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1. Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies

Author

Harris, WS, Tintle, NL, Imamura, F, Qian, F, Korat, AVA, Marklund, M, Djousse, L, Bassett, JK, Carmichael, P-H, Chen, Y-Y, Hirakawa, Y, Kupers, LK, Laguzzi, F, Lankinen, M, Murphy, RA, Samieri, C, Senn, MK, Shi, P, Virtanen, JK, Brouwer, IA, Chien, K-L, Eiriksdottir, G, Forouhi, NG, Geleijnse, JM, Giles, GG, Gudnason, V, Helmer, C, Hodge, A, Jackson, R, Khaw, K-T, Laakso, M, Lai, H, Laurin, D, Leander, K, Lindsay, J, Micha, R, Mursu, J, Ninomiya, T, Post, W, Psaty, BM, Riserus, U, Robinson, JG, Shadyab, AH, Snetselaar, L, Sala-Vila, A, Sun, Y, Steffen, LM, Tsai, MY, Wareham, NJ, Wood, AC, Wu, JHY, Hu, F, Sun, Q, Siscovick, DS, Lemaitre, RN, Mozaffarian, D, Harris, WS, Tintle, NL, Imamura, F, Qian, F, Korat, AVA, Marklund, M, Djousse, L, Bassett, JK, Carmichael, P-H, Chen, Y-Y, Hirakawa, Y, Kupers, LK, Laguzzi, F, Lankinen, M, Murphy, RA, Samieri, C, Senn, MK, Shi, P, Virtanen, JK, Brouwer, IA, Chien, K-L, Eiriksdottir, G, Forouhi, NG, Geleijnse, JM, Giles, GG, Gudnason, V, Helmer, C, Hodge, A, Jackson, R, Khaw, K-T, Laakso, M, Lai, H, Laurin, D, Leander, K, Lindsay, J, Micha, R, Mursu, J, Ninomiya, T, Post, W, Psaty, BM, Riserus, U, Robinson, JG, Shadyab, AH, Snetselaar, L, Sala-Vila, A, Sun, Y, Steffen, LM, Tsai, MY, Wareham, NJ, Wood, AC, Wu, JHY, Hu, F, Sun, Q, Siscovick, DS, Lemaitre, RN, and Mozaffarian, D

Abstract

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.

Published
2021

2. Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies

Author

Imamura, F, Fretts, AM, Marklund, M, Ardisson Korat, AV, Yang, WS, Lankinen, M, Qureshi, W, Helmer, C, Chen, TA, Virtanen, JK, Wong, K, Bassett, JK, Murphy, R, Tintle, N, Yu, CI, Brouwer, IA, Chien, KL, Chen, YY, Wood, AC, del Gobbo, LC, Djousse, L, Geleijnse, JM, Giles, GG, de Goede, J, Gudnason, V, Harris, WS, Hodge, A, Hu, F, Koulman, A, Laakso, M, Lind, L, Lin, HJ, McKnight, B, Rajaobelina, K, Riserus, U, Robinson, JG, Samieri, C, Senn, M, Siscovick, DS, Soedamah-Muthu, SS, Sotoodehnia, N, Sun, Q, Tsai, MY, Tuomainen, TP, Uusitupa, M, Wagenknecht, LE, Wareham, NJ, Wu, JHY, Micha, R, Lemaitre, RN, Mozaffarian, D, Forouhi, NG, Imamura, F, Fretts, AM, Marklund, M, Ardisson Korat, AV, Yang, WS, Lankinen, M, Qureshi, W, Helmer, C, Chen, TA, Virtanen, JK, Wong, K, Bassett, JK, Murphy, R, Tintle, N, Yu, CI, Brouwer, IA, Chien, KL, Chen, YY, Wood, AC, del Gobbo, LC, Djousse, L, Geleijnse, JM, Giles, GG, de Goede, J, Gudnason, V, Harris, WS, Hodge, A, Hu, F, Koulman, A, Laakso, M, Lind, L, Lin, HJ, McKnight, B, Rajaobelina, K, Riserus, U, Robinson, JG, Samieri, C, Senn, M, Siscovick, DS, Soedamah-Muthu, SS, Sotoodehnia, N, Sun, Q, Tsai, MY, Tuomainen, TP, Uusitupa, M, Wagenknecht, LE, Wareham, NJ, Wu, JHY, Micha, R, Lemaitre, RN, Mozaffarian, D, and Forouhi, NG

