Health and Well-being Science Review Trans Fatty Acids and risk of Coronary Heart Disease

Health and Well-being Science Review Trans Fatty Acids and risk of Coronary Heart Disease Trans fatty acids (TFA) are formed by natural biohydrogenation of fats in the rumen of cattle and sheep, i.e. ruminant TFA (rtfa). They can also be formed by partial hydrogenation of vegetable oils in industrial processing (itfa). The negative health impact of TFA was first discovered in the mid 1990 s, and there is now consistent evidence that industrial as well as ruminant TFA adversely affect the blood cholesterol profile. The impact of different dietary sources of trans fatty acids on coronary heart disease is still subject to controversy: most of the scientific evidence relates to industrial TFA and strongly shows a negative impact on CHD risk. Dietary intake of rtfa is generally not seen as a large health problem because intake is relatively low. However, the available data on rtfa indicate that the potential impact on CHD risk of equal intakes of ruminant and industrial TFA can be considered similar. Public Health authorities recommend limiting dietary intakes of TFA to below 1% of total dietary energy, because of their established adverse effects on heart health. In many countries, intakes of ruminant TFA are now higher than those of industrial TFA due to significant industrial reformulation. Public health measures and programmes to (further) reduce TFA intakes should focus both on further elimination of partial hydrogenation of vegetable fats and itfa, as well as reducing the intakes of saturated fats, which will also limit the intake of ruminant TFA. Authors: Peter Zock and Anne Wanders (Unilever R&D) Abbreviations TFA Trans fatty acid itfa Industrial Trans fatty acid rtfa Ruminant Trans fatty acid PHVO Partly Hydrogenated Vegetable Oil 95% CI 95 Percent Confidence Interval CHD Coronary Heart Disease En% Percent of total energy USLP Unilever Sustainable Living Plan SFA Saturated Fatty Acid CLA Conjugated Linoleic Acid PUFA Poly Unsaturated Fatty Acid MUFA Mono Unsaturated Fatty Acid

Review The main dietary sources of TFA are partially hydrogenated vegetable oil and ruminant fat There are two types of dietary trans fatty acids, referred to as industrial trans fatty acids ( itfa) and ruminant trans fatty acids (rtfa). Industrial TFA are mainly formed during partial hydrogenation of vegetable oil (PHVO). Only partially hydrogenated oils contain significant amounts of TFA, whereas fully hydrogenated oils, as applied in many virtually TFA-free products, only contain traces of TFA. The partial hydrogenation of vegetable oil results in a broad range of isomers of monounsaturated trans fatty acids (trans-c18:1), mainly C18:1n-7 (vaccenic acid), n-8, n-9 (elaidic acid) and n-10 and some trans isomers of linoleic acid (trans-c18:2). The TFA content in PHVO can range up to 50% of fatty acids, of which ca 80% trans-c18:1 and 20% trans-c18:2. Ruminant TFA are formed by natural hydrogenation of fats by bacteria in the rumen of cattle and sheep. Sources of rtfa are dairy products, beef and lamb meat. Ruminant TFA consist mainly of trans-c18:1, with C18:1 n-7, vaccenic acid as the predominant isomer. Ruminant fat also contains smaller amounts of trans-c16:1 and conjugated linoleic acid (CLA, cis,trans-c18:2), TFA s that are not found in PHVO. In ruminant fats, the TFA content ranges from about 2 to 5% of fatty acids, depending on the animals feed and the season of grazing. Health authorities advice to reduce the intake of TFA The Codex Alimentarius for regulatory and food labelling purposes defines TFA as All the geometrical isomers monounsaturated and polyunsaturated fatty acids having non-conjugated, interrupted by at least one methylene group, carbon-carbon double bonds in the trans-configuration (1). This means that by the Codex Alimentarius definition all types of itfa and rtfa, except CLA, are seen as trans fat. This is a point of debate, and the definition is not in all countries the same (2). For example, the Australia New Zealand Food Standards Code includes CLA in the definition (3), whereas the ban on trans fat in Denmark excludes rtfa. The World Health Organization recommends as part of the Global Monitoring Framework for Non- Communicable Diseases (NCD's) (4) to eliminate TFA from the diet and has called for national policies that virtually eliminate PHVO's in the food supply and replace these with polyunsaturated fatty acids (PUFA) (5). The FAO/WHO expert consultation on fats and fatty acids set an upper limit of 1 en% of TFA per day in 2008 (6). FAO/WHO advices reduction of TFA from PHVO via adaptations in the food industry and in legislation, but has put little emphasis on ruminant TFA. The recommendation of <1 en% TFA includes both ruminant TFA and industrial TFA for adults, but ruminant TFA is exempted from the <1 en% for infants and children up to 18 years (6). Other regional and local nutrition and health authorities have issued comparable recommendations on TFA. For example, EFSA concluded that TFA intake should be as low as possible (7), and the US Dietary Guidelines Advisory Committee recommends to avoid artificial (industrial) TFA (8). Page 2 of 8

