Scientific reports

Trans fats: chasing a global ban - they have been repeatedly called the "low hanging fruit" in global prevention of cardiovascular disease. But will this month's New York health summit deliver the goods and help remove damaging trans fats from the world food chain? Rebecca Coombes reports for the British Medical Journal, 7 September 2011.
A mechanism by which dietary trans fats cause atherosclerosis - article in the Journal of Nutritional Biochemistry, e-published ahead of print on 30 October 2010. By Chen CL, Tetri LH, Neuschwander-Tetri BA, Huang SS, Huang JS, all Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine. "Dietary trans fats (TFs) have been causally linked to atherosclerosis, but the mechanism by which they cause the disease remains elusive. Suppressed transforming growth factor (TGF)-β responsiveness in aortic endothelium has been shown to play an important role in the pathogenesis of atherosclerosis in animals with hypercholesterolemia. We investigated the effects of a high TF diet on TGF-β responsiveness in aortic endothelium and integration of cholesterol in tissues. Here, we show that normal mice fed a high TF diet for 24 weeks exhibit atherosclerotic lesions and suppressed TGF-β responsiveness in aortic endothelium. The suppressed TGF-β responsiveness is evidenced by markedly reduced expression of TGF-β type I and II receptors and profoundly decreased levels of phosphorylated Smad2, an important TGF-β response indicator, in aortic endothelium. These mice exhibit greatly increased integration of cholesterol into tissue plasma membranes. These results suggest that dietary TFs cause atherosclerosis, at least in part, by suppressing TGF-β responsiveness. This effect is presumably mediated by the increased deposition of cholesterol into cellular plasma membranes in vascular tissue, as in hypercholesterolemia."
NICE recommends trans fat ban - the full story plus key extracts from the NICE document, links to news reports, documents, etc.
Food injurious to health - letter to the BMJ published 16 June 2010, arguing that there may already be a law against trans fats in food in the UK, in the UK Food Safety Act section 7.
Removing industrial trans fat from foods: a simple policy that will save lives - Editorial in the British Medical Journal. putting the case for a ban on trans fats as a simple, low cost, effective public health measure. By Dariush Mozaffarian, assistant professor of medicine and epidemiology, and Meir J Stampfer, professor of medicine and epidemiology, at Harvard Medical School and Harvard School of Public Health. Published in BMJ 2010;340:c1826, 15 April 2010.
A prospective study of dietary fat consumption and endometriosis risk - Stacey A. Missmer et al report in Human Reproduction Vol.00, No.0 pp.1-8, 2010 [doi:10.1093/humrep/deq044] on the strong negative association between fish oil consumption and endometriosis, and the the strong positive association with trans fat consumption. "Those women in the highest fifth of long-chain omega-3 fatty acid consumption were 22% less likely to be diagnosed with endometriosis compared with those with the lowest fifth of intake ... Those in the highest quintile of trans-unsaturated fat intake were 48% more likely to be diagnosed with endometriosis ... These data suggest that specific types of dietary fat are associated with the incidence of laparoscopically confirmed endometriosis, and that these relations may indicate modifiable risk. This evidence additionally provides another disease association that supports efforts to remove trans fat from hydrogenated oils from the food supply."
Stearic acid-rich interesterified fat and trans-rich fat raise the LDL/HDL ratio and plasma glucose relative to palm olein in humans by Kalyana Sundram, Tilakavati Karupaiah, Kc Hayes, Nutrition & Metabolism 2007, 4:3 (15 January 2007). This article raises interesting questions about the health impacts of stearic acid-rich randomly interesterified vegetable oil versus oleic-rich palm oil. The palm oil comes out best ... but then the study was funded by the palm oil industry. The study does not indicate where the difference arises, eg from the random arrangement of fatty acids in the triacyl glyceride, from the balance of monounsaturated to polyunsaturated fatty acids, or from the effects of palmitic versus stearic acid. We need answers to these questions before jumping to conclusions.
