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Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73)

Published on Apr 12, 2016in BMJ 23.56
· DOI :10.1136/bmj.i1246
Christopher E. Ramsden16
Estimated H-index: 16
(UNC: University of North Carolina at Chapel Hill),
Daisy Zamora11
Estimated H-index: 11
(UNC: University of North Carolina at Chapel Hill)
+ 7 AuthorsJoseph R. Hibbeln46
Estimated H-index: 46
(NIH: National Institutes of Health)
Abstract
Objective  To examine the traditional diet-heart hypothesis through recovery and analysis of previously unpublished data from the Minnesota Coronary Experiment (MCE) and to put findings in the context of existing diet-heart randomized controlled trials through a systematic review and meta-analysis. Design  The MCE (1968-73) is a double blind randomized controlled trial designed to test whether replacement of saturated fat with vegetable oil rich in linoleic acid reduces coronary heart disease and death by lowering serum cholesterol. Recovered MCE unpublished documents and raw data were analyzed according to hypotheses prespecified by original investigators. Further, a systematic review and meta-analyses of randomized controlled trials that lowered serum cholesterol by providing vegetable oil rich in linoleic acid in place of saturated fat without confounding by concomitant interventions was conducted. Setting  One nursing home and six state mental hospitals in Minnesota, United States. Participants  Unpublished documents with completed analyses for the randomized cohort of 9423 women and men aged 20-97; longitudinal data on serum cholesterol for the 2355 participants exposed to the study diets for a year or more; 149 completed autopsy files. Interventions  Serum cholesterol lowering diet that replaced saturated fat with linoleic acid (from corn oil and corn oil polyunsaturated margarine). Control diet was high in saturated fat from animal fats, common margarines, and shortenings. Main outcome measures  Death from all causes; association between changes in serum cholesterol and death; and coronary atherosclerosis and myocardial infarcts detected at autopsy. Results  The intervention group had significant reduction in serum cholesterol compared with controls (mean change from baseline −13.8% v −1.0%; P Conclusions  Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes. Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid.
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References65
Newest
Published on Jan 1, 2016in Molecular Pain 3.21
Christopher E. Ramsden16
Estimated H-index: 16
(UNC: University of North Carolina at Chapel Hill),
Amit Ringel6
Estimated H-index: 6
(NIH: National Institutes of Health)
+ 9 AuthorsJ. M. Davis39
Estimated H-index: 39
(UIC: University of Illinois at Chicago)
BackgroundChronic idiopathic pain syndromes are major causes of personal suffering, disability, and societal expense. Dietary n-6 linoleic acid has increased markedly in modern industrialized populations over the past century. These high amounts of linoleic acid could hypothetically predispose to physical pain by increasing the production of pro-nociceptive linoleic acid-derived lipid autacoids and by interfering with the production of anti-nociceptive lipid autacoids derived from n-3 fatty acid...
14 Citations Source Cite
Published on Aug 1, 2015in The Journal of Pain 4.86
Christopher E. Ramsden16
Estimated H-index: 16
(UNC: University of North Carolina at Chapel Hill),
Daisy Zamora11
Estimated H-index: 11
(UNC: University of North Carolina at Chapel Hill)
+ 9 AuthorsAmber B. Courville16
Estimated H-index: 16
(NIH: National Institutes of Health)
Abstract Omega-3 and omega-6 fatty acids are biosynthetic precursors of endocannabinoids with antinociceptive, anxiolytic, and neurogenic properties. We recently reported that targeted dietary manipulation—increasing omega-3 fatty acids while reducing omega-6 linoleic acid (the H3-L6 intervention)—reduced headache pain and psychological distress among chronic headache patients. It is not yet known whether these clinical improvements were due to changes in endocannabinoids and related mediators d...
