VITAMIN E
SUPPLEMENTATION
I. NUTRITIONAL ASPECTS OF VITAMIN E
II. VITAMIN E AND MUSCLE DAMAGE
III. INCREASED OXYGEN UTILIZATION
VI. EFFECT OF DIET ON LIPID PEROXIDATION
VII. VITAMIN E SUPPLEMENTATION AND LIPID PEROXIDATION
I. NUTRITIONAL ASPECTS OF VITAMIN E
Antioxidants can be delivered to a person’s system in three ways, eating food in which they naturally occur, eating foods that have been fortified with vitamins, or taking a vitamin supplement. As long as they are consuming a well-balanced diet, including a variety of foods and lots of fruits and vegetables, most athletes consume adequate amounts of beta carotene and vitamin C.(4)
Vitamin E is another story. Getting enough vitamin E in your diet may be tricky. Vegetable oils are the primary source of vitamin E in Western-type diets. Fruits and vegetables combined have been reported to provide more than 20% of the vitamin E in the US diet, and additional food sources are breakfast cereals, eggs, wheat germ, seeds and nuts(27). Since it is fat-soluble and unfortunately found in limited amounts in only a few foods it’s likely that the average athlete will not meet his or her RDA of 10mg for vitamin E.(4,15) There is a very strong link between vitamin E and the prevention of tissue damage, but to get the beneficial amount of vitamin E you would have to ingest large amounts of vegetable oil. Since there are 90 calories of pure fat in only a tablespoon of oil, there are few athletes who would be willing to consume a whole cup. That is when a vitamin E supplement and supplements are really beneficial.
Because vitamin E is mostly found in high-fat foods, most athletes can not get enough even if they eat
well. Since they generally eat lots of carbohydrates while cutting fat, it is impossible for them to get
enough vitamin E. With the trend in this country toward low-fat diets, especially among female
athletes, we have seen a dramatic decrease in dietary fat, and when that is reduced, so typically is
vitamin E. There are many ways to decrease fat from the diet, and in the broad scope of things that
seems really good. When you look at it a little more microscopically, you can see that vitamin E gets
a little shorted. This puts athletes at risk of cell damage.(4,15)
II. VITAMIN E AND MUSCLE DAMAGE
Strenuous or unaccustomed physical exertion often results in damage to the exercising muscle groups, with subsequent loss of muscle function, release of muscular enzymes, histological evidence of damage and muscle aching.(6)
The form of the contractile activity that the muscle undertakes appears to greatly influence the amount of damage that is produced. In concentric activity, a muscle is allowed to shorten during activation; in isometric activity, a muscle is activated but not allowed to shorten; and in eccentric activity, the muscle is lengthened during activation. Muscles are injured to a greater extent when exercise involves predominantly lengthening contractions than when an isometric or shortening contraction is involved.(6)
In eccentric exercise a lower number of motor units are recruited compared with the same exercise conducted concentrically. This implies that, in eccentric exercise, the mechanical stress per fiber is higher than in concentric exercise.(6)
Exercise of a sufficient intensity and duration has been shown to increase indicators of oxidative stress.(9) Oxidative stress is the term used to describe the condition of oxidative damage resulting when the critical balance between free radical generation and antioxidant defenses is unfavorable.(27,28) Oxidative stress caused by excessive exercise has been indicated in skeletal muscle, as indicated by the by-products of lipid peroxidation.(9,27,32) Various forms of physical exercise are followed by elevations of tissue enzymes serum creatine kinase and lactate dehydrogenase levels. For the most part, increased levels of tissue enzymes in serum have been used as indirect indicators of cell permeability resulting from tissue membrane damage. It has been postulated that the damage might be related to free radical-mediated lipid peroxidation.(6)
Thus during excessive exercise, in addition to mechanical forces, the production of free radicals and
the initiation of peroxidation reactions may contribute to tissue damage.(4,6,15)
III. INCREASED OXYGEN UTILIZATION