Trans fatty acids and coronary heart disease - editorial in the BMJ by Robert Clarke and Sarah Lewington of Oxford University, arguing for compulsory labelling of trans fats in food. Published on 29 July 2006, BMJ 2006;333:214.
BMJ editorial on trans fats - tfX responds. This is in response to the excellent article in the BMJ of 29 July 2006, "Trans fatty acids and coronary heart disease", in which Robert Clarke and Sarah Lewington of Oxford University call for the labelling of trans fat on product packaging. tfX argues that this alone is not enough - legal limits are also needed.
Trans Fat Diet Induces Insulin Resistance in Monkeys - by Kylie Kavanagh, Kate Jones, Janet Sawyer, Kathryn Kelly, Janice D. Wagner, Lawrence L. Rudel of the Wake Forest University School of Medicine, NC. Presented on 12 June 2006 at the 66th annual scientific sessions of the American Diabetes Association. Shows that monkeys fed on trans isomers of oleic acid gain weight relative to those eating cis, and that the weight is concentrated on the abdomen.
Higher Content of 18:1 Trans Fatty Acids in Subcutaneous Fat of Persons with Coronarographically Documented Atherosclerosis of the Coronary Arteries - by Dlouhy et al, Annals of Nutrition and Metabolism Vol. 47, No. 6, 2003. This paper shows that people with artheroscelerosis tend to have higher levels of 18:1 trans fatty acids in their fat, and concludes that "A higher concentration of 18:1 TFAs in the subcutaneous fat of patients with coronary disease might be an impulse to correct the dietary habits of this very high-risk population. "
Trans Fatty Acids and Cardiovascular Disease, by Dariush Mozaffarian, M.D. et al. Published in the New England Journal of Medicine, Volume 354:1601-1613 April 13, 2006 Number 15. An important review article summarising the serious damage to health caused by trans fatty acids. "On a per calorie basis, trans fats appear to increase the risk of CHD more than any other macronutrient, conferring a substantially increased risk at low levels of consumption (1 to 3 percent of total energy intake)."
Essential fatty acid isomers - a potential health risk? - by Ray Cook, investigates the world of differential toxicity of the various trans isomers of fatty acids. He concludes that the most hazardous are the trans polyunsaturates and especially the trans isomers of essential fatty acids, while trans isomers of monounsaturates may be almost or entirely harmless. This paper provides valuable insights into how trans fats might optimally be regulated, and indicates a higher than previously realised risk from the trans content of unhydrogenated liquid oils subjected to high temperature processing.
The case for not restricting saturated fat on a low carbohydrate diet by Jeff S. Volek and Cassandra E. Forsythe, Nutrition & Metabolism 2005, 2:21. "We believe that the recommendation to restrict saturated fat in favor of unsaturated fat on a low-carbohydrate diet is unnecessary and may even diminish some of the beneficial physiological effects associated with carbohydrate restriction." Short letter, followed by numerous useful references.
Dietary Fat Intake and Risk of Coronary Heart Disease in Women: 20 Years of Follow-up of the Nurses' Health Study - article in the American Journal of Epidemiology April 1, 2005; 161(7): 672 - 679, by Kyungwon Oh, Frank B. Hu, JoAnn E. Manson, Meir J. Stampfer and Walter C. Willett, based on a study of 78,778 women from 1980 onwards. "Findings continue to support an inverse relation between polyunsaturated fat intake and CHD risk, particularly among younger or overweight women. In addition, trans-fat intake was associated with increased risk of CHD, particularly for younger women."
Consumption of Trans Fatty Acids Is Related to Plasma Biomarkers of Inflammation and Endothelial Dysfunction - article in the Journal of Nutrition 135:562-566, March 2005, by Esther Lopez-Garcia et al, based on a study of 730 women. "Trans fatty acid intake has been associated with a higher risk of cardiovascular disease. The relation is explained only partially by the adverse effect of these fatty acids on the lipid profile. We examined whether trans fatty acid intake could also affect biomarkers of inflammation and endothelial dysfunction ... this study suggests that higher intake of trans fatty acids could adversely affect endothelial function, which might partially explain why the positive relation between trans fat and cardiovascular risk is greater than one would predict based solely on its adverse effects on lipids." By way of explanation we add that epithelial cells are those which line various bodily cavities including, with specific relevance to cardiovascular health, blood vessels.
