality [49]. We also revealed an inverse association of total PUFAs and octadecadienoic acid intake with mortality risk. Although octadecadienoic acid is related to proinflammatory processes, which could lead to adverse health outcomes, replacing SFAs with octadecadienoic acid and other PUFAs reduces mortality rates [50,51]. The number of FA variables associated with frailty was less than the number of FA variables associated with mortality risk. FA intake may be associated with long-term health more than with current health status. Frailty status could be influencing FA intake and FA intake could affect the frailty degree of the individuals. Also, the pathologic pathways of FAs to frailty may be different than those on mortality. For example, higher octadecatrienoic acid protects from sudden cardiac death but not from coronary heart disease, and this may support the hypothesis in its anti-arrhymic properties [52]. We did not find an interaction of FAs with frailty on mortality but adjusting for the degree of frailty affected the relationship of some FAs, such as DHA, with mortality. This suggests that frailty may be a mediator and not a moderator of the relationship between FAs and mortality and that the degree of frailty should be considered when examining the relationship of FAs intake with health outcomes. Future studies should examine the relationship between dietary FAintake and metabolic diseases such as diabetes and obesity. Using the NHANES data included

Fig. 1. Relationship between fatty acid intake and frailty.

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Fig. 2. Relationship between fatty acid intake and mortality risk.

Fig. 3. Relationship between saturated fatty acid intake and mortality risk.

here, we found that higher total FA intake was associated with fasting blood glucose 126 mg/dL, BMI 30 kg/m2, and abnormal WC (male 94 cm and female 80 cm); lower v-3 FA intake was also associated with abnormal WC (data not shown).

The present study analyzed the publicly available NHANES data, a large population-based study with a well-controlled and rigorous protocol. Mortality was extracted from death certificate data and had a long follow-up period after testing. All dietary FAs were

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evaluated by controlling various potential factors including overall health and nutrition status. Because foods include more than one nutrient and avoiding a food or nutrient leads to an increase in other foods or nutrients (or vice versa), the analyses were controlled for total energy intake, percentage of total FA intake, and nutritional deficits. Nevertheless, this data must be interpreted with caution:  Due to the cross-sectional design, the causal relationship between frailty and nutrition could not be examined and the duration of exposure to each parameter could not be explored.  As dietary data were recorded by 24-h recall, day-to-day variation could not be counted, and food intake could be altered along the study period.  The estimates relied on self-reported dietary data that did not include supplement use.  People change their diet when they start to feel unwell, so reverse causation is possible. For example, total SFA intake was 25.64 § 15.32 g/d in individuals having FI  0.1 and 20.40 § 11.81 g/d in individuals having FI > 0.3. Future studies using longitudinal data should investigate the interaction between FAs and other nutrients and their combined effects on health. Future studies should also investigate whether dietary interventions should target specific nutrients such SFAs or focus on improving diet as a whole to have an effect on frailty. Conclusions The present study revealed that the intake of three FAs was associated with frailty but more than half of FAs were associated with mortality risk. The percentage of SFAs was the only FA that was associated with increased risk in both frailty and mortality. Higher consumption of PUFAs and v-3 FAs was associated with lower mortality risk. FA intake may be associated with long-term health to a greater degree than they were with current health status and the pathologic pathways of FAs to frailty may be different than those of FAs to mortality. Frailty should be considered when examining the relationship of FAs intake with health outcomes. Acknowledgments The authors acknowledge the Faculty of Medicine Ramathibodi Hospital, Mahidol University for supporting KJ with a research fellowship to conduct this research and our colleagues in Geriatric Medicine Research, at Dalhousie University & Nova Scotia Health Authority for their support. Supplementary materials Supplementary material associated with this article can be found in the online version at doi:10.1016/j.nut.2019.110610. References [1] Calder PC. Functional roles of fatty acids and their effects on human health. JPEN J Parenter Enteral Nutr 2015;39(1 suppl):18S–32S. [2] Maximino P, Horta PM, dos Santos LC, de Oliveira CL, Fisberg M. Fatty acid intake and metabolic syndrome among overweight and obese women. Rev Bras Epidemiol 2015;18:930–42. [3] de Souza RJ, Mente A, Maroleanu A, Cozma AI, Ha V, Kishibe T, 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;351:h3978.

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