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Supplemental MaterialStudy exclusion rationalesTable S1. Studies excluded from meta-regression analysisStudyReason for exclusionAdams et al. (2010)Did not report TFA intake as %enAlmendingen et al. (1995)RuminantAscherio et al. (1999)ReviewBaer et al. (2004)Health outcome is markers of inflammation only, no LDL-C measurementBendsen et al. (2011)Diet not controlledChardigny et al. (2006)Reports the study design and methods for Chardigny et al. (2008), no post-diet health outcomeChardigny et al. (2008)RuminantChristiansen et al. (1997)RuminantCuchel et al. (1996)Duplicate of Lichtenstein et al. (1993)Denke et al. (2000)RuminantDenke and Grundy (1991)Did not report TFA intake as %ende Roos et al. (2001b)Duplicate of de Roos et al. (2001a)de Roos et al. (2002a)Study diet <3 weeks and TFA intake not reported as %ende Roos et al. (2002b)Duplicate of de Roos et al. (2001a)de Roos et al. (2003)Re-statement of de Roos et al. 2001a,b and 2002a,b study results Desroches et al. (2005)Did not report TFA intake as %enDyerberg et al. (2004)Fish OilFrench et al. (2002)Duplicate of the Sundram et al. studies (Sundram et al., 1997, 2003, 2007)Gurdeniz et al. (2013)Does not measure LDL-CHalvorsen et al. (1996)Study diet < 3 weeksIggman et al. (2011)RuminantJudd and Clevidence (1993)Same study as Judd et al. (1994)Labonte et al. (2011)RuminantLacroix et al. (2012)RuminantLecerf et al. (2009)Did not report TFA intake as %enLewington et al. (2007)Meta-analysisLichtenstein et al. (2001)Same population and results as Lichtenstein et al. (1999)Lichtenstein et al. (2003)Same population as Lichtenstein et al. (1999); report of non-fasting LDL-C measurementsLouheranta et al. (1999)Although Louheranta et al. (1999) has one diet that meets the inclusion criteria, there is no low-TFA comparator diet Mascioli et al. (1999)Did not report TFA intake as %enMatheson et al. (1996)Did not report TFA intake as %enMatthan et al. (2000b)No LDL-C measurementMatthan et al. (2001)Duplicate of Matthan et al. (2000a)Matthan et al. (2004)Likely subset of Han et al. (2002)Mensink et al. (1992)Duplicate of Mensink and Katan (1990) and Zock and Katan (1992)Mensink (2007)Diet not controlledMotard-Belanger et al. (2008)RuminantMozaffarian and Clarke (2009)Meta-analysisMozaffarian et al. (2006)Meta-analysisMuller et al. (1998a)Study diet <3 weeksMuller et al. (1998b)Study diet <3 weeksMuller et al. (2001)No LDL-C measurementMutanen and Aro (1997)No LDL-C measurementNestel et al. (1992)Diet not controlledNoakes and Clifton (1998)Did not report TFA intake as %en; diet not controlled?hrvall et al. (2001)Did not report TFA intake as %enPedersen et al. (2005)Study diet <3 weeksSanders et al. (2003)Study diet <3 weeksSundram et al. (1997)Diet only partially controlledSundram et al. (2003)Diet only partially controlledTakeuchi et al. (2011)Diet only partially controlledTakeuchi et al. (2011)Diet not controlledTakeuchi et al. (2012)Not a randomized controlled trialTeng et al. (2010)Diet only partially controlledTholstrup et al. (2006)Did not report TFA intake as %enTholstrup et al. (1994)Did not report TFA intake as %enThomsen et al. (1999)Study diet <3 weeksTonstad et al. (2001)Did not report TFA intake as %enTricon et al. (2006)Did not report TFA intake as %envan Tol et al. (1995)No LDL-C measurementVega-López et al. (2009)No information on subfractions of fatty acids; could not calculate adjusted ΔLDLVidgren et al. (1998)No LDL-C measurementWardlaw et al. (1995)Did not report TFA intake as %enWerner et al. (2013)Did not report TFA intake as %enWeststrate and Meijer (1998)Did not report TFA intake as %enModeling input dataTable S2. Modeling input dataStudyPopulation StatisticsTFA1 SourceTFA1LDL1TFA2 SourceTFA2LDL2ΔTFAActual ΔLDL-CPredicted ΔLDL-CActual-PredictedWeightWeight as %Notes on Assumptions Made When Fatty Acid %en Calculations Were RequiredSample Size% femaleMeanAgeMeanBMIAro et al. (1997)4061%2922.7Stearic acid - sunflower oil0.42.89Sunflower oil - TFA8.73.138.30.240.0550.2933.001.26%C12:C16 was calculated by determining the % contribution C14 and C16 to total fat fraction (Table 3) and then using that percentage with total fat percentage (Table 2). No data were provided for C12. MUFA calculated as oleic and palmitoleic acids from Table 3. PUFA was calculated by adding LA and ALA from Table 3. Han et al. (2002)1958%64.728.8Soybean oil0.63.89Soybean oil-based margarine6.74.336.10.440.1750.2713.180.50%Added Sat %en for C12 and C16. C14 was 0.1%en so was not included. Used cis-oleic as the MUFA because no information provided on trans-MUFA. PUFA was addition of C18:2 and C18:3 (LA and ALA). Report suggested only trans present was PUFA trans; however, no confirmation that the total MUFA did not included some transJudd et al. (1998)4650%46.825.3Sunflower oil and fully hydrogenated soybean oil2.43.21Partially hydrogenated soybean oil3.93.271.50.060.0400.0261.512.35%Added C12, C14, and C16 per author's information. Oleic, stearate as reported in publication (compared to author's info and was the same). PUFA added LA and ALA per author's infoJudd et al. (1994)5850%42.626.4Oleic0.73.34Mod trans (hydrogenated veg. oil)3.83.543.10.20.0230.18473.5918.07%PUFA is represented by LA. Other fats contains SCFA, Sat > 18, and some cis isomers of MUFA and PUFA other than oleic and LA. Other FA consistent across interventionsJudd et al. (1994)5850%42.626.4Oleic0.73.34High trans (hydrogenated veg. oil)6.63.65.90.260.0510.21471.7118.00%PUFA is represented by LA. Other fats contains SCFA, Sat > 18, and some cis isomers of MUFA and PUFA other than oleic and LA. Other FA consistent across interventionsJudd et al. (1994)5850%42.626.4Oleic0.73.34Coconut oil (sat)0.73.6400.30.315-0.02471.7118.00%PUFA is represented by LA. Other fats contains SCFA, Sat > 18, and some cis isomers of MUFA and PUFA other than oleic and LA. Other FA consistent across interventionsJudd et al. (2002)500%4226.2OL0.12.95TFA8.33.368.20.410.1350.2874.922.86%PUFA is represented by LA. Other fats contains SCFA, Sat > 18, and some cis isomers of MUFA and PUFA other than oleic and LA. Other FA consistent across interventionsJudd et al. (2002)500%4226.2OL0.12.95TFA|STE4.23.324.10.370.1310.2472.272.76%PUFA is represented by LA. Other fats contains SCFA, Sat > 18, and some cis isomers of MUFA and PUFA other than oleic and LA. Other FA consistent across interventionsJudd et al. (2002)500%4226.2OL0.12.95STE0.33.100.20.150.1370.0272.272.76%Judd et al. (2002)500%4226.2OL0.12.95LMP0.23.210.10.260.4300.1772.272.76%Lichtenstein et al. (1993)1457%6327.4Corn oil0.443.24Corn oil margarine4.163.503.720.260.0760.1824.720.95%Article lists other cis-MUFA fractions at low level (0.3)Lichtenstein et al. (1999)3650%6327.4Soybean oil0.553.99Semiliquid margarine0.914.010.360.0260.0080.0235.401.35%cis-PUFA included LA and ALA. Other cis-MUFA beside oleic present at 0.9–2.4 across the interventionsLichtenstein et al. (1999)3650%6327.4Soybean oil0.553.99Soft margarine3.34.122.750.130.0550.0736.681.40%Lichtenstein et al. (1999)3650%6327.4Soybean