Saturated fats: what dietary intake? by J. Bruce German and Cora J. Dillard, American Journal of Clinical Nutrition Vol. 80, No. 3, 550-559, September 2004. "At this time, research on how specific saturated fatty acids contribute to CAD and on the role each specific saturated fatty acid plays in other health outcomes is not sufficient to make global recommendations for all persons to remove saturated fats from their diet. No randomized clinical trials of low-fat diets or low-saturated fat diets of sufficient duration have been carried out; thus, there is a lack of knowledge of how low saturated fat intake can be without the risk of potentially deleterious health outcomes. "
Trans Fat Linked To Increase In Cholesterol - Pigs fed on a diet high in trans fats began to develop high cholesterol and arterial lesions after just two weeks. "These data suggest that a diet high in trans fat has the potential to promote the rapid development of cardiovascular disease in swine models." Paper presented at the American Physiological Society's "Experimental Biology" conference, April 17-21 2004, Washington, DC.
Dietary intake of trans fatty acids and systemic inflammation in women - paper in the American Journal of Clinical Nutrition, Vol. 79, No. 4, 606-612, April 2004, by Dariush Mozaffarian et al. "trans Fatty acid (TFA) intake predicts risks of coronary artery disease and diabetes. ... TFA intake is positively associated with markers of systemic inflammation in women. Further investigation of the influences of TFAs on inflammation and of implications for coronary disease, diabetes, and other conditions is warranted."
Dietary fat intake and 6-year cognitive change in an older biracial community population - a study of 2,560 participants of the Chicago Health and Aging Project, ages 65 and older, which finds that "higher intakes of saturated fat and trans-unsaturated fat were linearly associated with greater decline in cognitive score over 6 years". The trend was strongest for trans fat. Also, it was possible to maintain cognitive function by maintaining a dietary high ratio of unsaturated vegetable oil to saturated fat. From the Rush Institute for Healthy Aging, published in Neurology Vol. 62, 2004, pp.1573-1579.
Postprandial effects of dietary trans fatty acids on apolipoprotein(a) and cholesteryl ester transfer - paper in the American Journal of Clinical Nutrition, Vol. 77, No. 5, 1119-1124, May 2003, by Lissa M Gatto, David R Sullivan and Samir Samman. It finds that "The consumption of meals in which cis fatty acids (oleic acid) are replaced with trans fatty acids results in elevations in CET and in the formation of TRLs, which are relatively enriched in apo(a). The findings of the current study suggest that frequent ingestion of foods that contain TFAs has deleterious consequences on the composition of postprandial lipoprotein particles, which may enhance their atherogenicity.".
Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Paper in the American Journal of Clinical Nutrition, Vol. 77, No. 5, 1146-1155, May 2003, by Ronald P Mensink, Peter L Zock, Arnold DM Kester and Martijn B Katan. It concludes: "The replacement of trans fatty acids with unsaturated fatty acids from unhydrogenated oils is the single most effective measure for improving blood lipid profiles. Even small amounts of unsaturated fatty acids have a major effect on the ratio of total to HDL cholesterol. The efficacy of replacing SFAs with carbohydrates depends on the effects on body weight in the long term, and that effect is uncertain.".
High 18:2 Trans-Fatty Acids in Adipose Tissue Are Associated with Increased Risk of Nonfatal Acute Myocardial Infarction in Costa Rican Adults - by Baylin et al, published in J. Nutr. 133:1186-1191, April 2003. This study finds that "An association with 18:1 trans-FA was not detected. High 18:2 trans-FA in adipose tissue are associated with increased risk of MI. Because the use of hydrogenated oils is increasing worldwide, consumers should be aware of the harmful effects of products containing partially hydrogenated oils."
Essential Fatty Acids and the Brain - Marianne Haag of the Department of Physiology, University of Pretoria, South Africa reviews the role of essential fatty acids in brain membrane function and in the genesis of psychiatric disease. Published in The Canadian Journal of Psychiatry, April 2003.
