western diet and fatty liver

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The American Journal of GASTROENTEROLOGY VOLUME 108 | MAY 2013 www.amjgastro.com

INTRODUCTIONNonalcoholic atty liver disease (NAFLD) is pathogenically asso-ciated with obesity and insulin resistance and has been identi-

ed as a predictor o cardiovascular disease and type 2 diabetesmellitus in adults and children (1). As the prevalence o obes-ity and diabetes has increased worldwide over the past twodecades, NAFLD is now the leading cause o liver injury (1).NAFLD may progress to cirrhosis, risking complications o

hepatocellular carcinoma and liver ailure, and is becoming aincreasingly common indication or liver transplant (2). Tepediatric and adolescent age group has not been immune to theglobal overweight and obesity epidemic, with the prevalence oNAFLD ranging between 3 and 13% in these populations (1,3),and NAFLD affects up to 52% o overweight and obese children(4). Tese children are potentially at a li e-long risk o developinNAFLD-related complications.

The Western Dietary Pattern Is Prospectively Associated

With Nonalcoholic Fatty Liver Disease in AdolescenceWendy H. Oddy , BAppSci, MPH, PhD 1 , Carly E. Herbison , BSc (Hons) 1 , Peter Jacoby , BA, MSc1 , Gina L. Ambrosini , BAppSci, MPH, PhD 2 ,Therese A. O Sullivan, BHlthSci, BAppSci, PhD 1 , 3 , Oyekoya T. Ayonrinde , MBBS, FRACP 4 6 , John K. Olynyk , MBBS, FRACP, MD 4 7 ,Lucinda J. Black , BSc, PhD 1 , Lawrence J. Beilin , MBBS, FRCP, FRACP, FCSANZ, MD 4 , Trevor A. Mori, BSc (Hons), MRACI CChem,PhD (Distinction) 4 , Beth P. Hands , BEd, BSocWk, MEd, PhD 8 and Leon A. Adams , MBBS, FRACP, PhD 4

OBJECTIVES: Poor dietary habits have been implicated in the development of nonalcoholic fatty liver disease(NAFLD); however, little is known about the role of specic dietary patterns in the developmentof NAFLD. We examined prospective associations between dietary patterns and NAFLD in apopulation-based cohort of adolescents.

METHODS: Participants in the Western Australian Pregnancy Cohort (Raine) Study completed a food frequencyquestionnaire at 14 years and had liver ultrasound at 17 years ( n = 995). Healthy and Western dietarypatterns were identied using factor analysis and all participants received a z -score for thesepatterns. Prospective associations between the dietary pattern scores and risk of NAFLD wereanalyzed using multiple logistic regression.

RESULTS: NAFLD was present in 15.2 % of adolescents. A higher Western dietary pattern score at 14 years wasassociated with a greater risk of NAFLD at 17 years (odds ratio (OR) 1.59; 95 % condence interval(CI) 1.17 2.14; P < 0.005), although these associations were no longer signicant after adjustingfor body mass index at 14 years. However, a healthy dietary pattern at 14 years appeared protectiveagainst NAFLD at 17 years in centrally obese adolescents (OR 0.63; 95 % CI 0.41 0.96; P = 0.033),whereas a Western dietary pattern was associated with an increased risk of NAFLD.

CONCLUSIONS: A Western dietary pattern at 14 years in a general population sample was associated with anincreased risk of NAFLD at 17 years, particularly in obese adolescents. In centrally obeseadolescents with NAFLD, a healthy dietary pattern may be protective, whereas a Western dietarypattern may increase the risk.

SUPPLEMENTARY MATERIAL is linked to the online version of the paper at http://www.nature.com/ajg

Am J Gastroenterol 2013; 108:778785; doi:10.1038/ajg.2013.95; published online 2 April 2013

1 Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia , Perth , Western Australia , Australia ; 2 MedicalResearch Council Human Nutrition Research , Cambridge , UK; 3 School of Exercise and Health Sciences, Edith Cowan University , Joondalup , Western Australia ,Australia; 4 School of Medicine and Pharmacology, The University of Western Australia , Perth , Western Australia , Australia ; 5 Department of Gastroenterology,Fremantle Hospital , Fremantle , Western Australia , Australia ; 6 Curtin Health Innovation Research Institute, Curtin University of Technology , Perth , WesternAustralia, Australia ; 7 Institute for Immunology and Infectious Diseases, Murdoch University , Perth , Western Australia , Australia ; 8 School of Health Sciences,University of Notre Dame , Fremantle , Western Australia , Australia . Correspondence: Wendy H. Oddy, BAppSci, MPH, PhD , Telethon Institute for Child HealthResearch , PO Box 855 West Perth , WA 6872 , Australia . E-mail: [email protected] 19 October 2012; accepted 10 March 2013


