An Inverse Relationship Between Cardiovascular Disease and Vitamin C and Vitamin E - Research Paper Example

 ABSTRACT: Cancer, the second most common cause of fatality in the United States of America (USA), reportedly affects all age group and involves various organs in the human body. Several factors are known to cause disease state in our body, and one of these factors causing cancer is the oxidative stress. A complex mixture of oxidants and antioxidants originates from the human diet, and the major site of this antioxidant action comes from the gastrointestinal tract. To understand better the relationship linking cancer and antioxidants, it is essential therefore to know them separately. Numerous degenerative diseases are associated with long – term accumulation of damaged free radicals, and these antioxidants work simultaneously to maintain strength and well – being by protecting our body from the harm brought about by these free radicals that injure cells and tissues that are healthy. Dietary foods rich in fruits and vegetables are known to protect against various illnesses such as cardiovascular diseases and epithelial cancers. Continuous production of free radicals is generated during oxidative metabolism, and its damage is limited by the action of antioxidants that scavenges the action of these free radicals. Among the naturally occurring antioxidants are vitamin C, selenium, vitamin E, beta – carotene, and lycopene. I. OBJECTIVE OF THE STUDY: (1) To know the mechanism that leads to the production of oxidants in our body; (2) To investigate the role of antioxidants in the prevention of cancer progression; (3) To know the different types of antioxidants; and (4) To know the relationship between the different anti – oxidants and its effect on cancer and diseases. II. INTRODUCTION: Cancer, the second most common cause of death in the United States of America (USA), affects all age group and involves various organs in the human body (Murray, et al., 1996). Diminished or unrestrained growth control, local tissue invasion, and metastasis are the three characteristic properties of cancer cells (Murray, et al., 1996). Murray, et al. (1996) added that radiant energy, chemical compounds, and viruses are the agents known to cause cancer. Bjelakovic, Nikolova, Simonetti, and Gluud (2004) stated that other factor that causes cancer is oxidative stress. Murray, et al. (1996) and Wiseman and Halliwell (1996) noted that an evidence of free radical involvement and other reactive molecules in the causation of disease course is growing. Bielakovic, et al added that a complex mixture of oxidants and antioxidants comes from the human diet, and the major site of this antioxidant action is from the gastrointestinal tract. Gene mutation and carcinogenesis are promoted by oxidative injury, and subsequently, cell death or apoptosis ensues in the human cells. Bielakovic, et al. noted that gastrointestinal diseases including cancer can be caused by apoptotic dysregulation since oxidative stress modulate the programmed apoptosis. A statistical correlation between disease incidence and low antioxidant levels of blood or diet antioxidant nutrient in the epidemiological studies was reported (Murray, et al., 1996). For this reason, much attention has led the public to investigate whether supplementation with antioxidants protects an individual against cancer (Bielakovic, et al., 2004). And to understand the relationship between cancer and antioxidants, it is essential to know them as a separate entity. A. What is Antioxidant? Packer (undated) defined antioxidants as a group of naturally occurring compounds formed by body, which are acquired from many foods. During the late decades of our life, these antioxidants work simultaneously in our body to maintain strength and well – being by means of protecting our body from the damage brought about by these free radicals in the human cells and tissues (Packer, undated). Packer added that in every disease such as cancer, heart disease, arthritis, and cataracts, these free radicals are believed to be the causal factor. Antioxidants make a difference in life and death and aging process by controlling the production of free radicals in our body (Packer, undated). The role of these antioxidants in our body is considered by Packer as “nothing less than miraculous” and the profound function of these antioxidants is more appreciated in keeping our body healthy. Packer noted that an intense role in keeping our body in good physical shape