Abstract

Background De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D). Methods and findings Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970-1973 to 2006-2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3-75.5 years; % women = 20.4%-62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41-1.66; p < 0.001) for 16:0, 1.40 (1.33-1.48; p < 0.001) for 16:1n-7, 1.14 (1.05-1.22; p = 0.001) for 18:0, and 1.16 (1.07-1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%-73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94-1.13). These findings had limitations in potential reverse causation and residual confounding by impreci

Published
2020

3. Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies

Author

Lin, X, Imamura, F, Fretts, AM, Marklund, M, Ardisson Korat, AV, Yang, W-S, Lankinen, M, Qureshi, W, Helmer, C, Chen, T-A, Virtanen, JK, Wong, K, Bassett, JK, Murphy, R, Tintle, N, Yu, CI, Brouwer, IA, Chien, K-L, Chen, Y-Y, Wood, AC, del Gobbo, LC, Djousse, L, Geleijnse, JM, Giles, GG, de Goede, J, Gudnason, V, Harris, WS, Hodge, A, Hu, F, Koulman, A, Laakso, M, Lind, L, Lin, H-J, McKnight, B, Rajaobelina, K, Riserus, U, Robinson, JG, Samieri, C, Senn, M, Siscovick, DS, Soedamah-Muthu, SS, Sotoodehnia, N, Sun, Q, Tsai, MY, Tuomainen, T-P, Uusitupa, M, Wagenknecht, LE, Wareham, NJ, Wu, JHY, Micha, R, Lemaitre, RN, Mozaffarian, D, Forouhi, NG, Lin, X, Imamura, F, Fretts, AM, Marklund, M, Ardisson Korat, AV, Yang, W-S, Lankinen, M, Qureshi, W, Helmer, C, Chen, T-A, Virtanen, JK, Wong, K, Bassett, JK, Murphy, R, Tintle, N, Yu, CI, Brouwer, IA, Chien, K-L, Chen, Y-Y, Wood, AC, del Gobbo, LC, Djousse, L, Geleijnse, JM, Giles, GG, de Goede, J, Gudnason, V, Harris, WS, Hodge, A, Hu, F, Koulman, A, Laakso, M, Lind, L, Lin, H-J, McKnight, B, Rajaobelina, K, Riserus, U, Robinson, JG, Samieri, C, Senn, M, Siscovick, DS, Soedamah-Muthu, SS, Sotoodehnia, N, Sun, Q, Tsai, MY, Tuomainen, T-P, Uusitupa, M, Wagenknecht, LE, Wareham, NJ, Wu, JHY, Micha, R, Lemaitre, RN, Mozaffarian, D, and Forouhi, NG

Abstract

BACKGROUND: De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D). METHODS AND FINDINGS: Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970-1973 to 2006-2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3-75.5 years; % women = 20.4%-62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41-1.66; p < 0.001) for 16:0, 1.40 (1.33-1.48; p < 0.001) for 16:1n-7, 1.14 (1.05-1.22; p = 0.001) for 18:0, and 1.16 (1.07-1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%-73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94-1.13). These findings had limitations in potential reverse causation and residual confounding by impre