Industrial as well as ruminant TFA s adversely affect blood cholesterol profile TFA lower HDL and TC/HDL ratio compared to carbohydrates and other fatty acids Controlled dietary intervention studies in humans have established the effects of TFA on blood cholesterol concentrations. TFA raise the level of LDL-cholesterol, lower HDL cholesterol, and as a consequence increase the ratio total to HDL-cholesterol (TC/HDL) in blood (9;10). TFA have adverse effects on the blood cholesterol risk profile for CHD as compared with carbohydrates and other dietary fatty acids, including SFA. The FAO/WHO expert consultation concluded that there is convincing evidence that TFA lower HDL and TC/HDL ratio compared to SFA, cis-mufa or PUFA (6). TFA from industrial and ruminant sources similarly affect HDL and TC/HDL ratio Over the years there has been some controversy about the impact of TFA from ruminant sources versus the impact of TFA from industrial sources. When in the early 1990s metabolic studies showed that consumption of industrial TFA raised LDL and lowered HDL cholesterol levels in the blood, it was suggested that the effect of different types of TFA on blood lipids may not be the same. However, intervention studies were lacking. In 2008, two intervention studies were published that directly investigated the effects on cholesterol profiles of diets containing ruminant TFA versus industrial TFA (11;12). Chardigny found that the TC/HDL cholesterol ratio was not significantly different between the diets. Yet, some differences between itfa and rtfa diets were found in HDL and LDL concentrations, and effects were more pronounced for women than for men (11). In the study by Motard-Bélanger both the itfa and the high dose rtfa (3.7 en%) increased the TC/HDL cholesterol ratio compared to the control diet low in TFA. A diet with a lower dose of rtfa (1.5 en%) did not have significant changes in the cholesterol profile as compared with the low TFA (0.8 en%) diet (12). A recent intervention study comparing a moderate dose rtfa (1.5 en%) with predominantly MUFA, showed a small, but significant decrease in HDL cholesterol concentrations with the rtfa diet (13). In 2010 and in 2013, Brouwer et al (14;15) summarized all published and unpublished studies on itfa and rtfa. For itfa they found that it increased LDL cholesterol by 0.048 mmol/l (95% CI 0.037 to 0.058) and it decreased HDL by -0.01 mmol/l (95% CI -0.013 to -0.007) for each 1 en% from industrial trans fatty acids replacing MUFA. For ruminant TFA they found that LDL increased by 0.045 mmol/l (95% CI -0.02 to 0.093) and HDL cholesterol decreased by -0.009 mmol/l (95% CI -0.025 to 0.007) for each 1 en% from rtfa replacing MUFA. The authors suggest that fatty acids with a double bond in the trans configuration unfavourably affect the blood cholesterol profile, regardless of whether they have been produced in factories or in the rumens of cattle and sheep. The unfavourable effects of rtfa were slightly less than those of itfa, although the difference between rtfa and itfa were not statistically significant. The 2010 US Dietary Guidelines Advisory Committee concluded that Limited evidence is available to support a substantial biological difference in the detrimental effects of industrial trans fatty acids (itfa) and ruminant trans fatty acids (rtfa) on health when rtfa is consumed at 7 to 10 times the normal level of consumption (8). In conclusion, research shows that industrial and ruminant trans fatty acids have at the same intake levels equally adverse effects on the blood cholesterol profile. Page 3 of 8

