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1. List of Contributors

Author

Babenko, N.A., primary, Beken, S., additional, Bernoud-Hubac, N., additional, Birgisdottir, B.E., additional, Butt, C.M., additional, Chen, T.C., additional, Daschner, A., additional, Erkkilä, A., additional, Fell, G.L., additional, Fernandes, L.C., additional, Genot, C., additional, Grung, B., additional, Gura, K.M., additional, Hansen, A.L., additional, Harris, M.A., additional, Harris, W.S., additional, Hintze, K., additional, Ismail, A., additional, Jaczynski, J., additional, Jahns, L., additional, Kabataş, E.U., additional, Khan, M.W., additional, Khan, S.A., additional, Kris-Etherton, P.M., additional, Lammi-Keefe, C.J., additional, Lands, B., additional, Lankinen, M., additional, Lara, J., additional, Lean, M., additional, Lewis, M.D., additional, McLennan, P.L., additional, Meynier, A., additional, Michalski, M-C., additional, Peoples, G.E., additional, Picklo, M.J., additional, Priyamvada, S., additional, Puder, M., additional, Ramón Bonache, R., additional, Rice, H.B., additional, Richter, C.K., additional, Salem, N., additional, Seelaender, M., additional, Simopoulos, A.P., additional, Skulas-Ray, A.C., additional, Steffen, B.T., additional, Steffen, L.M., additional, Tørris, C., additional, Tahergorabi, R., additional, Thorsdottir, I., additional, Ulven, S.M., additional, von Schacky, C., additional, Ward, R., additional, Yusufi, A.N.K., additional, Yusufi, F.N. Khan, additional, and Zheng, S., additional

Published
2016
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3. 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 A.M., Marklund M., Ardisson Korat A.V., Yang W.-S., Lankinen M., Qureshi W., Helmer C., Chen T.-A., Virtanen J.K., Wong K., Bassett J.K., Murphy R., Tintle N., Yu C.I., Brouwer I.A., Chien K.-L., Chen Y.-Y., Wood A.C., del Gobbo L.C., Djousse L., Geleijnse J.M., Giles G.G., de Goede J., Gudnason V., Harris W.S., Hodge A., Hu F., Koulman A., Laakso M., Lind L., Lin H.-J., McKnight B., Rajaobelina K., Riserus U., Robinson J.G., Samieri C., Senn M., Siscovick D.S., Soedamah-Muthu S.S., Sotoodehnia N., Sun Q., Tsai M.Y., Tuomainen T.-P., Uusitupa M., Wagenknecht L.E., Wareham N.J., Wu J.H.Y., Micha R., Lemaitre R.N., Mozaffarian D., Forouhi N.G., Imamura F., Fretts A.M., Marklund M., Ardisson Korat A.V., Yang W.-S., Lankinen M., Qureshi W., Helmer C., Chen T.-A., Virtanen J.K., Wong K., Bassett J.K., Murphy R., Tintle N., Yu C.I., Brouwer I.A., Chien K.-L., Chen Y.-Y., Wood A.C., del Gobbo L.C., Djousse L., Geleijnse J.M., Giles G.G., de Goede J., Gudnason V., Harris W.S., Hodge A., Hu F., Koulman A., Laakso M., Lind L., Lin H.-J., McKnight B., Rajaobelina K., Riserus U., Robinson J.G., Samieri C., Senn M., Siscovick D.S., Soedamah-Muthu S.S., Sotoodehnia N., Sun Q., Tsai M.Y., Tuomainen T.-P., Uusitupa M., Wagenknecht L.E., Wareham N.J., Wu J.H.Y., Micha R., Lemaitre R.N., Mozaffarian D., and Forouhi N.G.

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
2021

4. N-3 fatty acid biomarkers and incident type 2 diabetes: An individual participant-level pooling project of 20 prospective cohort studies.