is well appreciated when the role of antioxidants are well understood and appreciated. Antioxidant micronutrients such as vitamin A, carotenoids, vitamin C, and vitamin E were proven during in vitro studies to have cancer chemopreventive properties, namely, antioxidant effects, cellular signaling regulation, differentiation of cells, proliferation of cells, and apoptosis (Huang, et al, 2003). A relationship between the disease state and antioxidant has been well - studied and became highly profitable. As a result, it has expanded our understanding on various disease etiologies and ways a malady can be prevented (Temple, 2000). B. What is Free Radical? Murray, et al. (1996) defined free radical as “an atom or molecule that has one or more unpaired electrons.” Free radical is made highly reactive because of its tendency to gain an electron from other substances. It is widely believed that reactive species of oxygen are involved in the aetiology of various diseases, and this has been indicated by the signs of oxidative stress (Temple, 2000). Temple (2000) added that in mid – 1960’s, Professor Sanojki, a Russian toxicologist, in a World Health Organisation (WHO) meeting, linked reactive oxygen species (ROS) as the aetiology of different degenerative or “rusting diseases.” ROS, which include singlet oxygen, the superoxide anion radical, peroxide anion, and hydroxyl radical, are free radicals that are highly reactive produced from molecular oxygen (Temple, 2000). During normal cellular respiration, as part of normal response of immune system of activated leucocytes and by exogenous oxidants, these ROS is generated and is capable of harming vital cellular components that includes lipids, proteins, and DNA (Temple, 2000). C. How do Free Radicals leads to Cancer? Weisburger (1999) stated that a complex series of stepwise process is involved in the causation and development of cancer. In a normal steady state, the body continuously generate and extinguish free radicals; however, it is coupled that numerous degenerative diseases are associated with long – term accumulation of damage of free radicals (Temple, 2000). Oxidative stress has been heavily implicated in disease spectrum and dysfunction states of the body, and Temple enumerated conditions that are known to be associated with oxidative stress. These are: (1) immune system impairment, (2) insulin and non insulin dependent diabetes mellitus, (3) cancer, (4) immune conditions that includes rheumatoid and ankylosing spondylitis, (5) different respiratory related diseases, (6) diseases of the eye that includes cataracts and retinal damage, (7) Alzheimer’s disease, and (8) schizophrenia. Bjelakovic, et al. (2004) concurred in his document with Temple’s statement noting that cancer is caused by oxidative stress. Bjelakovic, et al added that a complex mixture of oxidants and antioxidants occurs in the human body. Murray, et al. (1996) explained that four electrons are acquired when cytochrome oxidase reduces oxygen to water. Univalent reduction, which accounts for 1 – 5% of total consumption of oxygen, gains electron one at a time. Highly reactive individual molecules such as superoxide free radical, hydrogen peroxide, and hydroxyl free radicals, which resulted from the univalent reduction, are potentially destructive to the tissues (Murray, et al., 1996). Murray, et al. added that superoxide can also be produced from neutrophil stimulation (one mechanism for bacterial destruction). Xenobiotic metabolism by cytochrome P450 also produces superoxide, This is because of the fact that this reactive molecules act in the site very close to where they are generated making most of the cell structures such as membranes, structural proteins, enzymes, and nucleic acid vulnerable to mutation and cell death (Murray, et al., 1996). D. The Correlation between Free Radical and Antioxidant. (How might antioxidant prevents cancer) Murray, et al. (1996) stated that a growing evidence of free radical and other reactive molecule involvement in the disease process has been noted. This has been evident from epidemiological studies that show a statistical correlation between disease incidence and low level of blood or dietary antioxidant nutrients (Murray, et al., 1996). This is observed with respect to cancer and selenium, vitamin A, β – carotene, vitamin C, and vitamin E (Murray, et al., 1996). An inverse relationship between cardiovascular disease and vitamin C and vitamin E incidence has been correlated, and this has been related with