Although most evidence relates to industrial TFA, the potential impact on CHD risk of equal amounts of industrial and ruminant TFA can be considered similar TFA increase the risk of CHD events A number of prospective cohort and case-control studies have examined the relation between TFA intake and a risk of heart disease or TFA content of adipose tissue (a marker for TFA intake) and heart disease. Combined results of observational studies showed that risk increased with higher intakes of TFA (10). The FAO/WHO expert consultation concluded that there was 'convincing evidence' that TFA increase the risk of CHD events, and probable evidence exists for an increased risk of fatal CHD and sudden cardiac death (6). TFA from industrial and ruminant sources can be assumed to similarly affect CHD risk The results from epidemiological studies on possible differences between rtfa and itfa in their association with CHD risk are inconsistent. In 2011, a meta-analysis of prospective cohort studies was published on total TFA intake and CHD, as well as the intake specifically for TFA from both industrial and ruminant sources. The pooled analysis showed that the relative risk (RR) for CHD events of total TFA intake was 1.22 (95% CI: 1.08 1.38). For industrial TFA intake there was a trend towards a positive association (RR=1.21 (0.97 1.50)) and for ruminant TFA intake there was no significant association with risk of CHD (RR=0.92 (0.76 1.11)) (10;16). The studies on rtfa were studies with inverse associations, both significant (17) and non-significant (18), and with no associations (19;20) or weak, but non-significant positive associations (21). Recently, in their prospective population based cohort, Laake et al showed that intake of itfa from PHVO was associated with death from CHD. Moreover, they found that intake of rtfa increased the risk for death from CHD in women, but not in men (22). Possible reasons why rtfa is inconsistently linked with CHD in these epidemiological analyses include the relatively narrow range of rtfa intakes and the close link between rtfa and SFA in foods. The narrow range of rtfa intake as compared to the wide range of itfa intake in older cohorts, reduces the likelihood to detect an association with health outcome. Moreover, adjustment for SFA intake of associations between rtfa and CHD may underestimate (overcorrect) a true underlying relation. Thus, evidence on ruminant TFA and CHD endpoints in population studies is inconclusive. However, given that both ruminant and industrial TFA have adverse effects on the blood cholesterol risk profile, it is plausible and prudent to assume that ruminant TFA like industrial TFA increase the risk of CHD. In many countries intakes of ruminant TFA are higher than those of industrial TFA The major contributors to total TFA intakes are PHVO and ruminant fat. Before 1995, PHVO was the major source of TFA in Europe and North America. After the discovery that trans fatty acids have adverse effects on the blood cholesterol risk profile for CHD, TFA intakes have reduced. Strategies to limit TFA intakes are voluntary self-regulation; labelling and local or national bans (23). In other countries (e.g. India) measures to reduce TFA are not yet in place or effective (24;25). Page 4 of 8

