Bowling Green State University Jessica Moosbrugger VITAMIN E: TOCOPHEROLS AND TOCOTRIENOLS

Table of Contents Introduction....1 Background.....1 Tocotrienols.....2 Vitamin E Structures.......2 Metabolic Pathway..3 Availability......3 Natural Form4 Synthetic Form.4 Recommended Dietary Allowance..5 Toxicity5 Deficiency6 Benefits7 Cardiovascular Disease7 Cancer..8 Cognitive Functions.8 Conclusion...8

Introduction Adequate nutrient intake is a major contributor for optimal human health. Many vitamins and minerals have been discovered over the years, each with specific functions that can maintain or improve human health. The vitamins in the diet consist of either fat-soluble vitamins or watersoluble vitamins. The main difference between these two types of vitamins is that, when ingested, water-soluble vitamins are not absorbed into the body, whereas fat-soluble vitamins are. Fat-soluble vitamins are soluble in lipids therefore, when they are ingested, the body uses what it needs at that time and the rest is then stored in the fat tissues of the body. This process makes it possible for the body to use the remaining product at another time when it is necessary. The four main types of fat-soluble vitamins include vitamin A, vitamin D, vitamin E, and vitamin K.

All of the fat-soluble vitamins are vital to human health and serve many functions in the human body. Vitamin E, particularly, is a nutrient that is most commonly known for its antioxidant properties. The two types of vitamin E are tocopherols and tocotrienols and they are each available in four different forms. Of the eight different forms of tocopherol and tocotrienol, alpha-tocopherol is the most preferred form and is found mainly in plant products. Not only is vitamin E a powerful antioxidant, but it provides exceptional immune function as well (5). These properties, along with many others, make vitamin E especially essential and beneficial to human health, disease prevention and disease treatment.

Background For many years, vitamin E has been a well-known and vital nutrient to human health. Tocopherols were discovered in 1922 by Herbert Evans and Katherine Bishop while performing studies on the reproduction of rats. Further studies by Henry Mattill and Harold Olcott concluded that there are many rich antioxidant properties that vitamin E is composed of (5). Tocopherols are considered to have the highest amount of biological potency, so they are used as a standard when being compared to other forms (3). There are a total of eight different forms of vitamin E discovered in nutrition. These forms include alpha-, beta-, gamma-, and delta tocopherols and alpha-, beta-, gamma-, and delta tocotrienols.

Tocotrienols In 1964, a few decades after the discovery of tocophenols, tocotrienols were discovered (12). Since this discovery, an abundance of research continued with tocopherols and tocotrienols. Although tocopherols are the most common form of vitamin E, tocotrienols possess many beneficial properties as well. Only a small percentage of studies have focused on tocotrienols and most of the studies involve plant and animal research rather than human research. Before promoting health benefits and recommendations to the population, more extensive research needs to be conducted. The discoveries for tocotrienols, although continually changing and updating, have found to have many beneficial properties to human health. Some of these properties are proven to have more powerful antioxidant and anticancer effects on the human body than tocopherols. It has also been established that tocotrienols have lipid-lowering, neuroprotective, antidiabetic, antiatherogenic, and anti-inflammatory effects and also have the ability to lower blood pressure (7). The reason that tocopherols are more recognized is due to the fact that this form of vitamin E is more abundant in nature. Tocotrienols exist in a lower level concentration in food than tocopherols. This is rather unfortunate, given their multiple discovered benefits in recent years. Efforts to extract this particular form of vitamin E for use in disease prevention and health are becoming more prominent (12).

Vitamin E Structures The structures of tocopherols and tocotrienols are very similar. They contain the same basic chemical structure with a single, extending side chain. The main difference between the two lies in the double bonds and the chiral centers of each structure. The side chain on tocotrienols contains three double bonds, whereas the side chain on tocopherols do not contain any (Figure 1). These double bonds on the unsaturated chain of tocotrienols provide more effective metabolic functions than tocopherols. They also allow for better permeation into the fatty tissue layers of the body than tocopherols (7). The chiral centers of each of these structures differ in that tocotrienols contain one chiral center and tocopherols contain a total of three chiral centers (Figure 1). The chiral centers on chemical structures are indications of how many stereoisomers are possible for that specific molecule (8).

Figure 1. (7)
(* Indicate chiral centers)

Metabolic Pathway When vitamin E is ingested, it goes through a series of processes for it to be effectively absorbed and beneficial in the human body. Digestion begins in the mouth where the enzyme, lingual lipase, is released to activate the breakdown process. The nutrient then makes its way to the stomach where it is emulsified by the churning process. The enzyme, gastric lipase is released in the stomach in order to break down the molecule. Vitamin E continues through the body and enters the main site for lipid digestion, the small intestine. This entry into the intestine sends a signal for cholecystokinin (CKK) to be released, which then signals the release of bile and pancreatic lipase from the gallbladder and the pancreas. Once broken down, the vitamin and other nutrients like triacylglycerol, phospholipids, cholesterol, and proteins, are combined together in what are called chylomicrons. These chylomicrons transport the newly formed lipids into the lacteal and then to the thoracic duct (11). At this point, the vitamin enters the blood and can be readily used throughout the body. Cytochrome P450 metabolizes vitamin E and then it is excreted in the urine (4). All forms of vitamin E go through this similar process, however, alphatocopherol is the only form that appears in the blood plasma. The other forms are excreted.