The driving force for muscular exercise is the conversion of chemical bond energy to mechanical energy. Energy for muscle contraction is delivered from ATP. However, as the intracellular stores of ATP are limited, ATP must continuously be regenerated through various metabolic pathways. The most efficient path for ATP regeneration is through oxidation of the local stores of glycogen and fat in the musculature. The final part of this oxidation process requires molecular oxygen as an electron acceptor and proceeds in the Kreb’s cycle and electron transport chain of the mitochondria.(31) Exercise increases oxygen utilization and the flow of electrons through the electron transport system where most of the oxygen is utilized by the mitochondria for energy production by oxidative phosphorylation. However, ~2-4% of the oxygen from the respiratory chain can form superoxides as electrons escape from the ubiquinone step of the system.(10)
Free radical production and subsequent lipid peroxidation, i.e. peroxidation of membrane
polyunsaturated fatty acids, are normal sequelae to the rise in oxygen consumption concomitant with
exercise, and are positively correlated with increases in skeletal muscle damage.(6,14) It is very likely,
considering this rise, that free radicals are produced to a greater extent during exercise than during
rest.(6) All cells exposed to molecular oxygen are at risk of being damaged by O2-derived free
radicals (e.g., superoxide anion radical, hydroxyl radical) and lipid peroxidation products.(2)
Free radicals are unstable singlet oxygen molecules or fragments of molecules with unpaired electrons in their outer orbitals. They strive to balance their unpaired electrons by combining with electrons with opposite spins in other substances. Therefore, they are highly reactive. Oxygen free radicals include the superoxide radical, hydrogen peroxide and the hydroxyl radical. In an attempt to balance their unpaired electrons, the free radicals go to oxygen-rich cell membranes.(4,6,19) Hydroxyl radicals rapidly react with polyunsaturated fatty acids in the cell membranes. The reaction of hydroxyl radicals with lipids in the cell membrane is called lipid peroxidation. The lipid membrane layer is in the form of a fluid-mosaic bilayer with receptor and transport proteins intertwined. The fluid property of the membrane is due to the many polyunsaturated fatty acids, and the viability of the cell is dependent on this membrane property for protein flexibility.(10,31) Lipid peroxidation of cell membranes causes a loss in fluidity as well as an increase in the permeability of membranes with loss of cytosolic proteins as a result. One of the more harmful effects of a free radical attack on a lipid is that the lipid itself becomes a reactive peroxyradical, thus initiating a free radical chain reaction. Peroxyradicals appear to be able to travel in the bloodstream and initiate peroxidation at locations from their origin.(31) Lipid peroxidation initiated by free radical reactions is associated with tissue necrosis.(19) Peroxidation of membrane lipids can also lead to a number of other changes in cell functions, such as increased membrane permeability, decreased Ca++ transport in the sarcoplasmic reticulum (SR), altered mitochondrial function, formation of toxic metabolites and alteration of the metabolism of intracellular glutathione (an antioxidant).(6)
Attack of free radicals on the polyunsaturated fatty acids of cell membranes causes the formation of hydroperoxides with conjugated dienes. These hydroperoxides can undergo decomposition to numerous aldehyde products of different chain lengths. The 3-carbon chain malondialdehyde (MDA) is one of the major aldehydes formed. MDA is a frequently used indicator of lipid peroxidation in biological tissues.(31)
Under normal circumstances, free radicals that are produced through biological processes and in
response to exogenous stimuli are controlled by various enzymes and antioxidants in the body.
Laboratory evidence suggests that oxidative stress occurs when free radical formation exceeds the
ability to protect against them, and may form the biological basis of exercise-induced tissue
damage.(27) This has been documented by numerous investigations demonstrating increases in the
by-products of lipid peroxidation following exercise.(9) During exercise, it is clear that these enzymes
are not always adequate in preventing exercise-induced lipid peroxidation.