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The Western Dietary Pattern and Fatty Liver Disease

Te pathogenesis o NAFLD and obesity is traditionally thoughtto be due to excess caloric intake in association with reduced energyexpenditure (5); however, there is a paucity o evidence examiningspeci c dietary habits and the development o NAFLD. Althoughexcess adiposity is a major risk actor or NAFLD, it is not knownwhether speci c dietary patterns predispose to NAFLD independ-ently o excessive adiposity. Conversely, as not all overweight individuals will develop NAFLD, it is unknown whether speci c dietarypatterns may protect against the development o NAFLD in normalor overweight groups. Diet consists o complex combinations o

oods and nutrients ingested together that may act independentlyor interact in a complimentary, synergistic, or antagonistic man-ner. Dietary pattern analysis examines the overall effect o diet (6),allowing quanti cation o the cumulative effect o multiple oodsand nutrients and avoids issues o con ounding and colinearity.

Tere are a number o studies reporting a prospective associa-tion between dietary patterns, adiposity, and the metabolic syn-drome in children (710); however, the evidence relating dietary

patterns to NAFLD is limited. o our knowledge, an associationbetween dietary patterns and NAFLD has not been reported,although a higher intake o sof drinks and meatthe main com-ponents o a Western dietary patternhas previously been associ-ated with NAFLD in adults (11). We investigated the prospectiverelationship between dietary patterns at age 14 years with NAFLDat 17 years in adolescents participating in the Western AustralianPregnancy Cohort (Raine) Study.

METHODSStudy population

Te Western Australian Pregnancy Cohort (Raine) Study is aprospective longitudinal study, the details o which have beenpublished previously (12). In brie , 2,900 pregnant women wererecruited through the public antenatal clinic and local privateclinics in Perth, Western Australia between 1989 and 1991. A totalo 2,804 women (97%) had 2,868 live births, and these childrenhave undergone serial assessment at birth and at ages 1, 2, 3, 5,8, 10, 14, and 17 years. All data collection or the Raine Studyoccurred in accordance with the Australian National Healthand Medical Research Council Guidelines or Ethical Conductin Human Research and was approved by the ethics commit-tees o King Edward Memorial Hospital or Women and PrincessMargaret Hospital or Children, Perth, Western Australia.In ormed consent was obtained in writing rom the adolescentand their primary caregiver.

Dietary patterns assessment at age 14 yearsIdenti cation o the Western and healthy dietary patterns in thiscohort at age 14 years has previously been described (13) andevaluated (14). An evaluated semiquantitative ood requencyquestionnaire (FFQ) (15) was mailed to the primary caregivers othe study adolescents to complete with the adolescent. Te FFQprovided usual requency o consumption and serving size in or-mation on 212 oods or dishes, which were collapsed into 38 oodgroups that were de neda priori (13). Foods with a actor loading

greater than an absolute value o 0.30 were considered importantcomponents o each pattern.

Te healthy and Western dietary patterns differed predomi-nantly in at and sugar intakes and explained 84% o the total variance in ood intakes (13). Te healthy pattern was positivelycorrelated with whole grains, ruit, vegetables, legumes, sh, ber

olic acid, and most micronutrients, and was inversely correlatedwith energy rom total at, saturated at, and re ned sugar (13). TeWestern pattern was characterized by high intakes o take-away

oods, red meats, processed meats, ull- at dairy products, riepotatoes (hot chips or French ries), re ned cereals, cakes andbiscuits, con ectionery, sof drinks, crisps, sauces, and dressings.Tis pattern was positively correlated with most micronutrientsexcept vitamin C and olic acid. Each subject received az -score oreach pattern, indicating how closely their reported dietary intakecorresponded with the two patterns.

Dietary misreporting is a common source o measurement errorthat can obscure dietdisease relationships (16). Dietary misre-

porting was estimated using the Goldberg method (17), whichestimates the cutoff levels or plausible reporting based on energyintake relative to basal metabolic rate and is an established methodto identi y the level o misreporting rom dietary surveys (18,19).Tese cutoffs were used to classi y respondents as likely underre-porters, plausible reporters, or overreporters. As dietary under-reporting is strongly associated with the risk o overweight (20),excluding underreporters would have removed those participantsat greatest risk. Tere ore, a categorical variable or misreportingwas included as a covariate in the logistic regression models.