21 Citations Source Cite
Published on Jan 1, 2015in American Journal of Pathology 4.07
Huilin Liu2
Estimated H-index: 2
(University of Louisville),
Juliane I. Beier17
Estimated H-index: 17
(University of Louisville)
+ 4 AuthorsIrina A. Kirpich16
Estimated H-index: 16
(University of Louisville)
Experimental alcohol-induced liver injury is exacerbated by a high polyunsaturated fat diet rich in linoleic acid. We postulated that bioactive oxidized linoleic acid metabolites (OXLAMs) play a critical role in the development/progression of alcohol-mediated hepatic inflammation and injury. OXLAMs are endogenous ligands for transient receptor potential vanilloid 1 (TRPV1). Herein, we evaluated the role of signaling through TRPV1 in an experimental animal model of alcoholic liver disease (ALD). ...
10 Citations Source Cite
Published on Jan 1, 2015in Kennedy Institute of Ethics Journal 0.64
Kristof Van Assche4
Estimated H-index: 4
,
Laura Capitaine3
Estimated H-index: 3
+ 1 AuthorsSigrid Sterckx16
Estimated H-index: 16
Human body material removed post mortem is a particularly valuable resource for research. Considering the efforts that are currently being made to study the biochemical processes and possible genetic causes that underlie cancer and cardiovascular and neurodegenerative diseases, it is likely that this type of research will continue to gain in importance. However, post mortem procurement of human body material for research raises specific ethical concerns, more in particular with regard to the con...
3 Citations Source Cite
Published on Oct 28, 2014in Circulation 18.88
Maryam Sadat Farvid1
Estimated H-index: 1
(Shahid Beheshti University of Medical Sciences and Health Services),
Ming Ding10
Estimated H-index: 10
(Harvard University)
+ 5 AuthorsFrank B. Hu202
Estimated H-index: 202
(Harvard University)
Background—Previous studies on intake of linoleic acid (LA), the predominant n-6 fatty acid, and coronary heart disease (CHD) risk have generated inconsistent results. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the relation of dietary LA intake and CHD risk. Methods and Results—We searched MEDLINE and EMBASE databases through June 2013 for prospective cohort studies that reported the association between dietary LA and CHD ...
179 Citations Source Cite
Published on Oct 7, 2014in Circulation 18.88
Jason H.Y. Wu33
Estimated H-index: 33
(The George Institute for Global Health),
Rozenn N. Lemaitre2
Estimated H-index: 2
(UW: University of Washington)
+ 4 AuthorsDariush Mozaffarian113
Estimated H-index: 113
(Tufts University)
Background —While omega-6 polyunsaturated fatty acids(n-6 PUFA) have been recommended to reduce CHD, controversy remains about benefits vs. harms, including concerns over theorized pro-inflammatory effects of n-6 PUFA. We investigated associations of circulating n-6 PUFA including linoleic acid(LA, the major dietary PUFA), γ-linolenic acid(GLA), dihomo-γ-linolenic acid(DGLA), and arachidonic acid(AA),with total and cause-specific mortality in the Cardiovascular Health Study, a community-based US...
76 Citations Source Cite
Published on Jun 1, 2014in Current Opinion in Lipidology 3.85
Margaret R. Diffenderfer15
Estimated H-index: 15
,
Ernst J. Schaefer117
Estimated H-index: 117
Purpose of reviewDecreased size and increased density of LDL have been associated with increased coronary heart disease (CHD) risk. Elevated plasma concentrations of small dense LDL (sdLDL) correlate with high plasma triglycerides and low HDL cholesterol levels. This review highlights recent finding
62 Citations Source Cite
Published on Apr 1, 2014in Pflügers Archiv: European Journal of Physiology 2.77
Jean Chemin32
Estimated H-index: 32
(French Institute of Health and Medical Research),
Magali Cazade4
Estimated H-index: 4
(French Institute of Health and Medical Research),
Philippe Lory39
Estimated H-index: 39
(French Institute of Health and Medical Research)
T-type calcium channels (T-channels/CaV3) have unique biophysical properties allowing a calcium influx at resting membrane potential of most cells. T-channels are ubiquitously expressed in many tissues and contribute to low-threshold spikes and burst firing in central neurons as well as to pacemaker activities in cardiac cells. They also emerged as potential targets to treat cancer and hypertension. Regulation of these channels appears complex, and several studies have indicated that CaV3.1, CaV...
