Trans-Fats
Trans fatty acids are unsaturated fatty acids that have at least one double bond in the chemical structure. Trans fatty acids are chemically different than other fatty acids because their chemical structure is trans rather than a cis configuration. Cis configuration is a geometric isomer where the hydrogen bond is bent so the carbon molecules are on the same side of the bond and trans configuration has the carbon branching on the opposite sides of the double bond.
There are two types of trans fatty acids, one is created naturally through stomach ruminant trans fatty acid and the other is artificially created through a chemical process called hydrogenation. Ruminant TFA Partially hydrogenated trans fats are formulated through the chemical process of changing the structural backbone of polyunsaturated bonds by breaking a double bond and adding hydrogens as a replacement to the carbon molecule that was left from the breaking of the double bond (Mensink). The most common trans-fat used in the human diet are elaidic acids which have eighteen carbons and one trans double bond (Mensink). The trans fat found naturally are created from bacteria that cause fermentation in the ruminant stomach of cows or sheep. The ruminant trans fatty acids are then incorporated into the human diet through dairy and meat intake (Mozaffarian).
Hydrogenation was first developed in the 1890’s by Nobel laureate Paul Sabatier but chemist Willhelm Normann proved in 1901 how to actually facilitate the hydrogenation of liquid oils such as vegetable oils and patented the process (wiki). In 1911 Crisco became the first such product marketed in the United States (Angell). Partially hydrogenated vegetable oils became increasingly appealing to the food market and industry because of how the chemical trans structure modified the products into semisolid fats. In a trans geometric configuration it creates a more condensed and rigid conformation. The rigidity of partially hydrogenated products changes the melting point because the bonds are harder to break at room temperature, the more trans-fats created in the hydrogenation then the more solid the product will be. Processed vegetable oils started to replace animal fats because they were more shelf-stable, palatable in baking and cooking, and economical. In the 1970’s margarine which is made from partially hydrogenated oil was marketed as healthier than alternative butter because so little research had been initiated on effects of hydrogenation (Angel).
Today studies of trans fatty acids have been associated with increased risks for the cardiovascular disease and coronary heart disease. Cardiovascular disease (CVD) is a general term that refers to abnormal conditions that create dysfunction with the heart and blood vessels. The Centers for Disease Control and Prevention website states approximately 600,000 people die annually from heart disease in the United States (CDC). Coronary Heart Disease (CHD) is a type of cardiovascular disease that occurs when coronary arteries become blocked or constricted due to plaque deposits that restrict oxygen and nutrient flow to the heart itself, which can lead to a heart attack (nut book). Coronary Heart Disease is the most prevalent type of CVD and claims the lives of about 385,000 people a year in the United States alone (CDC website).
When trans fats were first established through partially hydrogenated unsaturated fats the physical effects on the human body were not of concern medically at that point in time. Today studies have shown numerous adverse effects that cause a direct link to an increased risk for coronary heart disease. Several studies now link trans-fats to raising low-density lipoprotein cholesterol levels (LDL), lower high-density lipoprotein cholesterol (HDL), increase lipoprotein levels, raise plasma triglyceride levels, adversely affect essential fatty acid metabolism and prostaglandin balance, promote inflammation, and lastly cause endothelial dysfunction (Ahsan, Mozzafarian,Mensnik).
Low-density lipoprotein cholesterol levels are shown to increase in higher trans-fat diets. LDLs are not as dense as HDLs because they carry a higher percentage of cholesterol in the lipoprotein matrix. The more LDLs circulating in the blood decreases the uptake of the cholesterol to cells in the body. When the LDLs are not taken up by body cells they begin to degrade over time releasing cholesterol directly into the blood. Cholesterol in the blood stream can facilitate itself into the walls of blood vessels and create atherosclerosis or basically plaque formation and increases the risk for cardiovascular disease like CHD.
Trans fatty acids are the only fatty acids that studies have shown to truly decrease levels of high-density lipid proteins. HDL cholesterols are very dense and small with low cholesterol content and high protein content. Their main function is to pick up the cholesterol from dying cells and arterial plaques and transfer them to other lipoproteins which then are taken up by the liver. The liver then takes the cholesterol and uses it synthesize bile and removes it from the circulatory system. Therefore, if trans-fats reduce HDL levels then more cholesterol is left in the body creating more plaque buildup and increasing atherosclerosis which increases the risk for CHD.
The increase of atherogenic lipoprotein (a) levels is a direct correlation to CVD. Lipoprotein (a) is a risk factor for plaque thrombosis which is blood clot that can detach and become immobilized in a smaller more restricted artery such as coronary arteries (Barbier). Basically the higher the levels of lipoprotein (a) the more accumulation of plaque buildup within vessel walls by inhibiting plasminogen and the result is fibrin left to increase clotting of the arteries (Caplice).