Liver ultrasonography at age 17 years

Liver ultrasonography was conducted at the 17-year ollow-up.rained ultrasonographers per ormed liver ultrasound using aSiemens Antares ultrasound machine, with a CH 6-2 curved arrayprobe (Sequoia, Siemens Medical Solutions, Mountain View, CA)according to the protocol described by Hamaguchiet al. (21) thatprovides 92% sensitivity and 100% speci city or the histologicaldiagnosis o atty liver. A single specialist radiologist, blinded tthe clinical and laboratory characteristics o the subjects, inter-preted the ultrasound images. Scores o 03, 02, and 01 weredetermined rom captured images or liver echotexture (brightliver and hepatorenal echo contrast), deep attenuation (dia-phragm visibility), and vessel blurring (intrahepatic vessel visibil-ity), respectively. Te diagnosis o FLD required a total score o atleast 2, including echotexture score o at least 1.

In ormation on alcohol intake over the past 12 months wasobtained rom the FFQ and li estyle questionnaire. Adolescentswith sonographic atty liver and a sel -reported weekly alcohointake o < 210 and 140 g or males and emales, respectively, weclassi ed as having NAFLD (22). Medications and a comprehen-sive medical history were documented to exclude secondary causeso NAFLD and concomitant liver disease.

Biochemistry at age 17 yearsVenous blood samples were taken afer an overnight ast. Results

rom non asting samples were excluded rom this analysis. Serum


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insulin, glucose, triglycerides, high-density lipoprotein cholesterol,alanine transaminase, -glutamyltrans erase, and high-sensitivityC-reactive protein were measured as previously described (23).Homeostasis model assessment or insulin resistance (HOMA-IR),as a measure o insulin resistance, was calculated by insulin ((mU/ l)glucose (mmol/l)/22.5) (24).

AnthropometryHeight, weight, and waist circum erence were measured bytrained assessors using standardized methods at 14 and 17 years.Body mass index (BMI: weight (kg)/height (m)2 ) was calculatedand subjects were grouped into underweight, normal weight,overweight, and obese categories using International Obesity askForce (IO F) criteria at 14 years (25,26). Waist circum erence wasmeasured as the mid-point between the iliac crest and the lowercostal margin by horizontally positioning a tape measure acrossthe belly button and at the smallest girth at the back, taking theaverage o two measurements. Central obesity was de ned as

waist circum erence 80 cm in emales and 94 cm in males, consist-ent with International Diabetes Federation (IDF) criteria (27).

Family incomePrimary caregivers were asked to report their gross amily incomeper year at the 14-year ollow-up (20032006). Eleven categorieso income (in Australian dollars) were collapsed into our catego-ries ($30,000 p.a., $30,001$50,000 p.a., $50,001$78,000 p.a., and>$78,000 p.a.).

Physical activity and sedentary behaviorAt the 14-year ollow-up, hours o physical activity per week and

time spent watching television were assessed using a sel -reportedwritten questionnaire. Participants detailed the time spent exer-cising vigorously during physical education at school, and howofen and or how long they got out o breath or perspired whileexercising outside school hours.

Statistical methodsTe 2 tests were used to compare the characteristics o study par-ticipants at 14 years, including sex, amily income, BMI status,dietary misreporting, physical activity per week, and sedentarybehavior (television viewing) according to NAFLD status at17 years. Independent samplest -tests were used to comparemean values or biochemistry and central adiposity according toNAFLD status at 17 years. Te odds o NAFLD were analyzed inrelation toz -scores or both dietary patterns using logistic regres-sion. Furthermore, dietary pattern scores were analyzed in quar-tiles based on the total sample distribution. Associations betweenthe dietary pattern as a continuous score and in quartiles are pre-sented or three different models. Te rst model included scores

or both healthy and Western dietary patterns, sex, and dietarymisreporting. A second model additionally adjusted or amilyincome, requency, and intensity o physical activity and sedentarybehavior at 14 years. Te third model adjusted or adolescent BMIat 14 years. A subgroup o adolescents with central obesitywas examined in logistical regression models, adjusting or

dietary patterns, sex, dietary misreporting, physical activity, antelevision viewing.

o urther explore any associations between the dietary patternand NAFLD, intakes o key ood groups in each pattern, i.e., thhaving a actor loading o 0.30 (13), were examined in relation toNAFLD risk. Tese were converted into quartiles and entered intoseparate logistic models adjusting or covariates, as per the moddescribed above. In addition, the healthy and Western dietary pat-tern scores were retained in the models to test i ood group assciations were independent o the overall dietary patterns.