oil0.553.99Shortening4.154.253.60.260.1090.1534.161.30%Lichtenstein et al. (1999)3650%6327.4Soybean oil0.553.99Stick margarine6.724.356.170.360.1780.1831.811.21%Lichtenstein et al. (2006)3053%6326.2HiOleic-SO0.333.7Soybean oil0.613.660.280.040.0000.0433.851.29%C12:0-C16:0 total %en was calculated by subtracting C18:0 %en from total SFA %en. No C12 was provided; however, comparison of calculations across the interventions indicated that the addition of C14 and C16 was approximately 2/3 of the values obtained by subtraction (range, 0.68– 0.77% of the subtraction values). cis-PUFA (no EPA/DHA)%en was calculated by subtracting trans-PUFA %en from total PUFA %en. cis-MUFA was obtained by subtracting elaidic from total MUFA (majority is oleic with small amount of other).TFA determined by adding trans 18:2n and 18:3n and elaidic acidLichtenstein et al. (2006)3053%6326.2HiOleic-SO0.333.7LoSFA-SO0.643.530.310.170.0890.0829.121.11%C12:0-C16:p0 total %en was calculated by subtracting C18:0 %en from total SFA %en. No C12 was provided; however, comparison of calculations across the interventions indicated that the addition of C14 and C16 was approximately 2/3 of the values obtained by subtraction (range, 0.68–0.77% of the subtraction values). cis-PUFA (no EPA/DHA)%en was calculated by subtracting trans-PUFA fatty acids %en from total PUFA %en. TFA determined by adding trans 18:2n and 18:3n and elaidic acidLichtenstein et al. (2006)3053%6326.2HiOleic-SO0.333.7LoALA-SO0.523.710.190.010.0190.0335.421.35%C12:0-C16:0 total %en was calculated by subtracting C18:0 %en from total SFA %en. No C12 was provided; however, comparison of calculations across the interventions indicated that the addition of C14 and C16 was approximately 2/3 of the values obtained by subtraction (range, 0.68–0.77% of the subtraction values). cis-PUFA (no EPA/DHA)%en was calculated by subtracting trans-PUFA %en from total PUFA %en. TFA determined by adding trans 18:2n and 18:3n and elaidic acidLichtenstein et al. (2006)3053%6326.2HiOleic-SO0.333.70Partially hydrogenated soybean oil2.523.922.190.220.0840.1432.351.23%C12:0-C16:0 total %en was calculated by subtracting C18:0 %en from total SFA %en. No C12 was provided; however, comparison of calculations across the interventions indicated the addition of C14 and C16 was approximately 2/3 of the values obtained by subtraction (range, 0.68– 0.77% of the subtraction values). cis-PUFA (no EPA/DHA)%en was calculated by subtracting trans-PUFA %en from total PUFA %en. TFA determined by adding trans 18:2n and 18:3n and elaidic acidMatthan et al. (2000a)14100%68.126.5Soybean oil0.554.05Squeeze margarine0.914.070.360.0190.0070.0113.440.51%Fat composition taken from Matthan et al. (2000a). MUFA included all cis-MUFA. PUFA included all cis-PUFA. C12:C16 was provided and addedMatthan et al. (2000a)14100%68.126.5Soybean oil0.554.05Tub margarine3.34.282.750.230.0470.1810.930.42%Fat composition taken from Matthan et al. (2000a). MUFA included all cis-MUFA. PUFA included all cis-PUFA. C12:C16 was provided and addedMatthan et al. (2000a)14100%68.126.5Soybean oil0.554.05Stick margarine6.724.456.170.400.1600.2410.600.40%Fat composition taken from Matthan et al. (2000a). MUFA included all cis-MUFA. PUFA included all cis-PUFA. C12:C16 was provided and addedVega-López et al. (2006)1567%63.926Soybean oil0.553.76Partially hydrogenated soybean oil4.154.203.60.440.0830.3616.430.63%Soybean oil was the same intervention as in Matthan (2000a). These authors did not indicate total MUFA and total PUFA were only cis