Published
2020

4. Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies

Author

Marklund, M, Wu, JHY, Imamura, F, Del Gobbo, LC, Fretts, A, De Goede, J, Shi, P, Tintle, N, Wennberg, M, Aslibekyan, S, Chen, TA, De Oliveira Otto, MC, Hirakawa, Y, Eriksen, HH, Kröger, J, Laguzzi, F, Lankinen, M, Murphy, RA, Prem, K, Samieri, C, Virtanen, J, Wood, AC, Wong, K, Yang, WS, Zhou, X, Baylin, A, Boer, JMA, Brouwer, IA, Campos, H, Chaves, PHM, Chien, KL, De Faire, U, Djoussé, L, Eiriksdottir, G, El-Abbadi, N, Forouhi, NG, Michael Gaziano, J, Geleijnse, JM, Gigante, B, Giles, G, Guallar, E, Gudnason, V, Harris, T, Harris, WS, Helmer, C, Hellenius, ML, Hodge, A, Hu, FB, Jacques, PF, Jansson, JH, Kalsbeek, A, Khaw, KT, Koh, WP, Laakso, M, Leander, K, Lin, HJ, Lind, L, Luben, R, Luo, J, Mcknight, B, Mursu, J, Ninomiya, T, Overvad, K, Psaty, BM, Rimm, E, Schulze, MB, Siscovick, D, Skjelbo Nielsen, M, Smith, AV, Steffen, BT, Steffen, L, Sun, Q, Sundström, J, Tsai, MY, Tunstall-Pedoe, H, Uusitupa, MIJ, Van Dam, RM, Veenstra, J, Monique Verschuren, WM, Wareham, N, Willett, W, Woodward, M, Yuan, JM, Micha, R, Lemaitre, RN, Mozaffarian, D, Risérus, U, Marklund, M, Wu, JHY, Imamura, F, Del Gobbo, LC, Fretts, A, De Goede, J, Shi, P, Tintle, N, Wennberg, M, Aslibekyan, S, Chen, TA, De Oliveira Otto, MC, Hirakawa, Y, Eriksen, HH, Kröger, J, Laguzzi, F, Lankinen, M, Murphy, RA, Prem, K, Samieri, C, Virtanen, J, Wood, AC, Wong, K, Yang, WS, Zhou, X, Baylin, A, Boer, JMA, Brouwer, IA, Campos, H, Chaves, PHM, Chien, KL, De Faire, U, Djoussé, L, Eiriksdottir, G, El-Abbadi, N, Forouhi, NG, Michael Gaziano, J, Geleijnse, JM, Gigante, B, Giles, G, Guallar, E, Gudnason, V, Harris, T, Harris, WS, Helmer, C, Hellenius, ML, Hodge, A, Hu, FB, Jacques, PF, Jansson, JH, Kalsbeek, A, Khaw, KT, Koh, WP, Laakso, M, Leander, K, Lin, HJ, Lind, L, Luben, R, Luo, J, Mcknight, B, Mursu, J, Ninomiya, T, Overvad, K, Psaty, BM, Rimm, E, Schulze, MB, Siscovick, D, Skjelbo Nielsen, M, Smith, AV, Steffen, BT, Steffen, L, Sun, Q, Sundström, J, Tsai, MY, Tunstall-Pedoe, H, Uusitupa, MIJ, Van Dam, RM, Veenstra, J, Monique Verschuren, WM, Wareham, N, Willett, W, Woodward, M, Yuan, JM, Micha, R, Lemaitre, RN, Mozaffarian, D, and Risérus, U

Abstract

Background: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. Methods: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). Results: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extrem