Initial exploratory analyses in the continuous models also testethe importance o aerobic tness (watts) and alcohol intake a14 years o age as con ounders. However, these did not improthe model or alter the associations between dietary patterns andNAFLD risk and were, there ore, not retained in nal models. Adata analyses were conducted using IBM SPSS Statistics ReleaVersion 19.0.0.1 (IBM SPSS, 2010, Chicago, IL).

RESULTSStudy participant characteristicsAt the 14-year ollow-up, there were 2,337 adolescents eligib(alive and not withdrawn rom the study) and at 17 years, 2,16adolescents were eligible to participate. A total o 1,857 (79.5% otraced) adolescents responded to the 14-year ollow-up, o who1,613 had complete plausible data rom the FFQ (because o higimplausible energy intakes ( < 3,000 kJ/day or >20,000 kJ/day) 18respondents were excluded rom analysis). At age 17 years 1,1adolescents underwent hepatic ultrasound. Complete data wereavailable or 995 adolescents who provided dietary in ormati

and had ultrasound assessment or NAFLD. O the 995 study pticipants with complete data, NAFLD was present in 151 (15.2%)at age 17 years (Table 1 ). O those with NAFLD at age 17 year54.1% were overweight or obese at age 14 years.

Biochemistry and anthropometry prole at 17 yearsTe serum biochemistry and anthropometry pro les o study par-ticipants at 17 years are shown in order to characterize NAFLDin the cohort (Table 2 ). Subjects with NAFLD had higher insu-lin resistance (HOMA-IR), raised triglycerides and reducedhigh-density lipoprotein cholesterol, elevated alanine transaminase, -glutamyltrans erase, and high-sensitivity C-reactive protein, as well as greater adiposity (BMI, waist circum erence, awaist-to-hip ratio).

Dietary patterns and NAFLDAssociations between the dietary pattern scores at 14 years anNAFLD at 17 years are shown inTable 3 . In the total population,the healthy dietary pattern did not show any associations withthe odds o NAFLD, either as a continuous outcome (model odds ratio (OR) 1.15; 95% con dence interval (CI) 0.921.44;P = 0.212) or as quartiles. However, a higher score or the Westedietary pattern was positively associated with the odds o NAFLat 17 years (model 2: OR 1.59; 95% CI 1.172.14; P = 0.003).Tere was a signi cant association between increasing quartiles


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o Western dietary pattern scores and the odds o NAFLD (P ortrend = 0.030). Tose in the highest quartile or the Western die-tary pattern had a 2.6 times greater odds o NAFLD (OR 2.64;95% CI 1.345.18;P = 0.005) compared with those in the lowestquartile (model 2). However, afer adjustment or BMI at age 14years (model 3), these associations were attenuated and no longerstatistically signi cant, indicating that the association between theWestern dietary pattern and NAFLD is likely acting through anobesity pathway. Tese associations did not change i waist cir-cum erence or abdominal skin old was applied instead o BMI.Te same result was ound when BMI at 17 years was includedin the model (data not shown).Figure 1 shows the associationbetween Western dietary pattern and the risk o NAFLD strati-

ed by sex. Tere was a signi cant interaction between sex andthe Western dietary pattern scores (P = 0.008) but not or the

healthy dietary pattern, nor when BMI was included in the model(P = 0.079).

In a subgroup o adolescents with central obesity at age 17 years(n = 191), a healthy dietary pattern was signi cantly associatedwith a reduced risk o NAFLD (OR 0.63; 95% CI 0.410.96;P = 0.033). Tere was a strong trend toward the Western dietarypattern increasing the risk o NAFLD in this subgroup (OR 1.53;95% CI 0.942.50;P = 0.090).