Humans are endowed with an elaborate antioxidant defense system to protect the cells against oxygen-centered free radicals. Exercise, however, seems to perturb the fine balance of the defense system. The efficiency of the antioxidant defense system depends on adequate dietary vitamin and micronutrient intake and on endogenous production of antioxidants. Antioxidants are substances that help to reduce the severity of the oxygen stress either by forming a less active radical or by reducing the activity of radical induced reactions.(6,9,15) If the rise in oxygen free radical level exceeds the antioxidant defense capacity of the cells lipid peroxidation will occur.(6) Vitamin E, also known as a-tocopherol, is the most important lipid-soluble antioxidant in humans; it works to quench free radicals and acts as a terminator of lipid peroxidation within cellular membranes.(2,14) The major pool of vitamin E is located in the mitochondrial membranes. Vitamin E is highly lipiphilic and acts as a chain-breaking antioxidant by forming more stable tocopheroxyl radicals.(31,34)
Because a-tocopherol is fat soluble, absorption and utilization depend substantially on the presence of dietary lipids, pancreatic secretions, and bile in the gastrointestinal tract.(9,28) The amount of lipid available influences lipid peroxidation.(10) Approximately 70% of the amounts of a-tocopherol taken orally are absorbed with large amounts found in the liver, adipose tissue, heart, adrenal cortex, and muscle.(9) Vitamin E appears to be located within membranes with the phytyl tail closely aligned with acyl chains of lipids in the membrane. The chromanol head of vitamin E appears to be close to the surface of the membrane. It is thought that when a peroxyl radical is formed in the tail region it is forced or projected out of the nonpolar region toward the polar region where the chromanol head is located. This would enable the chromanol region to be oxidized and possibly enable vitamin C in the aqueous region to interact and regenerate the chromanol region of vitamin E.(9,28)
The distribution of a-tocopherol does not appear to be homogeneously distributed in the membrane. The majority of a-tocopherol was associated with the most fluid zones of the membrane probably near the unsaturated fatty acids. (9)
Polyunsaturated fatty acids, which are present in large quantity in the membrane, are very susceptible to radical attack and are carried by low-density lipoproteins. Low-density lipoprotein carries within it a number of antioxidants that can trap free radicals and prevent the chain reaction from starting or limit its extent. When low-density lipoprotein is subject to pro-oxidant conditions, these endogenous antioxidants are first oxidized themselves before the actual oxidation of the polyunsaturated fatty acids can occur. The period preceding the oxidation, in which tocopherol is consumed, is called the lag phase. After depletion of low-density lipoprotein of all antioxidants, lipid peroxidation rapidly accelerates and all the polyunsaturated fatty acids are quickly oxidized. The duration of the lag-phase is determined by its antioxidant content.(6)
Thus, increasing the antioxidant content of the low-density lipoprotein (with tocopherol, for example), will result in more protection of the membranes to lipid peroxidation.(6) If the concentration of vitamin E is inadequate in the membranes, it has been shown that this may lead to lipid peroxidation. Studies using vitamin E-deficient animals have clearly demonstrated an increased susceptibility to lipid peroxidation. Vitamin E deficiency can result in loss of membrane integrity, reduced oxidative capacity, and increases in lipid peroxidation. Subclinical levels of vitamin E in the diet of animals was shown to potentiate skeletal muscle damage. Animals maintained on a low or deficient vitamin E diets have reduced tissue levels of vitamin E. Mice with vitamin E deficient diets showed a loss of a-tocopherol in skeletal muscle and heart as well as increased lipid peroxidation. In studies performed by Goldfarb et al. (9,10) vitamin E reduced the amount of hydroperoxides and TBARS (marker of lipid peroxidation) in plasma. This suggests that the vitamin E was able to protect muscles from exercise-induced oxidative stress.
Estrogens are female sex hormones that may also protect against peroxidative damage of membrane lipids and low density lipoproteins (LDL). Studies have reported that female rats have greater protection against free radical induced lipid peroxidation and muscle damage consequent to exercise than do male rats. It has been suggested that the lower susceptibility to exercise-induced oxidative stress and muscle membrane disruption of female rats may be due primarily to the antioxidant and membrane stabilizing properties of estrogens. Studies on humans have indicated that the lower incidence of atherosclerosis seen in premenopausal females in comparison to males is due in part to the ability of estrogens to diminish LDL peroxidation.(34)
In contrast to all other natural steroids, estrogens have a hydroxyl group on their "A" ring in the same
location to that found on vitamin E. By donating a hydrogen atom from their phenolic hydroxyl group
to peroxyradicals, estrogens may be able to terminate peroxidation chain reactions and thus act as
antioxidants in a manner similar to vitamin E. According to Tiidus (34), estrogens are a major factor
affecting muscle membrane stability and CK release.