Published
2019

5. Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies

Author

Imamura, F, Fretts, A, Marklund, M, Ardisson Korat, AV, Yang, WS, Lankinen, M, Qureshi, W, Helmer, C, Chen, TA, Wong, K, Bassett, JK, Murphy, R, Tintle, N, Yu, CI, Brouwer, IA, Chien, KL, Fraizier-Wood, AC, Del Gobbo, LC, Djousse, L, Geleijnse, JM, Giles GG, de Goede, J, Gudnason, V, Harris, WS, Hodge, A, Hu, F, InterAct Consortium, Koulman, A, Laakso, M, Lind, L, Lin, HJ, McKnight, B, Rajaobelina, K, Risérus, U, Robinson, JG, Samieri, C, Siscovick, DS, Soedamah-Muthu, SS, Sotoodehnia, N, Sun, Q, Tsai, MY, Uusitupa, M, Wagenknecht, LE, Wareham, NJ, Wu, J, Micha, R, Forouhi, NG, Lemaitre, RN, Mozaffarian, D, Fatty Acids and Outcomes Research Consortium (FORCE, Imamura, F, Fretts, A, Marklund, M, Ardisson Korat, AV, Yang, WS, Lankinen, M, Qureshi, W, Helmer, C, Chen, TA, Wong, K, Bassett, JK, Murphy, R, Tintle, N, Yu, CI, Brouwer, IA, Chien, KL, Fraizier-Wood, AC, Del Gobbo, LC, Djousse, L, Geleijnse, JM, Giles GG, de Goede, J, Gudnason, V, Harris, WS, Hodge, A, Hu, F, InterAct Consortium, Koulman, A, Laakso, M, Lind, L, Lin, HJ, McKnight, B, Rajaobelina, K, Risérus, U, Robinson, JG, Samieri, C, Siscovick, DS, Soedamah-Muthu, SS, Sotoodehnia, N, Sun, Q, Tsai, MY, Uusitupa, M, Wagenknecht, LE, Wareham, NJ, Wu, J, Micha, R, Forouhi, NG, Lemaitre, RN, Mozaffarian, D, and Fatty Acids and Outcomes Research Consortium (FORCE

Published
2018

6. Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies

Author

Hattersley, AT, Imamura, F, Fretts, A, Marklund, M, Korat, AVA, Yang, W-S, Lankinen, M, Qureshi, W, Helmer, C, Chen, T-A, Wong, K, Bassett, JK, Murphy, R, Tintle, N, Yu, CI, Brouwer, IA, Chien, K-L, Frazier-Wood, AC, del Gobbo, LC, Djousse, L, Geleijnse, JM, Giles, GG, de Goede, J, Gudnason, V, Harris, WS, Hodge, A, Hu, F, Koulman, A, Laakso, M, Lind, L, Lin, H-J, McKnight, B, Rajaobelina, K, Riserus, U, Robinson, JG, Samieri, C, Siscovick, DS, Soedamah-Muthu, SS, Sotoodehnia, N, Sun, Q, Tsai, MY, Uusitupa, M, Wagenknecht, LE, Wareham, NJ, Wu, JHY, Micha, R, Forouhi, NG, Lemaitre, RN, Mozaffarian, D, Hattersley, AT, Imamura, F, Fretts, A, Marklund, M, Korat, AVA, Yang, W-S, Lankinen, M, Qureshi, W, Helmer, C, Chen, T-A, Wong, K, Bassett, JK, Murphy, R, Tintle, N, Yu, CI, Brouwer, IA, Chien, K-L, Frazier-Wood, AC, del Gobbo, LC, Djousse, L, Geleijnse, JM, Giles, GG, de Goede, J, Gudnason, V, Harris, WS, Hodge, A, Hu, F, Koulman, A, Laakso, M, Lind, L, Lin, H-J, McKnight, B, Rajaobelina, K, Riserus, U, Robinson, JG, Samieri, C, Siscovick, DS, Soedamah-Muthu, SS, Sotoodehnia, N, Sun, Q, Tsai, MY, Uusitupa, M, Wagenknecht, LE, Wareham, NJ, Wu, JHY, Micha, R, Forouhi, NG, Lemaitre, RN, and Mozaffarian, D

Abstract

BACKGROUND: We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D). METHODS AND FINDINGS: Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73-0.87); of 17:0, 0.65 (0.59-0.72); of t16:1n7, 0.82 (0.70-0.96); and of their sum, 0.71 (0.63-0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist. CONCLUSIONS: In a larg

Published
2018

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