Components of the Western dietary patternAs the Western dietary pattern was signi cantly associated withthe risk o NAFLD ollowing adjustment or covariates,Table 4 illustrates the Western dietary pattern and main ood componentsthat make up the pattern, including the mean and median intakesin grams per day as well as the interquartile range o intake o

Table 1 . Characteristics of participants at 14 years and nonalcoholic fatty liver disease (NAFLD) at 17 years

NAFLD, n (row % )

P value a Total, n No Yes

995 844 (84.8) 151 (15.2)

Characteristics at 14 years Sex n (column % ) < 0.001

Female 496 400 (47.4) 96 (63.6)

Male 499 444 (52.6) 55 (36.4)

Family income 979 0.092

$30,000 per year 131 (15.8) 34 (22.8)

$30,001 $50,000 per year 164 (19.8) 34 (22.8)

$50,001 $78,000 per year 235 (28.3) 34 (22.8)

> $ 78,000 per year 300 (36.1) 47 (31.5)

Misreporting 963 < 0.001

Underreporting 307 (37.6) 88 (60.3)Plausible reporting 450 (55.1) 53 (36.3)

Overreporting 60 (7.3) 5 (3.4)

Physical activity 958 0.020

4 + times per week 288 (35.4 ) 35 (24.1)

13 times per week 447 (54.9) 97 (66.9)

1 time per month or less 79 (9.7) 13 (9.0)

TV viewing per day 958 0.026

< 2 h per day 430 (52.9) 59 (40.7)

24 h per day 277 (34.1) 62 (42.8)

> 4 h per day 106 (13.0) 24 (16.6)Body mass index 961 < 0.001

Underweight 55 (6.7) 5 (3.4)

Healthy weight 610 (74.8) 62 (42.5)

Overweight 123 (15.1) 48 (32.9)

Obese 27 (3.3) 31 (21.2)

a The 2 test.



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these components. Adolescents in the top quartile or sof drinkand sauces/dressings consumption had twice the odds o NAFLDTe sex-speci c results o Table 4 are provided inSupplementaryTables S1 and S2 online .

In multilinear models, the Western dietary pattern was a signicant risk or BMI at 14 years ( 1.41; 95% CI 1.121.82;P < 0.0005),abdominal skin old at 17 years ( 2.14; 95% CI 1.263.03;P < 0.0005), and being in the top 25% o BMI categories at 17 year(OR: 2.17; 95% CI 1.652.85;P < 0.0005).

DISCUSSIONA Western dietary pattern characterized by a high intake o takeaway oods, con ectionary, red meat, re ned grains, processmeats, chips, sauces, ull- at dairy products, and sof drinks wprospectively associated with NAFLD independent o sex, dietamisreporting, amily income, requency o physical activity, sedentary behavior. In particular, high intakes o sof drinks

sauces, and dressings were associated with an increased risk oNAFLD. Te association between the Western dietary pattern andNAFLD was not independent o BMI, suggesting that this ditary pattern acts predominantly on NAFLD via obesity. Indeedother studies have linked similar dietary patterns with obesityin adolescents (28,29). Although we did not observe any protec-tive relationship between the healthy dietary pattern and NAFLDin the total cohort, in those emales and males who had waicircum erences >80 and 94 cm, respectively, the healthy dieta

Table 2 . Biochemistry and adiposity prole at age 17 years

NAFLD

No Yes

Mean (s.d.) P value a

Biochemistry ( n=827) b

HOMA-IR 1.8 (1.6) 3.1 (5.4) < 0.001

Triglycerides (mmol /l) 1.0 (0.5) 1.2 (0.6) 0.003

Cholesterol (mmol /l) 4.1 (0.7) 4.2 (0.9) 0.248

LDL-C (mmol /l) 2.3 (0.6) 2.4 (0.8) 0.095

HDL-C (mmol /l) 1.3 (0.3) 1.2 (0.3) < 0.001

ALT (U /l) 20.3 (10.4) 27.4 (21.4) < 0.001

GGT (U /l) 14.2 (7.4) 17.3 (11.6) < 0.001

hsCRP (mg /l) 1.5 (5.2) 2.8 (4.6) 0.010

Adiposity ( n=994)

Body mass index 22.0 (3.2) 27.7 (6.1) < 0.001Waist circumference (cm) 77.3 (8.7) 90.4 (15.8) < 0.001

Waist /hip ratio 0.81 (0.06) 0.85 (0.08) < 0.001

ALT, alanine transaminase; GGT, -glutamyltransferase; HDL-C, high-densitylipoprotein cholesterol; HOMA-IR, homeostasis model assessment for insulinresistance; hsCRP, high-sensitivity C-reactive protein; LDL-C, low-densitylipoprotein cholesterol; NAFLD, nonalcoholic fatty liver disease.a Independent samples t -test.b Fasting blood samples.