Author

Qian F., Ardisson Korat A.V., Imamura F., Marklund M., Tintle N., Virtanen J.K., Zhou X., Bassett J.K., Lai H., Hirakawa Y., Chien K.-L., Wood A.C., Lankinen M., Murphy R.A., Samieri C., Pertiwi K., de Mello V.D., Guan W., Forouhi N.G., Wareham N., Consortium I., Hu F.B., Riserus U., Lind L., Harris W.S., Shadyab A.H., Robinson J.G., Steffen L.M., Hodge A., Giles G.G., Ninomiya T., Uusitupa M., Tuomilehto J., Lindstrom J., Laakso M., Siscovick D.S., Helmer C., Geleijnse J.M., Wu J.H.Y., Fretts A., Lemaitre R.N., Micha R., Mozaffarian D., Sun Q., Qian F., Ardisson Korat A.V., Imamura F., Marklund M., Tintle N., Virtanen J.K., Zhou X., Bassett J.K., Lai H., Hirakawa Y., Chien K.-L., Wood A.C., Lankinen M., Murphy R.A., Samieri C., Pertiwi K., de Mello V.D., Guan W., Forouhi N.G., Wareham N., Consortium I., Hu F.B., Riserus U., Lind L., Harris W.S., Shadyab A.H., Robinson J.G., Steffen L.M., Hodge A., Giles G.G., Ninomiya T., Uusitupa M., Tuomilehto J., Lindstrom J., Laakso M., Siscovick D.S., Helmer C., Geleijnse J.M., Wu J.H.Y., Fretts A., Lemaitre R.N., Micha R., Mozaffarian D., and Sun Q.

Abstract

OBJECTIVE Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of a-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis. RESEARCH DESIGN AND METHODS For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance-weighted meta-analysis. RESULTS A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all P < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses. CONCLUSIONS Highercirculating biomarkers of seafood-derivedn-3 fattyacids, including EPA,DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.Copyright © 2021 by the American Diabetes Association.

Published
2021

5. n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies.

Author

Fretts A., Sun Q., Qian F., Ardisson Korat A.V., Imamura F., Marklund M., Tintle N., Mozaffarian D., Virtanen J.K., Zhou X., Bassett J.K., Lai H., Hirakawa Y., Chien K.-L., Wood A.C., Lankinen M., Murphy R.A., Samieri C., Micha R., Lemaitre R.N., Pertiwi K., de Mello V.D., Guan W., Forouhi N.G., Wareham N., Hu I.C.F.B., Riserus U., Lind L., Harris W.S., Shadyab A.H., Robinson J.G., Steffen L.M., Hodge A., Giles G.G., Ninomiya T., Uusitupa M., Tuomilehto J., Lindstrom J., Laakso M., Siscovick D.S., Helmer C., Geleijnse J.M., Wu J.H.Y., Fretts A., Sun Q., Qian F., Ardisson Korat A.V., Imamura F., Marklund M., Tintle N., Mozaffarian D., Virtanen J.K., Zhou X., Bassett J.K., Lai H., Hirakawa Y., Chien K.-L., Wood A.C., Lankinen M., Murphy R.A., Samieri C., Micha R., Lemaitre R.N., Pertiwi K., de Mello V.D., Guan W., Forouhi N.G., Wareham N., Hu I.C.F.B., Riserus U., Lind L., Harris W.S., Shadyab A.H., Robinson J.G., Steffen L.M., Hodge A., Giles G.G., Ninomiya T., Uusitupa M., Tuomilehto J., Lindstrom J., Laakso M., Siscovick D.S., Helmer C., Geleijnse J.M., and Wu J.H.Y.

Abstract

OBJECTIVE: Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis. RESEARCH DESIGN AND METHODS: For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance-weighted meta-analysis. RESULT(S): A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all P < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses. CONCLUSION(S): Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.Copyright © 2021 by the American Diabetes Association.

Published
2021

6. Erythrocyte omega-3 index, ambient fine particle exposure, and brain aging

Author

Kaufman, J.D., Chen, J.-C., Wang, X., He, K., Hayden, K.M., Chui, H.C., Vizuete, W., Espeland, M.A., Whitsel, E.A., Serre, M.L., Xun, P., Orchard, T., Harris, W.S., and Chen, C.

Abstract

OBJECTIVE: To examine whether long-chain omega-3 polyunsaturated fatty acid (LCn3PUFA) levels modify the potential neurotoxic effects of particle matter with diameters

Published
2020
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10. Conducting omega-3 clinical trials with cardiovascular outcomes: Proceedings of a workshop held at ISSFAL 2014

Author

Rice, H.B., Bernasconi, A., Maki, K.C., Harris, W.S., von Schacky, C., and Calder, P.C.