Availability Vitamin E can be consumed naturally from many different sources or it can be consumed in a synthetic form, as a food supplement. It is also common for certain foods, or even products like

oils and lotions, to be fortified with vitamin E to increase their nutritive content. The natural form of vitamin E exists in the eight different isomers discussed previously. Each of these forms have different levels of biological activity however, alpha-tocopherol is the only form that is successfully absorbed in the blood and is able to meet the needs for human dietary requirements. This is the reason alpha-tocopherol is used as the standard form of vitamin E in the human diet.

When comparing the natural sources of nutrients to the supplement forms, most synthetic sources of vitamins can be used in place of the natural ones without loss a of efficiency. However, vitamin E is much different and it is most commonly recommended that a natural intake of this vitamin is the best choice. Although natural and synthetic forms of vitamin E contain the same molecular formula, they are arranged slightly different, making synthetic vitamin E not as efficient in absorption. After the body absorbs synthetic vitamin E, the protein in the liver will only recognize the naturally occurring form and excrete the rest. Of the eight isomers contained in synthetic vitamin E, only 12.5% is the naturally occurring form that will be absorbed, hence why natural over synthetic is preferred (13).

Natural Form The main, natural source for vitamin E is found in vegetable oils, nut oil, olive, nuts, seeds, egg yolk, cheese, margarine, oatmeal, soya beans, avocados, and leafy green vegetables (8). Significant levels of tocopherols are found in a variety of nuts and nut products. The consumption of this plant protein not only provides a good source of Vitamin E, but is also high in fiber, arginine, copper, and magnesium (6). Tocopherols and tocotrienols are found separately in certain foods more than others. The vitamin E component, tocopherol, is found primarily in olive, sunflower, corn, and soya bean oils. Tocotrienols can be found mainly in palm oil, barley and rice bran (8). Increasing these types of foods in ones diet can be very useful in improving health.

Synthetic Form Although vitamin E is found naturally in many sources, it can also be consumed in a synthetic form through supplements. In food supplements, tocopherols and tocotrienols are usually combined into softgel capsules (7). Synthetic vitamin E is comprised of both tocopherols and

tocotrienols. It contains all eight possible stereoisomers, only one of which is the naturally occurring vitamin E, RRR-alpha-tocopherol, making the synthetic form less effective in obtaining adequate nutrients. About twice as much of the RRR-alpha-tocopherol synthesized by plants is absorbed in the body as compared to synthetic RRR-alpha-tocopherol. Supplement use however, can be particularly beneficial for individuals with specific health problems or deficiencies relating to vitamin E. It is recommended that a higher amount of synthetic vitamin E be consumed as compared to natural in order to acquire the same nutrient content.

Recommended Dietary Allowance The Recommended Dietary Allowance (RDA) refers to the average daily intake level that is sufficient to meet the nutrient requirements of almost all (97%98%) healthy people (14). Vitamin E is a fat-soluble vitamin, meaning that it does not need to be consumed every day in order to meet the recommendations. When this vitamin is consumed, the body uses what it needs at that time and the remaining nutrients are then stored in the fat tissues of the body use at a later time. The RDA for vitamin E increases gradually with age. There is inadequate data to support the level of vitamin E needed for infants so instead of basing their needs on the RDA standards, Adequate Intake (AI) levels were established. Between 0-12 months of age, AI levels are used in place of RDA levels. The amount of required vitamin E slowly increases between the ages of 114 years, beginning at 6 mg per day to 15 mg per day, where it remains constant (Figure 2).

Figure 2. (14) Toxicity

At this point in time, there is no evidence that shows a dangerous level of vitamin E intake from natural food sources. However, there are possible side effects regarding increased levels of vitamin E from supplements (14). Vitamin E toxicity and an increased risk of hemorrhagic stroke have been linked in many studies. One study in particular showed that, with an increase in vitamin E supplement intake, there was a 22% increase in hemorrhagic stroke risk (9). The Food and Nutrition Board (FNB) at the Institute of Medicine of The National Academies established Tolerable Upper Intake Levels (ULs) to eliminate the potential risks from this toxicity (Figure 3).

