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Trans fatty acids - effects on systemic inflammation and endothelial function.

Consumption of trans fatty acids (TFA) predicts higher risk of coronary heart disease, sudden death, and possibly diabetes mellitus. These associations are greater than would be predicted by effects of TFA on serum lipoproteins alone. Systemic inflammation and endothelial dysfunction may be involved in the pathogenesis of atherosclerosis, acute coronary syndromes, sudden death, insulin resistance, dyslipidemia, and heart failure. Evidence from both observational and experimental studies indicates that TFA are pro-inflammatory. Limited evidence suggests that pro-inflammatory effects may be stronger for trans isomers of linoleic acid (trans-C18:2) and oleic acid (trans-C18:1), rather than of palmitoleic acid (trans-C16:1), but further study of potential isomer-specific effects is needed. TFA also appear to induce endothelial dysfunction. The mechanisms underlying these effects are not well-established, but may involve TFA incorporation into endothelial cell, monocyte/macrophage, or adipocyte cell membranes (affecting membrane signaling pathway relating to inflammation) or ligand-dependent effects on peroxisome proliferator-activated receptor (PPAR) or retinoid X receptor (RXR) pathways. Activation of inflammatory responses and endothelial dysfunction may represent important mediating pathways between TFA consumption and risk of coronary heart disease, sudden death, and diabetes. Further study is indicated to define these effects of TFA and the implications of such effects for cardiovascular health.

Atherosclerosis↗

Effects of trans fatty acids on lipid accumulation in 3T3-L1 cells.

Previous work had shown that dietary trans fatty acids (tFA) resulted in decreased fat deposition in adipose tissue. This study was conducted to see if tFA influence lipid accumulation in Swiss mouse fibroblast 3T3-L1 cells, which are widely used as an adipocyte model. Cells were cultured in the presence of experimental or control growth media supplemented with fatty acids complexed to bovine serum albumin. Fatty acid compositions of experimental and control growth media were similar except that the octadecenoates in the control growth media were cis fatty acids, whereas those in the experimental media contained both cis and trans fatty acids. Cell-conditioned media and cellular lipids at the preadipocyte and differentiating adipocyte stages were analyzed. At both stages of development, less fat accumulated in cells cultured in the presence of tFA, due primarily to a decrease in the nonpolar lipid content of cells exposed to tFA, and linoleate to arachidonate ratios were higher in cells supplemented with tFA. Calculations comparing sums of saturated and monounsaturated fatty acids in cells at the differentiating adipocyte stage suggested that tFA may have replaced monounsaturated fatty acids in the nonpolar lipid fraction and saturated fatty acids in the polar lipid fraction. The results of these studies are in good agreement with the in vivo effects of tFA seen in previous work with mouse adipose tissue. It was concluded that the 3T3-L1 in vitro model is an appropriate system for further studies of tFA and lipid metabolism in adipose tissue.

3T3 Cells↗

Trans fatty acids in hydrogenated fat inhibited the synthesis of the polyunsaturated fatty acids in the phospholipid of arterial cells.

Our hypothesis that the trans fatty acids in hydrogenated fat inhibited the synthesis of polyunsaturated fatty acids in the phospholipid of arterial cells was tested with five groups each with six pregnant porcine fed from d 35 of gestation and during lactation. The basal diet contained 2% corn oil (control). The other four diets included the control + 10% butter or 10% hydrogenated fat plus two levels of Mg. Plasma, milk and aortic phospholipid fatty acids, phospholipid composition and calcium content of the aorta from the piglets were determined. At 48 +/- 2 d of age, the aorta phospholipid of piglets from porcine fed hydrogenated fat contained a significantly higher concentration of linoleic acid, less arachidonic acid, and less long chain polyunsaturated fatty acid (PUFA) than did piglets from porcine fed either butterfat or the control diet. Mg had no effect. These changes in composition in piglets from porcine fed hydrogenated fat indicate that trans fat inhibits the metabolic conversion of linoleic acid to arachidonic acid and to other n-6 PUFA. The aortic calcium content data showed a significant interaction of calcium concentration with age. We concluded: 1) that dietary trans fat perturbed essential fatty acid (EFA) metabolism which led to changes in the phospholipid fatty acid composition in the aorta, the target tissue of atherogenesis, 2) this inhibition of EFA to PUFA by the isomeric fatty acids in hydrogenated fat is a risk factor in the development of coronary heart disease.

