Natural Powerful Antioxidants

US Pharm. 2007;1:HS38-HS42.

Antioxidants help protect human body cells from the formation of radicals. They comprise vitamins, minerals, enzymes, and natural products. Radicals, also known as free radicals, are molecules with one unpaired electron or two or more unpaired electrons that do not interact with one another. Oxygen-derived free radicals are aggressive and toxic and are produced typically during cell metabolism.¹ They are common transient intermediaries in chemical reactions with cell components, causing permanent damage. They are believed to be the source of aging and the cause of a number of degenerative diseases. In the human body, white blood cells interact with the free radicals, protecting body cells from harm.¹

Exposure to environmental perils, such as smoking, pollution, sun radiation, or other toxins, increases oxidative stress beyond a level at which the immune system can mount a defense. With increases in free radicals in the human body, the immune system's resources will be heavily involved in fighting free radicals. The ability of antioxidants to combat free radicals strengthens the immune system to identify and fight toxins.

There are three known free radicals: superoxide, hydroxyl, and peroxide. Antioxidants attach to the free radicals and form a complex that prevents cell destruction and is easily cleaned out as waste by the human body. The result is less cell damage and a healthier immune system, among other benefits.¹ This article reviews the major sources and roles of several antioxidants in the protection of human body cells to promote health and well-being.

Lycopene
The red pigmentation of foods such as tomatoes, pink grapefruit, guava, and watermelon is caused by the carotenoid lycopene. Research has shown that lycopene is a potent antioxidant that can help combat a number of diseases, including heart disease and cancer. Increased concentrations of lycopene provide greater protective effects; therefore, the most concentrated food sources, such as tomato paste and ketchup, are better protectors against these diseases.^1,2 Unfortunately, the human body is unable to produce lycopene and therefore must obtain this molecule from natural sources containing dietary carotenoids. Carotenoids are a family of natural pigments. There are more than 600 known natural carotenoids, all of which are biosynthesized only in plants.

Lycopene has a unique long-chain molecular structure containing 13 double bonds--more than any other carotenoid.² This configuration is responsible for lycopene's special ability to neutralize free radicals. Lycopene exists naturally in fresh fruits and vegetables in the trans-configuration, which is poorly absorbed. Heat processing of foods--for example, tomatoes processed into tomato paste, juice, or ketch­ up--induces the isomerization of lycopene from the trans- to cis-configuration. The cis-configuration has much better bioavailability.

Carotenoids are fat-soluble compounds; in the human body, they are found in fatty tissue and transported by lipoproteins. They act as dietary precursors to vitamin A and aid the immune system. Lycopene is also highly lipophilic and is commonly found within cellular membranes. It is a powerful antioxidant that can quench singlet-oxygen free radicals twice as efficiently as beta-carotene. Singlet oxygen is not a stable molecule but an unstable energy-rich form that is an aggressive radical.

Coenzyme Q₁₀
Coenzyme Q₁₀ (CoQ10), or ubiquinone, is essentially a vitamin or vitamin-like substance.³ It is found in small amounts in a wide variety of foods and is synthesized in all tissues. The biosynthesis of CoQ10 from the amino acid tyrosine is a multistage process requiring at least eight vitamins and several trace elements. CoQ10 is the coenzyme for at least three mitochondrial enzymes as well as enzymes in other parts of the cell. Mitochondrial enzymes of the oxidative phosphorylation pathway are essential for the production of the high-energy phosphate or adenosine triphosphate upon which all cellular functions depend. The electron and proton transfer functions of the quinone ring are of fundamental importance to all life forms.

CoQ10 has been the focus of scientific study for years and has become one of the most popular dietary supplements. It plays a crucial role in producing energy in cells. It acts as a powerful antioxidant, meaning that it helps neutralize cell-damaging molecules or free radicals. Manufactured by all cells in the body, CoQ10 is also found in small amounts in foods, notably meat and fish.

CoQ10 declines in the body as people age or develop certain diseases (such as some cardiac conditions, Parkinson's disease, and asthma). But that doesn't mean that lower levels of CoQ10 cause disease, or that supplemental CoQ10 will combat disease or reverse the effects of aging. Some drugs, including certain cholesterol-lowering statins, beta-blockers, and antidepressants, can reduce CoQ10 levels in the body, but there has been no evidence that this causes any adverse effects.