others studies that showed macrophages and foam cells taking up oxidised LDL. Consequently, a beneficial effect on the aforementioned process has been observed in probucol, a certain type of antioxidant drug (Murray, et al., 1996). Increasing evidence also noted that skin damaging effect of ultraviolet rays can be protected by topical vitamin E drug (Murray, et al., 1996). Packer (undated) noted that free radicals, the naturally occurring by-product of normal processes of the cells, is neutralised by the antioxidants, and these free radicals are formed from exposure to various factors in the environment such as tobacco smoke and radiation. In addition, Packer revealed that the most common free radical in human is in the form of oxygen. Oxygen brings about damage to the DNA and molecules of the cells when they try to steal electrons from other molecules causing damage to different molecules and DNA. Packer highlighted that cancer is eventually formed over time period when the damage brought about by these free radicals in the cells becomes irreversible. Eastwood (1999) noted that dietary foods rich in fruits and vegetables are known to protect against various diseases such as cardiovascular diseases and epithelial cancers. As mentioned, continuous production of free radicals is produced during oxidative metabolism, and its damage is limited by the action of antioxidants that scavenges the action of free radicals (Eastwood, 1999). Chain breaking antioxidants are exhibited by compounds with low molecular mass having range of solubility properties, and among these compounds acting as scavengers are ascorbate, glutathione, and urates (Eastwood, 1999). Other scavengers include carotenoids and sterically hindered phenols (e.g. α – tocopherol and flavonoids). Eastwood added that hydroxycinnamic acids, p – coumaric acid and ferulic acid provides a link between the dietary fiber and antioxidants. This is best illustrated by the cross – linkage dimers formed by C6 – C3 phenols with fruits and vegetables’ plant cell – wall structural polysaccharides. On the other hand, in the vacuoles of plant cells, feruloyl β – glucoside, an example of hydroxycinnamic acids, are found as its soluble conjugates (Eastwood, 1999). These hydroxycinnamic acids contained within vacuoles will be absorbed from the small intestines when these fruits and vegetables are eaten, and in the colon, these hydroxycinnamic acids will be released and absorbed (Eastwood, 1999). Eastwood stated that among the antioxidants dispersed in a non – uniform manner between various phases in the cells and compartments of the body, synergism transpires. An indirect role of water – soluble antioxidants exist in protecting the membrane and lipoprotein. Eastwood then concluded that the aforementioned mechanism is achieved in a chain reaction through antioxidant activity of polyphenols, tannins and hydroxycinnamic acids, intermediary partition coefficient, and lipoic acid. E. Where can we find antioxidants? Temple, et al., (2000) referred nutrient as substances which are essential and a good example for this are vitamins; while, nonessential nutrients such as phytochemicals are substances that are plant based having an effect that is beneficial in the body. Temple classified that antioxidants belong to both aforementioned class. Temple alleged that a close relationship linking oxidative stress and disease implies that antioxidants will be protective against disease state. This has been proven with the reduction of acquiring cancer and increasing fruits and vegetable intake (Temple, 2000). F. The amount of antioxidant occurs in food (nutrient and mineral). In Western countries, about thirty percent of cancers are thought to be secondary to dietary factors (Donaldson, 2004, Key, et al., 2004). Shacter and Weitzman (2002) thought that the best and safest means of cancer prevention is by eating diet rich in fruits and vegetables. A strong association of lower incidence of various forms of cancer are observed in epidemiologic studies among people eating diets with elevated amount of fruits and vegetables (Shacter and Weitzman, 2002). It is established in the epidemiological studies that lower risk of developing cancer are observed among people who consumes regularly fruits and vegetables than those who do not (Weisburger, 1991). Weisburger added that fruits and vegetables are excellent sources of vitamins, potassium, calcium, flavonoids, ellagic acids, indoles, and agents that play an important role in increasing