Age Factors↗

trans Fatty acids in milk produced by women in the United States.

BACKGROUND: trans Fatty acids (FAs) have been identified as negatively affecting human health. The trans FA composition of human milk fat must be examined to establish its influence on the nutritional quality of milk consumed by infants. OBJECTIVE: We sought to ascertain the individual and total trans FA isomers (sum of FAs containing at least one trans double bond) in human milk and to identify relations between individual FAs and milk fat concentration (% by wt). DESIGN: The FA composition of milk samples (n = 81) from women living in the southwestern United States was ascertained. The individual 18:1t isomers were separated. Correlations between each FA, total trans FAs, groups of similar FAs, and milk fat concentrations were examined. RESULTS: The mean total trans FA concentration was 7.0 +/- 2.3% (range: 2.5-13.8%). The concentration of total 18:1t was 5.1 +/- 2.0% (range: 1.5-11.6%), and Delta10t (range: Delta9-12t) was the most abundant isomer. CONCLUSIONS: Milk fat from women living in the United States contains concentrations of trans FAs similar to those in milk from Canadian women but greater than those reported in milk from women in other countries. In decreasing order of concentration, the Delta10t, Delta11t, Delta9t, and Delta12t isomers represented 78.9% of the total 18:1t. These FAs generally originate from partially hydrogenated vegetable oils and ruminant fat in the diet. No relation was found between the concentration of total trans FAs and milk fat concentration.

Adult↗

Quantitation of trans fatty acids in milk fat using spectroscopic and chromatographic methods.

Trans fatty acids (TFA) formed during biohydrogenation by ruminant animals were quantified in cows' milk fat by means of Fourier transform i.r. (FTIR) spectroscopy. When samples were analysed as the derived methyl esters, a spectral subtraction technique resulted in TFA values that were not biased by the unspecific absorption of intact triacylglycerols or influenced by the shape of the trans band. Austrian milk fat samples contained 20-50 g TFA/kg. Results obtained by analysis of TFA as triacylglycerols compared favourably with those obtained by using methyl esters. The findings of the FTIR method were further substantiated by applying argentation chromatography in combination with capillary gas chromatography to the same set of samples. Besides trans monoenoic acids, non-methylene interrupted cis, trans octadecadienoic acids contributed significantly to the total trans content. Two novel TFA, trans-11, cis-15 octadecadienoic and cis-9, trans-13 octadecadienoic acids, were identified in milk fat by means of their retention behaviour on argentation chromatography and gas chromatography as well as by an oxidative degradation procedure.

Animals↗

Dietary fat, trans fatty acids, and risk of coronary heart disease.

Results from human feeding studies and recent large-scale epidemiologic surveys suggest that dietary trans fatty acids enhance the risk of developing coronary heart diseases. Despite a lack of accurate data regarding dietary intake of trans fatty acids, existing epidemiologic data and evidence from experimental feeding studies support the idea that lowering current intakes of trans fatty acids may lower the risk of coronary heart disease.

Coronary Disease↗

Effect of sunflower, linseed and fish oils on the production of trans fatty acids in vitro.

In vitro anaerobic incubations were used to determine the effect of different oils (LO-linseed, SO-sunflower, FO-fish oil) on trans fatty acid production in rumen fluid and to test if combining of monensin (MON) with the oils affects the interactions on trans fatty acid concentrations in mixed cultures of ruminal microorganisms. Two different sources of rumen fluid were used; the inoculum from the sheep fed hay and barley (80:20%)--the inoculum A and the inoculum from the sheep fed alfalfa and barley (80:20 %)--the inoculum B. The analyses showed that inoculum B contained more short chain fatty acids (SCFA), medium chain fatty acids (MCFA) and saturated fatty acids (SFA) than inoculum A. In contrast, inoculum A contained more unsaturated fatty acids (UFA) than inoculum B. The results show, that the oils affected the biohydrogenation of fatty acids (FA) by increasing the concentration of C18:0 (3-7 times) and trans C18:1 isomers (2-9 times). The concentration of two main intermediates of FA biohydrogenation-- cis 9, trans 11 C18:2 (CLA) and trans 11C18:1 (TVA) were increased with the oils, but FO was more efficient than other plant oils on CLA and TVA production. The monensin treatment had similar effect on FA metabolism as the oil treatment in comparison to unincubated control. The interactions of monensin treatment with the oils were characterized with decrease (LO+MON, SO+MON) or increase (FO+MON) of the proportions of C18:0 and trans C18:1 isomers in comparison to oil treatment. The highest concentrations of two main isomers--CLA,TVA were found in the samples containing fish oil and monensin. In conclusion, fish oil treatment and monensin with fish oil treatment was more efficient than other plant oils in the effect on trans fatty acid production (mainly CLA and TVA) in fermentation fluid in vitro.