Changes in the fatty acid composition of vegetable oils in model doughs submitted to conventional or microwave heating - this paper by Francesco Caponio, Antonella Pasqualone & Tommaso Gomes reports that heating unsaturated oils brings about a decline in their nutritional quality, especially by microwave. In particular, heating "caused an increase in the trans-isomers of unsaturated fatty acids and this was more evident after microwave treatment." Published in the International Journal of Food Science & Techonology Volume 38 Issue 4 Page 481 - April 2003.
Dietary Fats and the Risk of Incident Alzheimer Disease - report by Martha Clare Morris et al. which finds that intake of trans fats from hydrogenated oil correlates strongly with incidence of Alzheimer's disease. There is also a weaker correlation with intake of saturated fat. An inverse effect exists in the case of mono-unsaturated and omega-6 polyunsaturated oils. Published in Archives of Neurology Vol. 60 No. 2, 2003, pp.194-200.
Long-term intake of trans (n-3) polyunsaturated fatty acids reduces the b-wave amplitude of electroretinograms in rats. - by Acar et al. Published in the J. Nutr. Vol. 132, pp.3151-3154, October 2002. This study finds that "Dietary trans alpha-linolenic acid altered the fatty acid composition of retinal and hepatic phospholipids by significantly increasing the delta-19 trans-isomer of docosahexaenoic acid (DHA) ... We conclude that long-term intake of small amounts of trans-isomers of alpha-linolenic acid could disturb visual function."
Cholesterolaemic effect of palmitic acid in relation to other dietary fatty acids - this paper by Margaret French, Kalyana Sundram and M Thomas Clandinin shows that the effect of palmitic acid (a saturated fatty acid) at 10 percent of dietary energy in raising cholesterol is counteracted by linoleic acid (an omega-6 polyunsaturated fatty acid) at 4.5 percent of dietary energy. Conversely, "When the diet contained trans fatty acids plasma total and low-density lipoprotein-cholesterol increased and cholesterol synthesis increased with a decrease in high-density lipoprotein-cholesterol." Published in Asia Pacific Journal of Clinical Nutrition Volume 11 Issue s7 Page S401 - October 2002.
The Institute of Medicine (USA) Letter Report on Dietary Reference Intakes for Trans Fatty Acids. Written to the US Food and Drug Administration (FDA), this letter reports that there is no safe level of transfats in the human diet. It is one of the most definitive and hard-hitting reports on transfats and human health and an important weapon in the campaigners armoury. The full 33 page letter/report may be downloaded as a .pdf.
Cell Membrane Trans-Fatty Acids and the Risk of Primary Cardiac Arrest - by Lemaitre et al. Published in Circulation 2002, Vol. 105, p.697. This study finds that "Higher total trans-fatty acids in red blood cell membranes was associated with a modest increase in the risk of primary cardiac arrest after adjustment for medical and lifestyle risk factors. However, trans isomers of oleic acid were not associated with risk, whereas higher levels of trans isomers of linoleic acid were associated with 3-fold increase in risk ... "
Trans Fatty Acids: Properties, Benefits and Risks - a useful review article about trans fats and health by Masanori Semma of the Department of Health Sciences, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Japan. Published in the Journal of Health Science 48(1) 7-13, 2002.
Dietary fat intake and risk of type 2 diabetes in women - paper in the American J. of Clinical Nutrition, June 2001, by Jorge Salmerón et al. It finds a correlation with dietary trans fat and type 2 diabetes. "We estimated that replacing 2% of energy from trans fatty acids isoenergetically with polyunsaturated fat would lead to a 40% lower risk ... Substituting nonhydrogenated polyunsaturated fatty acids for trans fatty acids would likely reduce the risk of type 2 diabetes substantially."