Figure 3. (14)

Deficiency Vitamin E deficiency is defined as less than 500 mg/dL. Although a deficiency in this particular vitamin is rare, it may appear in people who have mild anemia, ataxia, or color changes in the retina. It is also possible to see this type of deficiency in premature infants or people who are not able to absorb fat as readily (8). Premature infants are at risk, not only vitamin E, but vitamin A deficiency as well because they do not have adequate storage or intake of these vitamins. It is also due to their inability to absorb the vitamins and their increased needs, as compared to regular term infants (2). The side effects of a deficit in vitamin E can result in problems like neurological degeneration, muscle weakness, retinal degeneration, poor transmission of nerve impulses, or impairment of the immune response (3). It is more common for people with disordered fat absorption to come across this type of deficiency because the digestion process requires fat for the absorption of vitamin E. The effects that come along with a vitamin E deficiency can be detrimental to human health. Supplement intake is one approach that individuals with this deficiency can take to correct health problems. Although dietary intake of

this vitamin is the most preferred and effective source, it may be difficult to obtain all of these nutrients from food. Supplements can increase the amount of vitamin intake and correct the deficiency at an earlier state before it may become severe.

Benefits Vitamin E is considered to be an exceptionally beneficial nutrient in the human diet. There are many factors that isolate this vitamin from others, based on the way they affect the body. These vitamins, along with many other vitamins and minerals, are known to have powerful antioxidant capabilities. Antioxidants in the human diet have been researched for many years and are proven to reduce the damaging effects of oxidative stress. Free radicals are produced as a result of oxidative stress and, as they interact with cells in the body, damage to the body transpires. This can result in the promotion of numerous diseases such as atherosclerosis, cancer, heart disease, hypertension, Alzheimer disease, Parkinsons disease, hypertension, diabetes, and aging (10). Oxidative damage occurs naturally but factors such as physical activity level, stress level, pollution, smoking, or diet can increase the rate of this process. Improving your diet by incorporating antioxidant rich foods can counteract the damaging effects of free radicals that are produced from oxidative stress. Foods like tea, coffee, dry beans, bananas, apples, tomatoes, and potatoes are a few that contain high levels of antioxidants (10). The two main vitamins that contain antioxidant properties are vitamin C and vitamin E. Vitamin E prevents and treats many nutrient related diseases, and it can be especially significant for disorders relating to heart disease, cancer, and cognitive functions.

Cardiovascular Disease There are many diseases can be defined as a cardiovascular disease. This is because cardiovascular disease refers a disease of the heart and blood vessels, otherwise known as heart disease. Many of these diseases are linked to poor dietary intake. Studies have shown that an increased vitamin E intake prevents the oxidation of low-density lipoprotein cholesterol (LDL) (14). This type of cholesterol is a major contributor to the onset of plaque buildup in the arteries, also known as atherosclerosis. It has also been studied that by combining a low dose of tocotrienol mixture and other factors like therapy and the drug, Lovastatin, can also lower a persons risk for heart disease by reducing the cholesterol agent (8). Another way that vitamin E

has been proven to help with cardiovascular disease is by inhibiting the formation of blood clots. When blood clots are formed in the body, venous thromboembolism or a heart attack could result. Statistics show that heart disease rate was 30% to 40% lower in those with increased vitamin E supplement intake (14). There have been multiple studies that show little effect of vitamin E on preventing or treating heart disease and there are many that show that there is a positive correlation between the two. Like many other vitamins and minerals in the diet, research is continuously being conducted to discover the true potential of this nutrient.

Cancer Cancer has become much more prevalent in recent years. There are many forms of cancer known to society, all of which can be detrimental to human health and function. Although further studies need to be conducted to determine the true potential of vitamin Es role in the prevention or treatment of this disease, there is relevant research that proves its benefits. In cancer, a process called lipid peroxidation occurs and produces a number of genotoxic free radicals. Vitamin E is known to prevent lipid peroxidation which could ultimately protect DNA from cancerous damages (1). A few cancerous diseases that vitamin E has been associated with improving or preventing are colon cancer, breast cancer, and bladder cancer.

Cognitive Functions Vitamins are a major factor in brain function and development. Vitamin E exists in all cell membranes and is essential in sustaining optimal neurological function (3). Over time, free radical damage affects the cells in the brain resulting in cognitive decline. Diseases like Alzheimers disease or Parkinsons disease are a few that are a result of this oxidative damage (14). As an antioxidant, vitamin E has the potential to counteract these nerve damaging actions and provide some protection. Supplementation or dietary vitamin E can help with cognitive function because of its beneficial antioxidant properties.

Conclusion

Fat-soluble vitamins are essential in maintaining health and they provide a variety of nutritional benefits to the human body. The actions of antioxidants are particularly important in lessening

the damaging effects of oxidative stress on the body. It is important that the recommended levels of vitamin E are consumed in order to prevent nutrient related diseases and to decrease oxidative stress. The benefits of consuming vitamin E almost always relate to its role as an antioxidant. Consumption of this vitamin through natural, dietary sources is the best option for individuals to obtain an optimal health status. Vitamin E is especially known for being a highly nutritive, fat soluble, antioxidant and can improve and maintain health in ways more than one.

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