Animal Feed↗

Hyperlipidemic effects of trans fatty acids are accentuated by dietary cholesterol in gerbils.

Trans isomers of dietary fatty acids, generated during the commercial hydrogenation of unsaturated fats, may contribute to coronary heart disease (CHD) in humans by interfering with lipid metabolism. To examine this possibility in a fat-sensitive model, the Mongolian gerbil (Meriones unguiculatus) was used to compare the cholesterolemic and triglyceridemic potential of modest increments of trans fatty acids from partially hydrogenated soybean oil with other saturated fatty acids in the presence and absence of dietary cholesterol. Age-, dose-, and time-dependent effects were examined in weanling, 6-month-old, and 1-year-old gerbils. Although lipoprotein metabolism in weanling gerbils was initially refractory to trans fat, even as perturbations by saturated fatty acids were demonstrable, these gerbils eventually (after 16 weeks) developed a trans-induced hypercholesterolemia that was intermediate between the response to 16:0 and 12:0 + 14:0. The hepatic and plasma 18:1/18:2 cholesteryl ester (CE) ratio was depressed by trans in a manner similar to saturated fatty acids. The 6-month-old gerbils readily developed hypertriglyceridemia but not hypercholesterolemia, again revealing a decrease in the plasma 18:1/18:2 CE ratio. The 1-year-old gerbils revealed a dose-related (0, 5, 10%en as trans) elevation in total cholesterol (TC), and especially triglycerides (TG), that was accentuated by 0.04% dietary cholesterol. Increases in plasma lipids were again accompanied by a significant decrease in the mass of hepatic esterified cholesterol, particularly 18:1-cholesteryl esters. Thus, dietary trans-fatty acids induce age-, time-, and dose-dependent modulations in gerbil plasma lipids associated with decreased 18:1 cholesteryl esters. Further investigation with gerbils may reveal mechanisms by which trans fat consumption disturbs lipoprotein metabolism.

Journal Article↗

Biohydrogenation, duodenal flow, and intestinal digestibility of trans fatty acids and conjugated linoleic acids in response to dietary forage:concentrate ratio and linseed oil in dairy cows.

Duodenal flows of hydrogenation intermediates in response to changes in dietary forage:concentrate ratio (F:C) and linseed oil were evaluated using 4 lactating Holstein cows fed a low (65:35 forage to concentrate) or high (35:65) concentrate diet without (LC, HC) added oil or with linseed oil (LCO, HCO) at 3% of DM. A 4 x 4 Latin square design was implemented for 5 wk. Lower hydrogenation of 18:2n-6 and 18:3n-3 was observed with HC, but it increased with LCO or HCO. Duodenal flow of total conjugated linoleic acids (CLA) increased by 1.40 (LCO) to 3.01 (HCO) g/d with linseed oil. This response was associated with greater flows of cis9,trans11- (+0.21 to +0.55 g/d), trans11,cis13- (+0.33 to +0.36), trans11,trans13- (+1.01 to +1.15 g/d), and trans,trans-CLA (+0.12 to +0.72 g/d). Trans10,cis12-CLA flow averaged 0.08 g/d and was not affected by F:C or oil. trans11,cis15-18:2 flow increased by 8.5 (LCO) to 62 (HCO) g/d in response to linseed oil. Total trans-18:1 flow was 37 g/d in cows fed LC and increased to 81 g/d with HC. Feeding oil increased total trans-18:1 to the greatest extent with HCO. Flow of trans10-18:1 was lower with LC than with HC (1.46 vs. 20 g/d). Linseed oil increased trans11-18:1 flow by 40 (LCO) to 113 g/d (HCO). Feeding LCO and HCO also increased flows of trans6+7+8-, trans13+14-, trans15-, and trans16-18:1. Apparent intestinal digestibility of trans-18:1 isomers was largely unaffected by concentrate level and ranged between 67 and 95%. Linseed oil increased digestibility of nearly all isomers by 3 to 16 percentage units. Digestibility of cis9,trans11-CLA was greater in cows fed HC (55%) compared with cows fed LC (32%) and was not affected by linseed oil. Data suggest that high concentrate diets enhanced ruminal outflow of trans10-18:1. We provide initial in vivo evidence that supplemental 18:3n-3 is hydrogenated to trans11,cis15-18:2, trans11-18:1, trans13+14-18:1, trans15-18:1, trans6+7+8-18:1, and trans16-18:1 primarily.