enzymatic levels to detoxify carcinogens such as hydroxyl radicals and reactive oxygen. It has been postulated that antioxidant supplement consumption prevents some cancer types. The aforementioned belief is based on the fact that high levels of compounds of antioxidant are found in fruits and vegetables, and the capacity of oxidants to promote transformation to neoplasm (Shacter and Weitzman, 2002). G. Which kind of Antioxidant Affects Positively on Human in Cancer Diseases. Murray, et al. (1996) enumerated that the following are the reactive oxygen species (ROS) and their corresponding antioxidants. Oxidants (ROS) Antioxidants Singlet oxygen reactive species Vitamin A, β carotene, vitamin E Superoxide dismutase Vitamin E and β carotene Peroxyl free radicals Vitamin E and vitamin C Hydrogen peroxide Catalase and glutathione peroxidase Lipid peroxides Glutathione peroxidise Source: Murray, et al., (1996) Shacter and Weitzman (2002) stated that de novo carcinogenesis is inhibited by these antioxidants by enhancing antineoplastic therapy. During cancer treatment, these antioxidant compounds overcome the effects of chemotherapeutic agents that induce apoptosis. III. DISCUSSION A. Vitamin C Murray, et al, (1996) Weisburger (1991) noted that this active highly water – soluble essential nutrient, vitamin C, which is ascorbic acid itself, act as a powerful antioxidant. During digestion, they inhibit the formation of nitrosamines. A close relationship between the intake of vitamin C and reduction of risk in acquiring several types of cancer was noted in an epidemiological data (Temple, 2000). Weisburger (1991) stated that in various key oxidative and reductive enzyme systems, vitamin C is noted to participate indirectly. Temple (2000) reported that a close inverse relationship linking intake of β - carotene and cancer risk was long-established. Recently, a strong inverse relationship with several types of cancer, including cancers of the prostate, lung, and stomach with a carotenoid present in the tomoatoes lycopene, has attracted much attention in the research arena (Temple, 2000). Because of the endogenous carcinogen production of nitrites amongst the Orientals and Western Latin Americans, Weisburger (1991) considered that vitamin C accounts for the reduction of risk of cancer of the stomach. Additionally, Weisburger noted that in individuals who eat fruits and vegetables customarily, the risk of acquiring cancer of the oesophagus has been reduced significantly. Weisburger (1991) stated that due to increased turnover and metabolism during exposure to toxic pollutants, the requirement of vitamin C is increased. Hence, amount larger than the United States recommended RDA is required for vitamin C supplementation. B. Selenium Selenium, a potent protective nutrient, is a mineral with anticancer properties (Donaldson, 2004, Rayman, 2000 and 2005, and Letavayov´a, et al., 2006). Selenium is found in many active enzymatic sites that catalyze the reaction that encourages cancerous cells to undergo apoptosis, and improves the ability of the immune system to respond to various types of infection (Donaldson, 2004). Moreover, selenium also causes natural killer cell formation, induction of P450 enzyme found in the liver that eventually leads to detoxification of carcinogens, inhibits the prostaglandins, enhances fertility in the males, and decreases tumour growth rate (Donaldson, 2004). Temple (2000) and Rayman (2005) and Klein, et al., (2002) stated that evidence from experiments made in animals and international correspondence studies shows that selenium demonstrated antioxidant properties and is protective against cancer. Selenium is an integral component of glutathione peroxidase, and prior to damaging the membranes and other components of the cells, glutathione peroxidase provides a second line of defense against peroxidases (Murray, et al., 1996). Hence, selenium and tocopherol functions to support each other in their action against lipid peroxidases (Murray, et al., 1996). Together with vitamin E, other function of selenium includes normal function of the pancreas that is necessary for normal lipid digestion and absorption (Murray, et al., 1996). On the contrary, Murray, et al. noted that the requirement of selenium is reduced with vitamin E to prevent selenium to disappear from the body and maintain it in an active state. In food, other antioxidants with anticarcinogenic action are present in addition to vitamin C and carotenoids (Temple, 2000). Temple added