Abstract

In contrast to earlier long-chain (LC) omega-3 (i.e. EPA and DHA) investigations, some recent studies have not demonstrated significant effects of EPA and DHA on cardiovascular disease (CVD) outcomes. The neutral findings may have been due to experimental design issues, such as: maintenance on aggressive cardiovascular drug treatment overshadowing the benefits of LC omega-3s, high background LC omega-3 intake, too few subjects in the study, treatment duration too short, insufficient LC omega-3 dosage, increase in omega-6 fatty acid intake during the study, failure to assess the LC omega-3 status of the subjects prior to and during treatment and lack of clarity concerning which mechanisms were expected to produce benefits. At the 11th ISSFAL Congress, a workshop was held on conducting LC omega-3 clinical trials with cardiovascular outcomes, with the goal of gaining a better understanding concerning aspects of experimental design that should be considered when planning clinical studies related to EPA and DHA and potential cardiovascular benefits.

Published
2016

18. Omega-3 fatty acids modulate collagen signaling in human platelets

Author

Larson, M.K., primary, Shearer, G.C., additional, Ashmore, J.H., additional, Anderson-Daniels, J.M., additional, Graslie, E.L., additional, Tholen, J.T., additional, Vogelaar, J.L., additional, Korth, A.J., additional, Nareddy, V., additional, Sprehe, M., additional, and Harris, W.S., additional

Published
2011
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30. Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging

Author

Tan, Z.S., Harris, W.S., Beiser, A.S., Au, R., Himali, J.J., Debette, S., Pikula, A., DeCarli, C., Wolf, P.A., Vasan, R.S., Robins, S.J., and Seshadri, S.

Abstract

Higher dietary intake and circulating levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been related to a reduced risk for dementia, but the pathways underlying this association remain unclear. We examined the cross-sectional relation of red blood cell (RBC) fatty acid levels to subclinical imaging and cognitive markers of dementia risk in a middle-aged to elderly community-based cohort.

Published
2012
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31. Omega-3 long-chain PUFA and triglyceride lowering: minimum effective intakes

Author

Harris, W.S.

Abstract

Early studies on the cardioprotective effects of high doses (up to 20 g of eicosapentaenoic and docosahexaenoic acids, EPA and DHA, per day) of omega-3 fatty acids (FAs) suggested that these FAs primarily lowered triglyceride levels. These supraphysiological intake studies soon gave way to trials using lower and lower intakes of omega-3 FAs such that it is now clear that up to 45% lowering of serum triglyceride levels can be achieved with 3–4 g of EPA + DHA. This is an intake that can hardly be achieved by dietary means; direct supplementation is required. This is a public health challenge since implementing wide-scale supplementation programmes would be difficult. Relatively few investigators have examined the effects of low (<2 g) EPA+DHA on serum lipid profiles, presumably because until recently there was little expectation that any benefit would be detectable. With the publication of the DART study and more recently the GISSI-Prevenzione Study, it is becoming clear that small intakes of omega-3 FAs can significantly impact CHD risk. A review of the studies on the effects of small doses (<2 g · day−1) of omega-3 FAs on serum triglyceride levels suggests that serum triglyceride levels decreased in every study (compared with control or placebo treatment). The decreases were often not statistically significant, but this is to be expected with small doses given for short time-periods. Four of the five studies that examined postprandial lipids (PPL) reported significant reductions in this parameter even when fasting levels were not altered. This suggests that chronic intake of small amounts of omega-3 FAs may reduce overall (day-long) triglyceride-rich lipoprotein levels which could have long-term implications for the reduction of CHD risk. Whilst the cardioprotective effects of omega-3 FAs are becoming well documented, the question of whether such beneficial effects of omega-3 FAs are at least partially mediated by changes in serum levels of triglyceride-rich lipoproteins or their remnants remains open. Further studies to examine the effects of this low level of intake are clearly needed to determine the relative contribution of hypolipidaemic mechanisms versus those involving diminished platelet function, altered adhesion molecule expression, improvements in endothelial function and antiarrhythmic or hypotensive effects.

Published
2001
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37. Review: fish oils and lipid metabolism

Author

Harris, W.S.

Subjects
Fish oils -- Research -- Nutritional aspects, Lipid metabolism -- Research -- Nutritional aspects, Food/cooking/nutrition, Nutritional aspects, Research
Abstract

REVIEW: FISH OILS AND LIPID METABOLISM The possible hypolipidemic and antiatherogenic effects of fish oils were first considered in the 1970s, when epidemiological observations of Greenland Eskimos revealed an incidence [...]

Published
1989

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