Researchers at the University of California, San Diego, found that very large doses of CoQ10 (along with vitamin E) appeared to slow the progression of Parkinson's disease. It reduced the decline in neurologic function and improved daily life. Because the study was small, the researchers determined that larger trials were needed before they could recommend CoQ10.

Most studies have used doses of 50 to 200 mg/day. But the new study on Parkinson's disease tested 300, 600, and 1,200 mg, with the largest dose having the greatest effect. Since CoQ10 is fat-soluble, it is probably best to take it with meals containing at least a little fat.³

Alpha-Lipoic Acid
Alpha-lipoic acid may very well join the ranks of vitamins C and E as part of the first-line of defense against free radicals. It was discovered in 1951 and serves as a coenzyme in the Krebs cycle and in the production of cellular energy. In the late 1980s, researchers realized that alpha-lipoic acid had been overlooked as a powerful antioxidant.⁴

Several qualities distinguish alpha-lipoic acid from other antioxidants. It neutralizes free radicals in both the fatty and watery regions of cells, in contrast to vitamin C (which is water soluble) and vitamin E (which is fat soluble). It is also a highly effective therapeutic agent in a number of conditions in which oxidative damage has a major role.⁵

The body routinely converts some alpha-lipoic acid to dihydrolipoic acid, which appears to be an even more powerful antioxidant. Both forms of lipoic acid quench peroxynitrite radicals, an especially dangerous type consisting of both oxygen and nitrogen. Peroxynitrite radicals play a role in the development of atherosclerosis, lung disease, chronic inflammation, and neurological disorders.⁶

In Germany, alpha-lipoic acid is an approved medical treatment for peripheral neuropathy, a common complication of diabetes. It speeds the removal of glucose from the bloodstream, at least partly by enhancing insulin function, and it reduces insulin resistance.

The therapeutic dose for lipoic acid is 600 mg/day in Europe. In the United States, it is sold as a dietary supplement, usually as 50-mg tablets. The richest food source of alpha-lipoic acid is red meat.

Ellagic Acid
Ellagic acid is a plant-derived polyphenol and a superantioxidant that inhibits hydroxyl radicals. It is mainly found in pomegranates. Pomegranates have been grown in Asia and the Middle East for millennia for spiritual as well as health reasons. Western medicine has only recently realized the importance of this superantioxidant, which is gaining popularity in the prevention and treatment of cancer and heart disease.⁷

The recent interest in the antioxidant power of pomegranates began primarily in 2000. Aviram et al. demonstrated the effectiveness of pomegranates in treating atherosclerosis by decreasing low-density lipoprotein cholesterol levels and increasing high-density lipoprotein cholesterol levels by up to 20% in humans.⁸ Their research has shown that consumption of pomegranate juice has significantly reduced the size of arterial plaque in both human subjects and mice.

Aviram et al. showed that pomegranate juice contains the highest antioxidant capacity compared with other juices, red wine, green tea, tomatoes, vitamin E, and other sources of antioxidants. Their research indicated that pomegranate juice contains at least three major antioxidants, and the juice has three times the antioxidant power of red wine or green tea.⁸

Ellagic acid itself is not thought to be naturally present in plants. Instead, polymers of gallic acid and hexahydroxydiphenoyl (HHDP) are linked to glucose centers to form the class of compounds known as ellagitannins. When two gallic acid groups become linked side by side within a tannin molecule, an HHDP group is formed. Ellagic acid is the result when the HHDP group is cleaved from the tannin molecule and spontaneously rearranges. It is the ellagitannins that are found in pomegranates.⁹

Recent scientific research is demonstrating that pomegranate may be helpful in the prevention and treatment of various types of cancer, such as prostate cancer. The juice has increased the prostate specific antigen doubling time in cancer patients with rising PSA after surgery or radiation. The research has found the positive effects of the juice on prostate cancer in in vitro cell proliferation and apoptosis as well as oxidative stress.⁷

Pomegranates not only are the richest source of ellagic acid but also contain anthocyanidins and proanthocyanidins (flavonoids)--substances that have been shown in animal and test tube experiments to reduce tumor angiogenesis.