Animals↗

Trans fatty acids and blood lipids.

Intake of trans-unsaturated fatty acids (TFA) has been consistently shown in multiple and rigorous randomized trials to have adverse effects on blood lipids, most notably on the LDL:HDL cholesterol ratio, which is a strong marker of cardiovascular risk. When a mixture of TFA isomers obtained by partial hydrogenation of vegetable oils is used to replace oleic acid, there is a dose-dependent increase in the LDL:HDL ratio. The relationship between amount of TFA as % of energy and the increase in the LDL:HDL ratio appears to be approximately linear, with no evidence of a threshold at low levels of intake, and with slope twice as steep as that observed by replacing oleic with saturated fats. The average impact of TFA induced changes in the LDL:HDL ratio correspond to tens of thousands premature deaths in the US alone. Although dramatic, this effect is substantially smaller than the increase in cardiovascular mortality associated with TFA intake in epidemiological studies, suggesting that other mechanisms are likely to contribute to the toxicity of TFA.

Cholesterol, HDL↗

The scientific basis for trans fatty acid regulations-is it sufficient? A European perspective.

The C18:1 trans fatty acids (TFA) comprise a variety of positional isomers, but no definite differences have been documented so far between the metabolic and health effects of industrial and ruminant TFA. In Europe the intake of industrially produced TFA (IP-TFA) has declined, and the majority of TFA are of ruminant origin. TFA have been replaced with cis-unsaturates in soft margarines and they have been reduced also in industrial fats, but often by using palm kernel oils. When modifying the dietary fat composition the proportion of saturated plus TFA should be kept to one-third of total dietary fatty acid intake.

Animals↗

Food labeling: trans fatty acids in nutrition labeling, nutrient content claims, and health claims. Final rule.

The Food and Drug Administration (FDA) is amending its regulations on nutrition labeling to require that trans fatty acids be declared in the nutrition label of conventional foods and dietary supplements on a separate line immediately under the line for the declaration of saturated fatty acids. This action responds, in part, to a citizen petition from the Center for Science in the Public Interest (CSPI). This rule is intended to provide information to assist consumers in maintaining healthy dietary practices. Those sections of the proposed rule pertaining to the definition of nutrient content claims for the "free" level of trans fatty acids and to limits on the amounts of trans fatty acids wherever saturated fatty acid limits are placed on nutrient content claims, health claims, and disclosure and disqualifying levels are being withdrawn. Further, the agency is withdrawing the proposed requirement to include a footnote stating: "Intake of trans fat should be as low as possible." Issues related to the possible use of a footnote statement in conjunction with the trans fat label declaration or in the context of certain nutrient content and health claims that contain messages about cholesterol-raising fats in the diet are now the subject of an advance notice of proposed rulemaking (ANPRM) which is published elsewhere in this issue of the Federal Register.

Community Participation↗

Effect of trans fatty acids on calcium influx into human arterial endothelial cells.