Table 3 . Adjusted multiple logistic regression models of dietary patterns and risk of NAFLD

Risk of NAFLD

Model 1 a ( n = 965) Model 2 b ( n = 942) Model 3 c (n = 940)

OR (95 % CI) P value OR (95 % CI) P value OR (95 % CI) P value

Continuous measure

Healthy dietary pattern 1.14 (0.91 1.42) 0.240 1.15 (0.92 1.44) 0.212 1.05 (0.83 1.35) 0.674

Western dietary pattern 1.67 (1.26 2.23) < 0.001 1.59 (1.17 2.14) 0.003 1.12 (0.81 1.55) 0.513

Quartiles

Healthy dietary pattern

Q1 (ref.) 1.00 0.38 1.00 0.441 1.00 0.657

Q2 1.29 (0.78 2.15) 0.318 1.39 (0.83 2.33) 0.83 1.29 (0.74 2.27) 0.371

Q3 1.01 (0.59 1.73) 0.967 1.04 (0.60 1.81) 0.888 0.92 (0.51 1.67) 0.781Q4 1.36 (0.80 2.30) 0.261 1.41 (0.82 2.45) 0.219 1.10 (0.61 1.98) 0.744

Western dietary pattern

Q1 (ref.) 1.00 0.005 1.00 0.030 1.00 0.858

Q2 1.30 (0.80 2.14) 0.293 1.25 (0.76 2.08) 0.380 1.02 (0.60 1.75) 0.931

Q3 2.11 (1.20 3.72) 0.010 1.97 (1.09 3.55) 0.024 1.22 (0.65 2.30) 0.529

Q4 3.12 (1.63 5.97) 0.001 2.64 (1.34 5.18) 0.005 1.32 (0.64 2.72) 0.447

CI, condence interval; NAFLD, nonalcoholic fatty liver disease; OR, odds ratio; Q, quartile.a Adjusted for healthy and western dietary patterns, sex, and misreporting at 14 years.b Adjusted as for model 1 plus family income, TV use (sedentary behavior), and frequency of physical activity at 14 years.c Adjusted as for model 2 plus body mass index (BMI) at 14 years.


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pattern reduced the risk o subsequent NAFLD, whereas the West-ern dietary pattern was associated with the risk o NAFLD at age17 years. As dietary habits are ormed during childhood andretained into adulthood, the Western dietary pattern has a potentialin uence on the perpetuation o NAFLD risk. Tese results sup-port our previous nding in the Raine Study linking the Westerndietary pattern with greater cardiometabolic risk (30). Although

relationships with the dietary patterns were different or malesand emales, both were positively related to NAFLD.

Few studies have looked at the association o dietary patternsand NAFLD. One previous cross-sectional study o Israeli adultsaged 24 to 70 years (n = 375) ound an increased risk o NAFLD inthose with a higher intake o sof drinks, whereas a higher intakeo omega-3-rich oods reduced the risk (11).

A Western diet high in processed sugars and at has been shownto cause deleterious effects in nonobese rats, with such a diet lead-ing to the development o hepatic steatosis (31). We showed thata higher consumption o sof drink was associated with a greaterrisk o NAFLD, and the mechanism behind this may be throughprovision o excess kilojoules and large amounts o sugars suchas ructose (29,32). Te consumption o ructose has been linkedto NAFLD, as well as various aspects o the metabolic syndromeincluding dyslipidemia, visceral adiposity, insulin resistance, andhigh blood pressure (33). Sof drinks may contain large amountso high- ructose corn syrup (55% ructose; 45% glucose), the

consumption o which has increased substantially in the past30 years (34).

Foods common in the Western dietary patternincludingre ned grains, white bread, and con ectionarycause a rapidincrease in postprandial plasma glucose and insulin levels and areassociated with obesity, insulin resistance, and diabetes (36). Suchhigh glycemic index oods cause increased hepatic at storage inanimal studies (37), with a similar association seen in humans,where high dietary glycemic index was associated with increasedhepatic steatosis, particularly in insulin-resistant subjects (38). It is

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Western dietary pattern quartile

O R ( 9 5 %

C I )

Males

Females

Figure 1 . Adjusted * model of Western dietary pattern (in quartiles) andrisk of nonalcoholic fatty liver disease, stratied by sex. * Adjusted forhealthy dietary pattern, misreporting, family income, frequency of physicalactivity, and TV viewing. CI, condence interval; OR, odds ratio.