isomers; however, comparing the soybean oil and the indentation format in the report, the total MUFA and total PUFA appeared to be consistent with including only cis isomers. Therefore, these numbers were used for MUFA and PUFA calculationsVega-López et al. (2006)1567%63.926Soybean oil0.553.76Canola oil0.983.630.430.130.060.0720.210.77%Soybean oil was the same intervention as in Matthan (2000a). These authors did not indicate total MUFA and total PUFA were only cis isomers; however, comparing the soybean oil and the indentation format in the report, the total MUFA and total PUFA appeared to be consistent with including only cis isomers. Therefore, these numbers were used for MUFA and PUFA calculationsVega-López et al. (2006)1567%63.926Soybean oil0.553.76Palm oil0.64.270.050.520.460.0612.410.47%Soybean oil was the same intervention as in Matthan (2000a). These authors did not indicate total MUFA and total PUFA were only cis isomers; however, comparing the soybean oil and the indentation format in the report, the total MUFA and total PUFA appeared to be consistent with including only cis isomers. Therefore, these numbers were used for MUFA and PUFA calculationsWanders et al. (2010)6159%30.922.8Sunflower oil (high oleic acid diet)0.22.68Margarine (iTFA diet)7.537.30.320.3130.0174.072.83%Report does not provide total cis-MUFA or cis-PUFA. Oleic is provided and used for cis-MUFA. LA was provided and used for cis-PUFAde Roos et al. (2001a)3266%3022.8SFA - mix of rapeseed, soybean, sunflower oils, palm kernel fat, coconut, and palm oil0.33.05TFA general9.33.0490.010.390.3824.650.94%Different information is provided in duplicate study reports for cis-MUFA fraction. All other diet data are exactly the same. cis-MUFA was taken from de Roos et al. (2001a), which was the report that contained the cholesterol data. The other paper was de Roos et al. (2001b). Total trans in the de Roos et al. (2001a) article is 0.4 and 9.4, although it was 0.3 and 9.3 for the low and high trans groups, respectively, in de Roos et al. (2001b). Oleic was used for cis-MUFA, and cis-PUFA was determined by addition of LA and ALAMensink and Katan (1990)5958%25.522Sunflower oil/olive oil high oleic02.67Sunflower oil margarine high TFA113.04110.370.170.2088.443.37%Oleic was used for cis-MUFA. LA was used for cis-PUFA. Sat fat was addition of C12, C14, and C16Mensink and Katan (1990)a5958%25.522Sunflower oil/olive oil high oleic02.67Margarine/palm oil high SFA0.83.140.80.470.530.06Oleic was used for cis-MUFA. LA was used for cis-PUFA. Sat fat was addition of C12, C14, and C16Zock et al. (1994)5961%28.522.4Palm oil, cotton seed oil, fully hydrogenated sunflower oil0.22.98Myristic acid rich margarine0.83.090.60.110.030.0852.201.99%Trans is addition of elaidic (0.7) and trans isomers of C18:2. Oleic used for cis-MUFA, and LA for cis-PUFA because total MUFA and total PUFA did not indicate having exclusively cis isomersZock et al. (1994)5961%28.522.4Palm oil, cotton seed oil, fully hydrogenated sunflower oil0.22.98Sunflower oil0.32.60.10.380.540.1657.512.19%Trans is addition of elaidic (0.7) and trans isomers of C18:2. Oleic used for cis-MUFA, and LA for cis-PUFA because total MUFA and total PUFA did not indicate having exclusively cis isomersZock and Katan (1992)a5654%24-2521.5Sunflower oil0.12.83Fully hydrogenated sunflower oil0.330.20.170.200.03Oleic used for cis-MUFA, and LA for cis-PUFA because total MUFA and total PUFA did not indicate having exclusively cis isomersZock and Katan (1992)5654%24-2521.5Sunflower oil0.12.83Partially