BACKGROUND: A recent task force of The American Society for Clinical Nutrition and American Society for Nutritional Sciences recommended in a position paper on trans fatty acids that models be developed to assess the effects of changes in fat intake on disease risk. OBJECTIVE: The objective was to investigate, using human arterial endothelial cells as a model, the influence of trans fatty acids and magnesium on cell membrane composition and on calcium influx into arterial cells, a hallmark of atherosclerosis. DESIGN: Endothelial cells were cultured for 3 d in media with high (adequate) or low (inadequate) amounts of magnesium plus various concentrations of trans,trans linoelaidic; cis,cis linoleic; trans elaidic; oleic; or stearic acids. The cells were then harvested and the fatty acid composition and the amount of (45)Ca(2+) incorporated into the cell was determined. RESULTS: The percentage of fatty acids incorporated into the endothelial cells was proportional to the amount added to the culture medium. Adequate magnesium was crucial in preventing calcium influx into endothelial cells. Without an adequate amount of magnesium in the culture medium, linoelaidic and elaidic acids, even at low concentrations, increased the incorporation of (45)Ca(2+) into the cells, whereas stearic acid and oleic acid did not (P < 0.05). CONCLUSION: Our model indicated that a diet inadequate in magnesium combined with trans fat may increase the risk of calcification of endothelial cells.

Calcium↗

Association between trans fatty acid intake and cardiovascular risk factors in Europe: the TRANSFAIR study.

BACKGROUND: High intakes of trans fatty acids (TFA) have been found to exert an undesirable effect on serum lipid profiles, and thus may increase the risk for cardiovascular disease. OBJECTIVES: Investigation of the association between TFA intake and serum lipids. DESIGN: Cross-sectional study in eight European countries (Finland, France, Greece, Iceland, The Netherlands, Portugal, Spain, Sweden) among 327 men and 299 women (50-65 y). Using a dietary history method, food consumption was assessed and TFA intake was calculated with recent figures on TFA levels of foods, collected in the TRANSFAIR study. RESULTS: Mean (+/-s.d.) TFA intake was 2.40+/-1.53 g/day for men and 1.98+/-1.49 g/day for women (0.87+/-0.48% and 0. 95+/-0.55% of energy, respectively), with the highest consumption in Iceland and the lowest in the Mediterranean countries. No associations were found between total TFA intake and LDL, HDL or LDL/HDL ratio after adjustment for cardiovascular risk factors. Additional adjustment for other fatty acid clusters resulted in a significant inverse trend between total TFA intake and total cholesterol (Ptrend<0.03). The most abundantly occurring TFA isomer, C18:1 t, contributed substantially to this inverse association. The TFA isomers C14:1 t9, C16:1 t9 and C22:1 t were not associated or were positively associated with LDL or total cholesterol. CONCLUSIONS: From this study we conclude that at the current European intake levels of trans fatty acids they are not associated with an unfavourable serum lipid profile. SPONSORSHIP: Unilever Research Laboratorium, the Dutch Dairy Foundation on Nutrition and Health, Cargill BV, the Institute of Food Research Norwich Laboratory, the Nutrition Branch of the Ministry of Agriculture, Fisheries and Food, the International Fishmeal and Oil Manufacturers' Association, Kraft Foods, NV Vandemoortele Coordination Center, Danone Group, McDonalds Deutschland Inc, Danish Veterinary and Food Administration, Valio Ltd, Raisio Group. European Journal of Clinical Nutrition (2000) 54, 126-135

Adipose Tissue↗

Energetic efficiency and mitochondrial function in rats fed trans fatty acids.

Nutritional experiments with growing rats were conducted to study the effect of dietary t18:1 and t,t18:2 in mixtures with safflower oil (77.1% linoleate) on oxidative phosphorylation of isolated liver mitochondria and on energetic efficiency as measured in energy balance experiments. Partially hydrogenated soybean oil (PHSO) with 45% t18:1 and an ethyl ester concentrate of trans fatty acids (TRANS) containing 52% t,t18:2 were used. Six groups of male rats were fed diets with 10% (wt/wt) fat supplements: 1, safflower oil (SAF); 2, 8% PHSO + 2% SAF; 3, 0.5% TRANS + 9.5% SAF; 4, 1% TRANS + 9% SAF; 5, 2% TRANS + 8% SAF; and 6, 5% TRANS + 5% SAF. These fat supplements contained 77.1, 17.1, 73.3, 69.4, 61.7 and 38% linoleate for groups 1-6, respectively. The basal metabolic rate was not affected by dietary treatments, neither were the metabolizable energy values. As compared to the SAF group, rats receiving the 8% PHSO + 2% SAF showed no different effect on energy utilization or mitochondrial respiratory function. TRANS was found to reduce the efficiency of metabolizable energy utilization at the 5% level (group 6), while mitochondrial ATP synthesis was significantly depressed in both the 2% and the 5% TRANS groups. A parallelism was observed between t,t18:2 incorporation in liver mitochondria, reduced mitochondrial oxidative function and depressed energetic efficiency. The experiments indicated that t,t18:2 exerted a significantly negative effect on energy utilization at 1.0 and 2.5% levels in the diet even when fed with relatively high concentrations of linoleate.