that experiments made in animals established that selenium functions as antioxidant, and correlated other international studies and experiments made in animals that protective properties against cancer is exhibited by selenium. Temple reported that a strong inverse association between prostate cancer risk and selenium is exhibited in the data from the Health Professionals Follow – up Study, and these has been proven in a controlled intervention study reporting a 50% dramatic fall in total mortality secondary to cancer using selenium supplementation of 200 per day (Temple, 2000). Even though further studies are required on selenium, Temple noted that this type of antioxidant has proved its worth as a potent cancer – preventive agent. However, due to its risk of acquiring toxicity, it is essential that the dose of administration must not be excessive having its maximum dosage of 100 – 200 µg per day. C. Vitamin E (Alpha – tocopherol) Murray, et al. (1996) stated that the most potent antioxidant in the body acting as the first line of defense against polyunsaturated fatty acid peroxidation appears to be in the form of vitamin E. The recommended dietary allowance of vitamin E in the United States range from 5, 8, and 10 units in children, females, and males, respectively (Weisburger, 1999). In a variety of conditions, multiple protective effects are observed in vitamin E, and one of these effects includes nitrite destruction. Together with vitamin C, vitamin E is known for its excellent nitrite trapping effect (Weisburger, 1991). Murray, et al added that vitamin E is concentrated at mitochondrial phospholipids as well as at the endoplasmic reticulum and plasma membranes since these sites possesses an affinity with α – tocopherol. This tocopherol acts as antioxidants because of its ability to transfer to peroxyl free radical of peroxidized polyunsaturated fatty acid, a phenolic hydrogen, thereby, breaking chain reactions of free radical (Murray, et al., 1996). Tocopherol is regenerated following the reaction of the phenoxy free radical being formed with vitamin C. Additionally, chromane ring and side chain are also oxidized to a certain product that is non free radical as a result of more reaction with peroxyl free radical. At high concentration of oxygen, the antioxidant action of tocopherol becomes effective, and accordingly, it is expected that tocopherol is concentrated in lipid structures being exposed to the highest partial pressures of oxygen. An example for this is in the membrane of erythrocyte, respiratory tree, and retina (Murray, et al., 1996). Temple (2000) reported that an apparent 36 and 16% reduction of prostate and colorectal cancer, respectively, has been reported in ATBC Cancer Prevention Study with a dose of 50 mg/day. A partial regression of cancerous changes of the stomach has been observed by administration of 400 IU of Vitamin E per day, and at pharmacological doses (intake of several times more than US RDA of 8 – 10 mg per day), Vitamin E becomes anticarcinogenic (Temple, 2000). At a supplemental dose of 60 – 800 IU of Vitamin E per day, immune system in an elderly has reportedly improved (Temple, 2000). Evidence obtained from studies have shown that to prevent degenerative diseases and to preserve the function of the body even during the olden age, selenium and vitamin E are proven as safe, effective, and inexpensive (Temple, 2000 and Lippman, et al., 2005). IV. REFERENCES 1. Bairati, I., Meyer, F., and Gelinas, M. 2005. A Randomised Trial of Antioxidant Vitamins to Prevent Second Primary Cancers in Head and Neck Cancer Patients. Journal of the National Cancer Institute. 97(7): 481- 488. 2. Bjelakovic, G., Nikolova, D., Simonette, R., and Gluud, C. (2004). Antioxidant Supplements for Prevention of Gastrointestinal Cancers: A systemic review and meta – analysis. Lancet, 2004 (364): 1219 – 28. 3. Donaldson, M. 2004. Nutrition and Cancer: A review of the evidence for an anticancer diet. Nutrition Journal, 3(19): 1 – 21. 4. Eastwood, M. 1999. Interaction of Dietary Antioxidants in vivo: How Fruit and Vegetable Prevent Disease. Q J Med, 1999(1992): 527 – 530. 5. Huang, H., Alberg, A., Norkus, E., Hoffman, S., Comstock, G., and Helzlsour, K. 2003. Prospective Study of Antioxidant Micronutrients in the Blood and the Risk of Developing Prostate Cancer. American Journal of Epidemeology, 157(4): 335 – 344. 6. Key, T., Schatzkie, A., Willet, W., Allen, N., Spencer, E., and Travis, R. 2004. 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