Association between trans fatty acid intake and 10-year risk of coronary heart disease in the Zutphen Elderly Study: a prospective population-based study - Abstract of the Zutphen Elderly Study by Professor Daan Kromhout et al, as published in The Lancet. It concludes: "A high intake of trans fatty acids (all types of isomers) contributes to the risk of coronary heart disease. The substantial decrease in trans fatty acid intake, mainly due to industrial lowering of trans contents in Dutch edible fats, could therefore have had a large public-health impact."
Dietary trans alpha-linolenic acid from deodorised rapeseed oil and plasma lipids and lipoproteins in healthy men: the TransLinE Study. - by Vermunt et al, published in the British Journal of Nutrition March 2001, 85(3):387-92. This study of 88 men finds that "high trans alpha-linolenic acid diet significantly increased the plasma LDL-:HDL-cholesterol ratio by 8.1 % ... compared with the low-trans diet. This was largely explained by an increase in LDL-cholesterol on the high-trans diet, while no change was observed in the low-trans group ... In conclusion, trans alpha-linolenic acid may increase plasma LDL-:HDL-cholesterol and total cholesterol:HDL-cholesterol ratios."
Replacement of Dietary Saturated Fatty Acids by Trans Fatty Acids Lowers Serum HDL Cholesterol and Impairs Endothelial Function in Healthy Men and Women - article from Arteriosclerosis, Thrombosis, and Vascular Biology 2001;21:1233, by Nicole M. de Roos; Michiel L. Bots; Martijn B. Katan. This study of 29 volunteers compares the effects of saturated fats and trans fats on flow-mediated vasodilation (FMD), a risk marker of coronary heart disease (CHD). It concludes that "Consumption of TFAs resulted in lower HDL-C and a smaller FMD than consumption of saturated fatty acids. This might explain the increased risk of cardiovascular disease at high intakes of TFAs." (TFAs = trans fatty acids).
Genetic and Environmental Influences [on the development of allergy] - article in Allergy Volume 55 Issue 11 Page 1074, November 2000 by Innes Asher, Elif Dagli, Stephen T Holgate. Among the environmental causes of allergy is listed diet, and "especially trans fatty acids, margarine, maternal diet in pregnancy".
The effect of dietary trans-linolenic acid on plasma lipids and platelet fatty acid composition: the TransLinE study - by J. L. Sébédio et al, published in the European Journal of Clinical Nutrition February 2000, Vol. 54 No. 2, pp.104-113. This study found that "Dietary trans isomers of alpha-linolenic acid are incorporated in plasma lipids and converted to long-chain polyunsaturated fatty acids."
Incorporation and Metabolism of Dietary Trans Isomers of Linolenic Acid Alter the Fatty Acid Profile of Rat Tissues - by Loi et al, published in the Journal of Nutrition 2000 Vol.130 pp.2550-2555. "Geometrical isomers of alpha-linolenic acid representing 0.2 g/100 g of the experimental diet were incorporated into liver, platelets, aorta and heart, at the expense of their cis homologue and of 18:2(n-6) ... We conclude that 0.2 g of trans isomers of -linolenic acid per 100 g of diet was sufficient to be incorporated and metabolized, thus altering the fatty acid profile of rat tissues."
Dietary saturated fats and their food sources in relation to the risk of coronary heart disease in women - by Hu et al, published in the American Journal of Clinical Nutrition, Vol. 70, No. 6, 1001-1008, December 1999. An important study into the impacts on cardiovascular health of specific saturated fatty acids.
The Trans fatty acids report by the Harvard School of public health - .pdf download.
Trans fatty acids and coronary heart disease - a background and scientific review by the Harvard School of Public Health. "By our most conservative estimate, replacement of partially hydrogenated fat in the U.S. diet with natural unhydrogenated vegetable oils would prevent approximately 30,000 premature coronary deaths per year, and epidemiologic evidence suggests this number is closer to 100,000 premature deaths annually."
trans Fatty acids in human milk are inversely associated with concentrations of essential all-cis n-6 and n-3 fatty acids. Paper in the American J. of Clinical Nutrition by Sheila M Innis and D Janette King, September 1999. It finds that Canadian women produce milk whose fat content is on average 7.2% trans from dietary sources, with corresponding reductions in essential fatty acid content.
