Significance Of Vitamin E In Regulation Of Cholesterol Level And Its Associated Diseases

Navita Bansal, Vinutha T and Shelly Praveen, Division of Biochemistry, IARI, Pusa, New Delhi-110012

2019-04-11 08:53:39

Figure 1 Credit: Navita Bansal

Figure 1 Credit: Navita Bansal

Antioxidants play a major role in preventing free radicals generated oxidative damage which is the basis of many diseases including cancer, cardiovascular diseases, loss of memory, eye diseases and aging . There are lots of natural and synthetic antioxidants available  but vitamin – E (vit-E) is the major and potential natural antioxidant that prevents oxidative damage  by scavenging free radicals and hence limits or delays  the harmful effect of them on our body. Apart from antioxidativerole ,vit-E has been found to possess many other biological activities including  anti-inflammatory, anti-obesity,  anti-hyperglycemic, anti-hypertensive and anti-hypercholesterolemic. Vit-E is a fat soluble vitamin composed of a total of 8 subtypes (four isoforms of each of  tocopherols and tocotrienols viz. α-, β-, γ-, and δ- ). In general 15 mg of vitamin E is sufficient for adults to meet the daily requirement and its daily requirement differs according to the gender and the age  and it can be easily obtained naturally from vegetables oils, wheat germ oil, olives and nuts.

Although Vitamin E has many potential functions in preventing nutrient related diseases or disorders but general public is little aware about its importance.Morever, due to poor life style, pollution and unhealthy eating habits we are at increased risk of developing nutrition related diseases like obesity, cardiovascular diseases, diabetes and many more . Insufficient plasma αTF (α- tocopherol) level ( <12 μmol/L) in human can lead to multiple health complications including increased infection, anemia, growth impairment ,  unhealthy infant and mother during pregnancy (Traber, 2014). Other reports suggest that a plasma α –tocopherol concentration of 30 µmol/L is sufficient to prevent many nutrition related diseases (Raederstorff D et al ,2015).

Vitamin  E role in cholesterol regulation and its mechanism of regulation

Various studies has suggested that oxidative stress is the fundamental cause of   many diseases and metabolic disorders like obesity, cardiovascular diseases, hypercholesterolemia, hyperglycemia etc..Problem of obesity and hypercholesterolemia has increased in children as well as in adults worldwide. Cholesterol is an integral component of mammalian cell membranes and plays essential role in maintaining cell membrane integrity, cell signaling processes and is necessary for cell growth.  Cholesterol is carried in a conjugated form via lipoproteins through bloodstream . There are majorly three forms of lipoproteins LDL (low density lipoproteins/bad cholesterol), HDL (high density lipoproteins/good cholesterol) and VLDL (very low density lipoproteins). It is observed that higher level of LDL increases the risk of obesity and cardiovascular diseases. Higher LDL level results in cholesterol deposition along the inside of blood vessels forming a hard substance called cholesterol plaque that narrow the blood vessels and hence causes impaired blood flow. Oxidative stress causes oxidation of LDL molecule which causes modification in both lipids (fatty acid and lipids oxidation generating esterified and aldehyde form of fatty acids e.g. malondialdehyde which is the aldehyde form of fatty acids)  and protein moieties (modification of amino acids, proteolysis, apoprotein B crosslinking; Fong LG , 1987) present in LDL. Exposure of LDL particle to oxidizing agents (superoxide anion and hydrogen peroxide present in cells, especially macrophages present in the arterial wall), enzymes like lipoxygenases and peroxidases and products generated by myeloperoxidase results in formation of oxidized LDL (oxLDL).  Vitamin E plays an important role in maintaining and regulating cholesterol and LDL level  by mainly two mechanisms by  inhibiting LDL oxidation and by suppressing the activity of HMG-CoA reductase enzyme (fig 2).  Normally LDL is internalized by the specific LDL receptor present on the cell but any modification in the LDL receptor or LDL molecule can lead to the loss of recognition between LDL receptor and LDL leading to high plasma cholesterol and LDL level and hence can cause cardiovascular diseases such as atherosclerosis (narrowing of the arteries) (fig. 2).  Various studies showed that modification of LDL particle makes it susceptible for oxidation and this oxidation is  inhibited by vit-E.Vit-E in LDL particles prevents lipid peroxidation and protein modification in LDL  by reactive oxygen species (ROS) by acting as a chain-breaking antioxidant. Each LDL particle  can carry app. 12 vit-E molecules on an average  and  protect the oxidation of LDL molecule. Transportation of vit- E in blood shares the cholesterol and lipoprotein pathways as there is no specific plasma protein for its transport. Hence the transport of lipoproteins toward the liver facilitates the delivery of hepatic vit- E. Extrahepatic tissues can receive vit -E  through very low-density lipoprotein (VLDL)/LDL uptake via specific receptors or from the LPL (lipoprotein lipase which catalyzes the breakdown of triglycerides) product  (Schmolz L, 2016). Another mechanism of lowering cholesterol/LDL level involves the inhibition of enzyme 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase which catalyzes the major rate limiting step in the biosynthesis of cholesterol. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate which is a necessary step involved in cholesterol synthesis pathway. Studies shows that tocotrienols (mainly γ- and δ- ) apart from tocopherols significantly suppress the   3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity due to their unsaturated side chains resulting in less cholesterol synthesis by the liver cells ( Ricciarelli R ,1999).

Obesity : cause behind hypertension,hyperglycemia and its control

Higher levels of LDL and cholesterol is also associated with another major health problem, obesity. Consumption of high fat diet is the major reason behind obesity. Obesity is considered to be the main cause behind other many metabolic disorders and diseases which includes insulin resistance, hypertension, sleep disorder and dyslipidemia . Some reports showed that obesity in adolescents is associated with high levels of LDL (-ve) (electronegative LDL which is the subfraction of modified form/oxidized form of LDL) and low levels of α- tocopherol. Also, changes in number and size of adipose tissues has been observed during obesity. Vitamin E supplementation in obese mice decreased oxidative stress and reduced collagen deposition in the VAT (visceral adipose tissue) of obese mice given vitamin E supplementation allowing a further expansion of the adipocytes and increasing the storage capability, reducing the  lipotoxic effects associated with obesity(Alcaca M, 2015.) (fig. 3). Zhao L et al (2015) demonstrated that γ-tocotrienol improves high-fat diet-mediated obesity by preventing systemic and adipose inflammation and by counteracting pro-inflammatory cytokines. Hence, circulating oxidized LDL and electronegative LDL is considered as a marker of oxidative stress and its increased level can be associated with obesity, cardiovascular diseases, metabolic syndromes and insulin resistance in adults. In addition to this, determination of Vitamin E: cholesterol ratio can be used to identify the patients with increased risk of high LDL level and hence risk of heart diseases .

Considering the high impact of vit- E and its role in preventing the nutrient related diseases and disorders, vit- E supplementation or consumption of vitamin E rich diet would be an appropriate strategy to help in treatment or the prevention of obesity, higher cholesterol level, hyprglycemia and its associated diseases like cardiovascular diseases.


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