Table 4 . Quartiles of the western dietary pattern and components of the pattern (g /day) at 14 years and risk of NAFLD at 17 years(n =940) a

Risk of NAFLD, OR (95 % CI)

Total Mean g /day Median g /dayInterquartilerange g /day Q1 Q2 Q3 Q4

P valuefor trend

Western pattern 1.00 1.25 (0.76 2.08) 1.97 (1.09 3.55) b 2.64 (1.34 5.18) b 0.030

Soft drinks 266.7 197.2 65.7 370.0 1.00 1.41 (0.82 2.43) 1.64 (0.94 2.86) 1.93 (1.04 3.56) b 0.188

Full-fat dairy 298.5 158.5 57.1 456.5 1.00 0.90 (0.55 1.47) 0.74 (0.44 1.23) 0.61 (0.33 1.14) 0.398

Rened grains 184.4 168.5 119.3 232.3 1.00 0.79 (0.48 1.31) 0.58 (0.33 1.01) 0.96 (0.52 1.76) 0.195

Red meat 62.1 57.4 37.7 80.4 1.00 0.98 (0.60 1.61) 0.76 (0.44 1.31) 0.94 (0.51 1.75) 0.760

Takeaway foods 58.9 49.2 29.3 78.8 1.00 0.85 (0.51 1.42) 0.72 (0.40 1.27) 0.96 (0.51 1.82) 0.635

Potato, not fried 50.3 44.6 26.8 64.5 1.00 1.43 (0.85 2.40) 0.87 (0.49 1.54) 1.28 (0.73 2.25) 0.242

Confectionary 43.4 30.6 15.0 54.3 1.00 0.86 (0.51 1.45) 1.14 (0.67 1.96) 1.12 (0.61 2.05) 0.745

Processed meats 34.1 29.3 15.7 47.3 1.00 0.88 (0.52 1.48) 1.21 (0.71 2.05) 1.27 (0.71 2.28) 0.556

Cakes, biscuits 31.1 25.8 12.3 43.8 1.00 0.79 (0.47 1.32) 1.05 (0.63 1.76) 1.05 (0.58 1.90) 0.686

Potato, fried chips 14.7 13.6 6.3 20.4 1.00 1.17 (0.67 2.04) 0.83 (0.49 1.42) 0.78 (0.42 1.48) 0.560

Sauces, dressings 11.0 8.6 2.9 14.3 1.00 1.65 (0.97 2.80) 0.78 (0.43 1.40) 1.95 (1.12 3.41) b 0.003

Crisps 8.7 4.3 2.0 12.9 1.00 0.81 (0.45 1.46) 0.68 (0.40 1.15) 1.03 (0.54 1.99) 0.307

CI, condence interval; NAFLD, nonalcoholic fatty liver disease; OR, odds ratio; Q , quartile.a Adjusted for western dietary pattern, healthy dietary pattern, sex, misreporting, TV viewing, frequency of physical activity, and family income.b Individual quartile compared with reference quartile, P < 0.05.



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CONFLICT OF INTERESTGuarantor of the article : Wendy H. Oddy, BAppSci, MPH, PhD.Speci c author contributions : W.H.O. was responsible or thecollection o nutrition data, coordinated the data analysis,interpreted the data, and wrote the manuscript; C.H. conducted thestatistical analyses and contributed to the interpretation o resultsand manuscript preparation; P.J. advised on the statistical analysis;G.L.A. derived the dietary patterns and contributed to manuscriptpreparation; .A.OS. contributed to interpretation o results andmanuscript preparation; L.A.A., O. .A., J.K.O., L.J.B., B.H., and

.A.M. contributed to study design, data collection and analysis,interpretation o results, and manuscript preparation.Financial support : Te Raine Study is unded by the University oWestern Australia (UWA), the Raine Medical Research Foundation,the National Health and Medical Research Council o Australia(NHMRC), the elethon Institute or Child Health Research, theUWA Faculty o Medicine, Dentistry and Health Sciences, Womensand In ants Research Foundation, and Curtin University.

Speci cally, the study was supported by NHMRC grant IDs 353514403981, and 634445, the Commonwealth Scienti c and IndustrialResearch Organisation, and the Australian Heart Foundation/ Beyond Blue Strategic Research Initiative (ID G08P4036). JohnK. Olynyk is the recipient o a NHMRC Practitioner Fellowship(1042370), Wendy H. Oddy is the recipient o an NHMRC Popula-tion Health Fellowship, and revor A. Mori is the recipient o anNHMRC Senior Research Fellowship. Gina Ambrosini is supportedby an MRC program grant (U105960389 Nutrition and Health).Potential competing interests : None.

Study Highlights

WHAT IS CURRENT KNOWLEDGE 3 Nonalcoholic fatty liver disease (NAFLD) is linked to

obesity but many patients have a normal body mass index(BMI).