The increase in triglyceride levels due to higher trans-fat diets equals a lower rate at which the liver can emulsify the lipids out of circulation. Chylomicrons are what hold triglycerides in a phospholipid layer and carry them into the blood for cell absorption. If the blood is overwhelmed with triglyceride levels then more deposits will be left within the body to degrade and increase the rate of CHD. Trans fatty acids influence fatty acid metabolism of adipocytes which reduce triglyceride uptake and reduced esterification of newly synthesized cholesterol will lead to the increase in production of free fatty acids (Mozzafarian). Trans fat basically alters the expression in adipocytes of genes for peroxisome-proliferator-activated receptor-y (PPARs), resistin, and lipoprotein lipase (mozzafarian). Lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of triglycerides found in lipoproteins, chylomicrons, and very low-density lipoproteins (VLDL) (Nut book). If lipoprotein lipase is compromised then it will increase blood triglyceride levels due to lack of absorption in adipose cells. Resistin is a hormone that has been shown to increase the level of LDL in arteries which creates a higher risk for cardiovascular disease (Lazar).
Prostaglandin balance is what regulates the vascular constriction of smooth muscle and is derived from arachodonic acid. Trans fatty acids affect prostaglandin balance by inhibiting the enzyme delta-6-desaturase which can promote thrombogensis (Frank). Thrombogenesis as discussed earlier is the formation of a blood clot in arteries that can lead to myocardial infractions of the heart and lead to further risk of coronary heart disease and cardiovascular disease.
Systemic inflammation is also increased due to trans fat diets. The inflammation can be seen by the increased activity of the tumor necrosis factor (TNF) system and increased levels of interleukin-6 and C-reactive protein (Mozzafarian). TNF-a and cytokines such as interleukin-6 are what promote inflammation from adipocytes. The problem with increased inflammation is that it causes plaque to crack. When plaque cracks it clumps together because of the sticky nature of fibrin clotting formation that is found in platelets (Dormer). C-reactive protein and interleukin-6 levels in blood are a way to test for inflammation which can lead to atherosclerosis. The inflammatory effects of trans fats and the difference in the level of C-reactive protein was shown through a median intake of 2.1 percent as compared with 0.9 percent of total energy in a study of women with higher body-mass indexes and a greater intake of trans fatty acids (Mozaffarian). This median intake could relate to an increase risk of CVD by thirty percent. The activation of cells in atherosclerotic lesions is what releases pro-inflammatory molecules. TNF and cytokines stimulates the TNF (a) receptor which is another indicator of inflammatory processes (Mozzafarian).
In 2004 a study was done to determine the effect of trans fatty acid diets in relation to endothelial dysfunction and an increase to cardiovascular disease by Lopez-Garcia et al. Endothelial dysfunction is indicated by altered vasodilation and increased production of inflammatory molecules. This study was to gain perspective on whether endothelial function was adversely affected by higher concentrations of trans fatty and relate the increased risk for cardiovascular risk when compared to other lipid diets (Garcia). The study examined plasma concentration of inflammation and endothelial dysfunction by measuring C-reactive protein, interleukin-6, soluble intercellular and vascular cell adhesion molecules in healthy women from female registered nurses in the US. The study ended up showing that all of the plasma concentration levels were increased regardless of the women’s BMI being leaner or heavier. Women in the higher quintile of BMI had their C-reactive protein increased by 73% and women in the lowest quintile had an increase of 17 percent (Lopez). C-reactive protein levels are a significant sign of inflammation which is a precursor to CHD. The study presented a new reason why trans-fats have a higher association with CVD rather than looking only at blood lipid levels. E-selection, sICAM-1, and sVcam-1 are surface soluble cell adhesion molecules that tend to be overexpressed when the endothelium encounters inflammatory stimuli such as with C-reactive protein and TNF (a) (Garcia). All of the soluble cell adhesion molecules are directly predictors to atherosclerosis, myocardial infractions, or coronary heart disease. The idea is that trans fats are somehow incorporated into endothelial cell membranes and further alter cellular and macromolecular components acting at the interface of the blood vessel wall (Garcia).
Fatty acids mediate cell function by use of the phospholipids in cellular membranes. They also bind to and change nuclear receptors of gene transcription like peroxisome-proliferator-activated receptors (PPAR). PPARs can repress gene transcription and have a direct effect on atherogenesis (Barbier). They also control plasma levels of cholesterol and triglycerides, which constitute major risk factors for CHD. Trans fatty acids increase free fatty acids within the plasma and if PPARs are inhibited then fatty acid uptake in the mitochondria cannot take place. In mice that had no PPARa massive cardiac and hepatic lipid accumulation and hypoglycemia were observed (Barbier). One trial study showed that elaidic acid consumption decreased expression of PPARy which would accelerate the risk of cardiovascular disease. The study took murine macrophage RAW264.7 cells and treated them with 0.5, 1, and 2mM concentrations of elaidic acid for six hours and the control group was treated with fifty percent eathanol. The results showed that elaidic acid decreased PPARy gene expression in RAW264.7 macrophage cell line by -1.36, -1.68, and -3.24 times compared to the control group (Yegane). This study shows that trans fatty acids inhibit PPARy gene expression and reduce the uptake of triglyceride and LDL and increase the risk for cardiovascular disease.