13 Citations Source Cite
Published on Mar 18, 2014in Annals of Internal Medicine 19.38
Rajiv Chowdhury47
Estimated H-index: 47
,
Samantha Warnakula9
Estimated H-index: 9
+ 11 AuthorsSimon G. Thompson95
Estimated H-index: 95
Primary Funding Source: British Heart Foundation, Medical Research Council, Cambridge National Institute for Health Research Biomedical Research Centre, and Gates Cambridge.
606 Citations Source Cite
Published on Jan 1, 2014in Circulation 18.88
Maryam S. Farvid27
Estimated H-index: 27
,
Ming Ding10
Estimated H-index: 10
+ 5 AuthorsFrank B. Hu202
Estimated H-index: 202
150 Citations Source Cite
Cited By114
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Published on Mar 14, 2019in BMC Medicine 9.09
Jie V. Zhao2
Estimated H-index: 2
(HKU: University of Hong Kong),
C. Mary Schooling20
Estimated H-index: 20
(CUNY: City University of New York)
Background The role of n-6 polyunsaturated fatty acids (PUFAs) in ischemic heart disease (IHD) is controversial, and dietary guidelines vary. Observationally, lower saturated fat intake and higher intake of vegetable oils rich in linoleic acid (LA), the main n-6 PUFA, is associated with lower IHD and diabetes; however, randomized controlled trials have not fully corroborated these benefits. We assessed how genetically predicted LA affected IHD and its risk factors, including diabetes, lipids, an...
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Published on May 4, 2019in Obesity science & practice
S. Ghosh (UPenn: University of Pennsylvania), J. F. O'Connell (NIH: National Institutes of Health)+ 5 AuthorsJosephine M. Egan63
Estimated H-index: 63
(NIH: National Institutes of Health)
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Published on Jun 1, 2019in Medical Hypotheses 1.12
Richard D. Semba65
Estimated H-index: 65
,
Ruin Moaddel30
Estimated H-index: 30
+ 2 AuthorsLuigi Ferruci142
Estimated H-index: 142
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Published on May 16, 2019in Nature Reviews Cardiology 15.16
Jason H.Y. Wu33
Estimated H-index: 33
(The George Institute for Global Health),
Renata Micha37
Estimated H-index: 37
(Tufts University),
Dariush Mozaffarian113
Estimated H-index: 113
(Tufts University)
The effect of dietary fats on cardiometabolic diseases, including cardiovascular diseases and type 2 diabetes mellitus, has generated tremendous interest. Many earlier investigations focused on total fat and conventional fat classes (such as saturated and unsaturated fats) and their influence on a limited number of risk factors. However, dietary fats comprise heterogeneous molecules with diverse structures, and growing research in the past two decades supports correspondingly complex health effe...
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Published on May 1, 2019in Food and Chemical Toxicology 3.98
Ruijie Liu10
Estimated H-index: 10
(University of Texas at Austin),
Min Cheng (Jiangnan University)+ 6 AuthorsJ. Thomas Brenna36
Estimated H-index: 36
(University of Texas at Austin)
Abstract Despite its 50-year history, the conventional diet-heart hypothesis holding that dietary saturated fats raise serum cholesterol, and with it, cardiovascular risk, remains controversial. Harsh chemical and physical treatment generates process contaminants, and refined oils raise serum and tissue cholesterol in vivo independent of saturated fat content. We developed an in vitro bioassay for rapidly assessing the influence of oils on cholesterol metabolism in the human liver HepG2 cell lin...
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