3 Particular dietary components increasing risk are poorlydocumented.

WHAT IS NEW HERE 3 A Western style diet increased the risk of NAFLD in a

population cohort of adolescents.3 In adolescents with central obesity, a healthy dietary

pattern reduced the risk of NAFLD, whereas a Westerndietary pattern increased the risk of NAFLD.

REFERENCES1. Schwimmer JB, Deutsch R, Kahen et al. Prevalence o atty liver in

children and adolescents. Pediatrics 2006;118:138893.2. Malik SM, deVera ME, Fontes Pet al. Outcome afer liver transplantation

or NASH cirrhosis. Am J ransplant 2009;9:78293.3. Ayonrinde O , Olynyk JK, Beilin LJet al. Gender speci c differences in

adipose distribution and adipocytokines in uence adolescent NAFLD.Hepatology 2011;53:8009.

4. De Ferranti SD, Osganian SK. Epidemiology o paediatric metabolicsyndrome and type 2 diabetes mellitus. Diab Vasc Dis Res 2007;4:2834.

5. Kopelman PG, Grace C. New thoughts on managing obesity: recentadvances in clinical practice. Gut 2004;53:104453.

6. Hu FB. Dietary pattern analysis: a new direction in nutritionalepidemiology. Curr Opin Lipidol 2002;13:39.

possible that some o the oods o the Western dietary patterniconsumed in large serving sizesmay cause rapidly increasedplasma glucose levels, which may translate into hepatic at viathe de novo lipogenesis pathway (39). Indeed, in one study, obesesubjects with raised insulin levels had a higher rate ode novo lipogenesis compared with lean individuals when ed the sameWestern style diet (40).

We ound that the Western dietary pattern was signi cantlyassociated with greater measures o anthropometry. Te Westerndietary pattern contains high concentrations o saturated, trans,and monounsaturated ats (13), and animal models indicate thatthese ats may play a role in hepatic steatosis (41,42). Fat accumu-lation occurs in the liver via chylomicron uptake afer dietary atintake, as well as viade novo synthesis o ree atty acids ollowingdietary carbohydrate intake (43). Tere are ew other studies con-sidering dietary patterns and NAFLD in adolescents.

Our study bene ts rom being a population-based study in whicha range o in ormation on sociodemographic actors, physical activ-

ity, and sedentary behavior has been collected, thus allowing a thor-ough investigation o possible covariates. Our dietary patterns weresimilar to those described by others (16). We have previously shownthat, when compared with a 3-day ood record, our FFQ classi ed80 to 90% o subjects nutrient intakes into the same or adjacenttertile as their ood record and the FFQ was able to correctly rank areasonable proportion o adolescents (15). In addition, we control-led or dietary misreporting using a standard method. Although wedo not report 17-year dietary patterns with NAFLD at 17 years inthis article, in previous cross-sectional analyses in the same cohortat 14 years, we showed that the Western dietary pattern was associ-ated with cardiovascular risk actors and the clustering o these risk

actors (30). Furthermore, in support o our prospective ndingsthat a high Western dietary pattern was associated with the risk oNAFLD in the general population, Ambrosiniet al. (10) showed inchildren rom 7 to 15 years o age that intake o a dietary patterncharacterized by dietary energy density, percent total energy rom

at, and ber density in the years be ore measurement o at masswere signi cantly associated with later adiposity in adolescence.

In conclusion, a higher score or a Western dietary pattern at 14years o age was prospectively associated with NAFLD at 17 years,

ollowing adjustment or sex, dietary misreporting, amily income,physical activity, and sedentary behavior. Tis relationship appearsto be acting through obesity, suggesting that efforts to reduce obes-ity in childhood and adolescence may be important or preventingthe early development o NAFLD. Among centrally obese adoles-cents with NAFLD, those with a Western dietary pattern may bemore vulnerable to developing NAFLD, whereas a healthy dietarypattern may be protective against NAFLD.

ACKNOWLEDGMENTSWe thank the Raine Study participants, their amilies, and theRaine Study executive and staff. We would speci cally acknowledgethe NHMRC grants ID 353514, 403981, and 634445, the Common-wealth Scienti c and Industrial Research Organisation and theAustralian Heart Foundation/Beyond Blue Strategic ResearchInitiative or supporting this research (ID G08P4036).


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43. Donnelly KL, Smith CI, Schwarzenberg SJet al. Sources o atty acids storedin liver and secreted via lipoproteins in patients with nonalcoholic attyliver disease. J Clin Invest 2005;115:134351.

western diet and fatty liver

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