Evidence from a number of countries indicates that the intake of TFA in the EU has decreased below the recommendation of <1 en% over recent years, owing to reformulation of food products, e.g. fat spreads, sweet bakery products and fast food (7). In France, intake data from 2008 show that TFA intakes are, on average, 1 en% in adults, including 0.6 en% for TFA from ruminant sources and 0.4 en% for TFA from other sources (26). In 2008-2009 in the UK, TFA provided on average 0.8 en%. Similar to France, in the UK the major contributors to TFA intake were meat and meat products, milk and milk products and cereal and cereal products (27). However, the decline of TFA in foods has been slower in Eastern European countries (28). In the United States TFA is required in food labeling from 2006 onwards. Additionally, in 2009, legislation to limit TFA in the food supply was enacted in several states by means of banning trans fats from retail food establishments or providing information about trans fats in menu items (29). There are no recent data on TFA intake in the US population available. Data from 1999-2002 indicate a TFA intake of 2.5 en%, of which the major sources were cakes, cookies, and pastries, as well as yeast breads, French fries, grains and ethnic dishes, and tortilla chips (30). New intake data are required to track changes in TFA intake as the result of the legislative mandates and food industry initiatives to decrease TFA in the food supply. In 2006, Food Standards Australia New Zealand (FSANZ) initiated a non-regulatory approach to reduce the level of TFA in the food supply. Since then, intakes of TFA of manufactured origin have declined in the Australian and New Zealand population by around 25-40%. In 2008-2009 Australians obtained on average 0.5 en% from TFA's and New Zealanders on average 0.6 en%, of which ruminant TFA contribute around 60 to 75% (3). In conclusion, as a result of the voluntary and legal changes in food composition, in many countries the intakes of TFA from ruminant sources are now higher than intakes from PHVO. Reducing the intakes of saturated fat will also limit the intake of ruminant TFA Intakes of ruminant TFA are not seen as a major health problem. As the intakes of rtfa are not high, they do not have a large impact on CHD risk in the population (31). Although on a gram per gram basis TFA are more detrimental than SFA (9), the intake of SFA is much higher, and therefore of more relevance for public health. Most important sources of rtfa are full-fat dairy products and beef and lamb meat. Along with a high content of rtfa, these products are also high in SFA, and on average are the main contributors to SFA intake in the population (27;32). At present, practical measures to reduce SFA intake focus on limiting the intake of full-fat dairy products and high-fat meats. Consequently, because SFA-rich products are also main sources of rtfa, limiting their consumption will also reduce intake of rtfa. To quantitatively illustrate this, if a person would consume the entire maximum recommended SFA intake (10 en% (6)) from ruminant food sources, rtfa intake is roughly 1 en%. In this calculation it is assumed that ruminant fats contain approximately 50% SFA and 5% rtfa. Because nonruminant food sources also significantly contribute to saturated fat intake in most diets, ruminant TFA consumption would be substantially lower than 1 en%, when adhering to a maximum of 10 en% SFA intake. Thus, from a public-health point of view, to reduce CHD the focus should be on replacing dietary SFA with PUFA, as it will also reduce rtfa intake. Page 5 of 8

Conclusion Industrial as well as ruminant TFA s adversely affect the blood cholesterol profile Although most evidence relates to industrial TFA, the potential impact on CHD risk of equal intakes of ruminant and industrial TFA can be considered similar. In many countries intakes of ruminant TFA are higher than those of industrial TFA Reducing the intakes of saturated fat will also limit the intake of ruminant TFA Key references 1. Codex Alimentarius. Guidelines on nutrition labelling. CAC/GL 2-1985. 2013. Codex International Food Standards. 2. Wang Y, Proctor SD. Current issues surrounding the definition of trans-fatty acids: implications for health, industry and food labels. British Journal of Nutrition 2013;in press:1-15. 3. Food Standards Australia New Zealand. Intakes of trans fatty acids in New Zealand and Australia: review report 2009. 2009. 4. World Health Organization. Global Strategy on Diet, Physical Activity and Health. 1-5-2004. 5. World Health Organization. A draft comprehensive global monitoring framework, including indicators, and a set of voluntary global targets for the prevention and control of noncommunicable diseases. 34-52. 31-10-2012. Geneva, World Health Organisation. 6. Foods and Agricultural Organization and World Health Organization. Fats and fatty acids in human nutrition. Report of an expert consultation. 91. 2010. 7. EFSA Panel on Dietetic Products NaAN. Scientific Opinion on Dietary Reference Values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol. EFSA Journal 2010;8:1461. 8. USDA. Report of the Dietary Guidelines Advisory Committee on the Dietary Guidelines for Americans. 14-6-2010. 9. Mensink RP, Zock PL, Kester ADM, Katan MB. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: A metaanalysis of 60 controlled trials. American Journal of Clinical Nutrition 2003;77:1146-55. 10. Mozaffarian D, Katan MB, Ascherio A, Stampfer MJ, Willett WC. Trans fatty acids and cardiovascular disease. New England Journal of Medicine 2006;354:1601-13. 11. Chardigny JM, Destaillats F, Malpuech-Brugere C et al. Do trans fatty acids from industrially produced sources and from natural sources have the same effect on cardiovascular disease risk Page 6 of 8

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