VI. EFFECT OF DIET ON LIPID PEROXIDATION
Food intake exerts a complex influence on the bioavailability of micronutrients and drugs. In a study conducted by Dimitrov et al. (7), plasma elevation of a-tocopherol was affected by dietary fat intake. Individuals consuming a high-fat diet showed significantly greater plasma a-tocopherol concentrations as compared with those fed a low-fat diet. Administration of 880 mg of vitamin E for 5 days and the high-fat diet resulted in higher average plasma concentrations of a-tocopherol than does the same dose of vitamin E taken with a low-fat diet. Even with a low-fat diet, ingestion of a-tocopherol produced an increase in plasma concentrations. A study produced by Lehmann et al. (17) showed that when the percentage of fat intake increased in the diet, the average content of a-tocopherol increased. The authors also stated that when blood lipids drop, the reduction in carrier lipoproteins may cause a concomitant decrease in blood tocopherols.
Vitamin E nutritional status customarily has been estimated by measuring plasma tocopherol
concentrations. In addition, high correlations between plasma tocopherol and plasma lipid
concentrations were reported by several investigators.(6) Horwitt et al.(7) suggested that because
plasma tocopherol concentrations tend to rise and fall with blood lipids, both values should be
reported and that the ratio of the two might more accurately reflect vitamin E status.
VII. VITAMIN E SUPPLEMENTATION AND LIPID PEROXIDATION
Antioxidant vitamin intake has a favorable effect on the process of lipid peroxidation. The question of whether antioxidant vitamins and antioxidant enzymes protect against exercise-induced muscle damage can be answered affirmatively. Increased antioxidant activities and antioxidant level are able to counteract the lipid peroxidation process by scavenging free radicals and protecting the muscle from being damaged during exercise.(6) Previous studies have reported that MDA, an indicator of lipid peroxidation, increased in muscle and blood immediately after exercise to exhaustion. Sumida et al. (32) found that MDA did not increase immediately after the vitamin E supplementation exercise despite the fact that the same maximal exercise intensity was achieved in the vitamin E and control exercise, rather it was decreased significantly. A study completed by Kanter et al. (14) also showed that taking a-tocopherol served to lower markers of lipid peroxidation at rest and after exercise. In the same study the authors stated antioxidant vitamin supplement brought about significant reductions in MDA concentration. Turley and Brewster (37) also report that a-tocopherol decreases membrane lipid peroxidation.
Various studies have indicated that deficiencies of individual antioxidant vitamins can potentiate oxidant stress and that supplementation with individual vitamins, particularly vitamin E, may attenuate lipid peroxidation.(10,14,32,37) Supplementation with antioxidant vitamins can decrease the absolute levels of lipid peroxide markers produced during exercise.(14) Wander et al. (38) showed that with supplementation of a-tocopherol, plasma a-tocopherol concentration increased up to 70% compared with its value without any supplementation. According to Goldfarb et al. (10), vitamin E supplementation can help to reduce oxidative stress induced by exercise. The authors concluded that supplementation of vitamin E was apparently successful in preventing the increase in lipid peroxidation. In a study performed by Rokitzki et al. (29), a-tocopherol serum concentration increased significantly in the a-tocopherol supplemented group. Also, the increase of creatine kinase (CK) serum concentration, an indicator of the extent of muscle damage, was remarkably lower in the supplemented group compared with the placebo group. It is concluded that endurance training coupled with antioxidant vitamin supplementation reduces blood CK increase under exercise stress.(10)
According to Goldfarb et al. (10), vitamin E deficiency has been seen to reduce endurance performance. Because vitamin E levels have shown decreases in muscle with endurance training, endurance exercise may require a greater need for vitamin E.(9) A consideration of the human studies reviewed shows that antioxidant vitamin supplementation can be recommended to individuals performing regular heavy exercise. Trained individuals have an advantage over the untrained, because training results in increased activity of several major antioxidant enzymes, and a better overall antioxidant status.(6)
It must be kept in mind that the availability of oxygen is a prerequisite for the survival of higher organisms and that free radicals are continuously produced in the human body. Some of these oxygen species have beneficial effects, but when they are produced in excess, beyond the antioxidant capacity of the body, the toxicity of oxygen becomes evident and they can cause tissue damage.(6) Therefore, vitamin E supplementation may be beneficial, due to its characteristic protection of the living cell from damaging oxidative effects, which are produced during endurance exercise.
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