Effects of Different Forms of Dietary Hydrogenated Fats on Serum Lipoprotein Cholesterol Levels - report in the New England Journal of Medicine (Volume 340:1933-1940, June 24 1999, Number 25) by Alice H. Lichtenstein, D.Sc., Lynne M. Ausman, D.Sc., Susan M. Jalbert, M.L.T., and Ernst J. Schaefer, M.D. "Our findings indicate that the consumption of products that are low in trans fatty acids and saturated fat has beneficial effects on serum lipoprotein cholesterol levels."
High monounsaturated fatty acids intake protects against age-related cognitive decline. by Solfrizzi et al, in Neurology May 1999. Not actually about trans fatty acids, but supporting the fact that susceptibility to Alzheimer disease depends on fatty acid intake.
Desaturation and chain elongation of [1-14C]mono-trans isomers of linoleic and alpha-linolenic acids in perfused rat liver - by Lionel Bretillon et al, published in The Journal of Lipid Research Vol. 39, pp.2228-2236, November 1998. This study into the metabolic pathways of trans isomers of linoleic and alpha-linolenic acids shows that the geometry of the double bonds greatly affects metabolic conversion of the fatty acids.
Adipose tissue isomeric trans fatty acids and risk of myocardial infarction in nine countries: the EURAMIC study - by Aro et al, published in the Lancet 1995 Feb 4, Vol 345(8945):273-8. This study of 671 men with acute myocardial infarction indicates only a weak link between AMI and levels of 18:1 trans fatty acids in adipose tissue.
Trans fatty acid isomers in Canadian human milk. paper published in Lipids 1995 Jan;30(1):15-21, by Chen ZY, Pelletier G, Hollywood R, Ratnayake WM, of the Nutrition Research Division, Health Protection Branch, Health Canada, Ottawa, Ontario. This key paper finds that trans fat from dietary hydrogenated vegetable oil gets into human milk, on average at 7.2% of fat content among Canadian mothers, ranging up to over 17%. (Abstract only)
Trans-fatty acids intake and risk of myocardial infarction - by Ascherio et al, published in Circulation Vol. 89 1994, pp.94-101. This study of 239 patients in the Boston area shows that "intake of trans-fatty acids was directly related to risk of myocardial infarction ... Intake of margarine - the major source of trans-isomers - was significantly associated with risk of myocardial infarction." The 20% with the highest intake of TFA were 2.4 times more likely to suffer MI than the 20% with the lowest intake.
Nutritional Aspects of Cardiovascular Disease - Report of the Cardiovascular Review Group of the Committee of Medical Aspects of Food Policy number 46. Department of Health 1994, HMSO. As of 2004, this report is still the most recent official report in the UK that gives advice and recommendations on trans fats. It is also frequently quoted by the food industry, often in misleading ways. Hence we present these extracts from the report.
Trans-Fatty-Acid Content of Common Foods - letter to the New England Journal of Medicine (Volume 329:1969-1970, December 23 1993, Number 26). "The adverse effects of the trans fatty acids on the ratio of total cholesterol to high-density lipoprotein cholesterol is twice that of saturated fatty acids."
Preferential incorporation of dietary cis-9,cis-12,trans-15 18:3 acid into rat cardiolipins - by Wolff et al, published in Biochim Biophys Acta. 1993 Jul 1;1168(3):285-91. "Cardiolipins from mitochondria of different rat organs (heart; liver and kidney) appear to be privileged targets for the incorporation of cis-9,cis-12,trans-15 18:3 acid, a compound commonly found in deodorized edible linolenic acid-containing oils ... It is concluded that the trans-15 ethylenic bond is probably perceived as a single bond by enzymic systems that ensure acylation of cardiolipins."
Milk fat depression in C57Bl/6J mice consuming partially hydrogenated fat. - article in Journal of Nutrition 1990 Aug;120(8):818-24 by Teter BB, Sampugna J, Keeney M, of the Department of Chemistry and Biochemistry, University of Maryland, College Park 20742. The study finds that dietary trans fat reduces the amount of fat in the milk of mice.