Adenosine Triphosphate↗

[Dietary trans-fatty acids: a risk factor for coronary disease].

Unsaturated fatty acids with their double bond in trans configuration raise serum low-density lipoprotein (LDL) cholesterol and lipoprotein(a) levels, and lower high-density lipoprotein (HDL) cholesterol in humans when substituted for cis unsaturated fatty acids in the diet. These effects should increase the risk of coronary heart disease, which is confirmed by epidemiological studies. Trans fatty acids are formed from cis unsaturated fatty acids during hydrogenation of vegetable oils in food industries. Until recently, major dietary sources of trans fatty acids in the Netherlands were frying fats, shortenings, and margarines, which in the past contained up to 50% of trans fatty acids. Nowadays, most shortenings and margarines sold in the Netherlands have a low trans fatty acid content due to manufacturing changes in the recent past. However, frying fats used in fast-food outlets still contain over 30% of trans fatty acids. French fries sold in these outlets provide 7-8 g of trans fatty acids per portion. Producers of frying fats for fast-food outlets therefore should also reduce the trans fatty acid content of their products as much as possible.

Cholesterol↗

Influence of diet on trans fatty acids in human milk.

In two experiments on relations between diet and milk lipids, subjects recorded food intake for 1 week and saved duplicate portions of foods consumed on 3 days. Diet collections were analyzed for selected nutrients and percent fatty acids. In the first experiment, for 1 week five subjects took morning and evening milk samples for fatty acid analysis. Significant differences were found in percentages of trans- 18:1 and total trans fatty acids between subjects' milks but not between morning and evening samples. In the second experiment six additional subjects collected milk samples in the morning only. Subjects were significantly different in the percentages of trans- 18:1 and total trans acids in their milks. In nine of the 11 subjects the fluctuation of percent total trans acids in the milk appeared to follow dietary trans changes after a 12 to 36 hr lag period. A significant correlation was found for diet and evening milk of the same day. Polyunsaturated/saturated ratios of the fatty acids in the diet lipids were related to those for milk lipids from the same evening and the next morning. Although other factors are involved, diet lipids influence trans fatty acids and polyunsaturated/saturated ratios of the fatty acids in human milk.

Adult↗

High 18:2 trans-fatty acids in adipose tissue are associated with increased risk of nonfatal acute myocardial infarction in costa rican adults.

Trans-fatty acid intake is associated with coronary heart disease (CHD), but the atherogenic potential of individual trans-fatty acids (FA) from partially hydrogenated oils (18:1 and 18:2) or meat and dairy products (16:1 and 18:1) is unclear. Incident cases (n = 482) of a first nonfatal myocardial infarction (MI) were matched with population controls (n = 482) for age, gender and area of residence, all living in Costa Rica. Trans-FA in adipose tissue samples were assessed by gas chromatography. Odds ratios (OR) and 95% confidence intervals were calculated from conditional logistic regression models. Total adipose tissue trans-fat was positively associated with risk of MI. After adjusting for established risk factors and other confounders, the OR by quintiles of total trans-fat were 1.00, 1.34, 2.05, 2.22 and 2.94 (P-test for trend < 0.01). This association was attributed mainly to 18:2 trans-FA that were abundant in both adipose tissue and in partially hydrogenated soybean oil, margarines and baked products used by this population; OR = 1.00, 0.96, 2.09, 3.51 and 5.05 (P-test for trend < 0.001). Adipose tissue 16:1 trans-FA were also associated with MI; OR = 1.00, 1.57, 1.39, 1.34 and 2.58 (P-test for trend < 0.05). 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.

Adipose Tissue↗