hydrogenated sunflower oil7.73.077.60.240.160.0868.072.60%Oleic used for cis-MUFA, and LA for cis-PUFA because total MUFA and total PUFA did not indicate having exclusively cis isomersLovejoy et al. (2002)2552%2823.5Monounsaturated diet02.15Trans diet7.32.247.30.090.200.1161.512.35%C12 and C16:1 shown in column with no data. Sat fat addition of C14 and C16. MUFA is addition of C16:1, cis C18:1, and cis C20:1. PUFA is LA. Fats were calculated as percent contribution of total fats first, and then that percent multiplied with total fat in the dietAbbreviations: ALA, alpha-linolenic acid; FA, fatty acids; LA, linoleic acid; LMP, 12:0-16:0 (lauric, myristic, and palmitic) saturated fatty acids; LoALA-SO, low-alpha-linolenic acid soybean oil; LoSFA-SO, low-saturated fatty acid soybean oil; OL, oleic acid; Sat, saturated; SCFA, short-chain fatty acid; SO, soybean oil; STE, stearic acid.aThese study arms are not included in the initial analysis and are used for sensitivity analyses only.Tests for normality of TFA-associated LDL changeTable S3. Tests for Normality of the Dependent Variable: TFA-Associated LDL Change (Observed Minus Predicted ΔLDL) TestStatisticp-ValueShapiro-WilkW0.976811Pr < W 0.6700Kolmogorov-SmirnovD0.112919Pr > D>0.1500Cramer-von MisesW-Sq0.064691Pr > W-Sq>0.2500Anderson-DarlingA-Sq0.333421Pr > A-sq>0.2500Figure S1. Graphical examination (Q-Q plot) for normality of the dependent variable TFA-associated LDL change (observed minus predicted ΔLDL). OpenBUGS model codesLinear Model:model {for( i in 1 : S ) {Obs[i] ~ dnorm(mu[i],tau[i])mu[i] <- a[study[i]] + b * tfa[i] tau[i] <- 1/Est[i]p[i] <- density(Obs[i], Obs[i])log_like[i] <- log(p[i])}#Section to define 1 (or more) random effect parameter; must be one of the parms used to define mu[i]#Comment or leave OUT the parms considered fixed effects over studiesfor( i in 1 : nstudies ) {a[i] ~ dnorm(0, a_tau) ap[i] <- density(a[i], a[i])alog_like[i] <- log(ap[i])}#In this section define priors for fixed effects and for hyper-mean of random effect (e.g., b_1)# a ~ dunif(.5, 1.5) # background no mean needed because assumed to be zero for this endpointb ~ dunif(0, 1) #slope parameter (beta)#F-dist for prior of StD of random effect parameter#d1 = 9, d2 = 3 ==> mode = 0.48 which is somewhat greater than max within-study std lsigma ~ df(9,3,0,1) a_tau <- 1/(lsigma*lsigma)lsigmalog_like <- log(density(lsigma, lsigma))}Hill Model:model {for( i in 1 : S ) {Obs[i] ~ dnorm(mu[i],tau[i])mu[i] <- a[study[i]] + v * pow(tfa[i], n) / (pow(tfa[i], n) + pow(k, n))tau[i] <- 1/Est[i]p[i] <- density(Obs[i], Obs[i])log_like[i] <- log(p[i])}#Section to define 1 (or more) random effect parameter; must be one of the parms used to define mu[i]#Comment or leave OUT the parms considered fixed effects over studiesfor( i in 1 : nstudies ) {a[i] ~ dnorm(0, a_tau) ap[i] <- density(a[i], a[i])alog_like[i] <- log(ap[i])}#In this section define priors for fixed effects and for hyper-mean of random effect (e.g., b_1)# a ~ dunif(.5, 1.5) # background no mean needed because assumed to be zero for this endpointv ~ dunif(0, 1) #max change (beta)n ~ dunif(1, 20) #Hill powerk ~ dunif(0.1, 6) #half-sat dose#F-dist for prior of StD of random effect parameter#d1 = 9, d2 = 3 ==> mode = 0.48 which is somewhat greater than max within-study stdlsigma ~ df(9,3,0,1) a_tau <- 1/(lsigma*lsigma)lsigmalog_like <- log(density(lsigma, lsigma))} Supplemental ReferencesAdams, T.H., Walzem, R.L., Smith, D.R., Tseng, S., Smith, S.B., 2010. 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