Green Tea
Green tea has been consumed for centuries in India, China, Japan, and Iran, and in traditional Chinese and Indian medicine, it has been used as a stimulant (for somnolence), diuretic (to promote the excretion of urine), astringent (to control bleeding and help heal wounds), and to improve heart health. Other traditional uses of green tea include treating flatulence, regulating body temperature and blood glucose levels, promoting digestion, and improving mental processes.

There are three main varieties of tea--green, black, and oolong (Camellia sinensis). Green and oolong teas are more commonly consumed in Asian countries, while black tea is most popular in the U.S. The difference between the teas is in their processing. Green tea is prepared from unfermented leaves, oolong tea from partially fermented leaves, and black tea from fully fermented leaves. The more the leaves are fermented, the lower the polyphenol content and the higher the caffeine content. Polyphenols are chemicals that act as powerful antioxidants. Compared with black tea, green tea has a higher polyphenol content; however, black tea has roughly two to three times the caffeine content of green tea.¹⁰

Polyphenols contained in teas are classified as catechins. Green tea contains six primary catechin compounds: catechin, gallocatechin, epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate (also known as EGCG). EGCG is considered to be the most active component in green tea and is the best researched of all the green tea polyphenols. Green tea contains approximately 30% to 40% polyphenols, and black tea contains only 3% to 10% polyphenols. Green tea also contains alkaloids, including caffeine, theobromine, and theophylline. These alkaloids provide green tea's stimulant effects.¹⁰

In conclusion, tea flavonoids are potent antioxidants that are absorbed from the gut after consumption. Consistent tea consumption leads to a significant increase in the antioxidant capacity of the blood. Beneficial effects of increased antioxidant capacity in the body may be the reduction of oxidative damage to important biomolecules. The scientific support is strongest for the protection of DNA from oxidative damage after black or green tea consumption.¹⁰

Vitamin C
Vitamin C reaches every cell of the body, and the concentration of vitamin C in both blood serum and tissues is quite high. In fact, this nu­ trient plays a major role in the manufacture and defense of our connective tissue, the elaborate matrix that holds the body together. It serves as a primary ingredient of collagen, a glue-like substance that binds cells together to form tissues.

Vitamin C helps some of our most important body systems. First and foremost, it helps the immune system to fight off foreign invaders and tumor cells. In addition, vitamin C supports the cardiovascular system by facilitating fat metabolism and protecting tissues from free radical damage. It also assists the nervous system by converting certain amino acids into neurotransmitters.

The skin, teeth, and bones also benefit from vitamin C's collagen-forming and invader-resisting properties; this vitamin contributes to the maintenance of healthy bones, the prevention of periodontal disease, and the healing of wounds. It combats inflammation and pain by inhibiting the secretion of prostaglandins, which contribute to such symptoms.¹¹As a water-soluble antioxidant, vitamin C is in a unique position to "scavenge" aqueous peroxide radicals before these destructive substances have a chance to damage lipids. It works in collaboration with vitamin E, a fat-soluble antioxidant, and the enzyme glutathione peroxidase to stop free radical chain reactions. Vitamin C is an excellent source of electrons; therefore, it can donate electrons to free radicals, such as hydroxyl and superoxide radicals, and quench their reactivity.

Large concentrations of vitamin C can be found in fruits such as oranges, grapefruits, tangerines, lemons, and limes. Vitamin C and bioflavonoids--the water-soluble substances that help to protect human capillaries--are found in the white linings of these and other plants. Many vegetables also contain vitamin C, including tomatoes, broccoli, green and red bell peppers, raw lettuce, and other leafy greens.

Studies suggest that vitamin C's antioxidant mechanisms may help to prevent cancer in several ways. For example, vitamin C combats the peroxidation of lipids, which has been linked to degeneration and aging.¹² Vitamin C can also reduce the development of nitro­ samines from nitrates--chemicals which are commonly used in processed foods.

The recommended daily allowance of vitamin C is 120 mg. The tolerable upper intake is proposed to be less than 1 g/day.¹²

Vitamin E
Vitamin E is a fat-soluble vitamin that exists in eight different forms. Each form has its own biological activity, which is the measure of potency or functional use in the body. Alpha-tocopherol is the most active form of vitamin E in humans. It is also a powerful biological antioxidant. Vitamin E supplements are usually sold as alpha-tocopheryl acetate, a form that protects its ability to function as an antioxidant. The synthetic form is labeled "D, L" while the natural form is labeled "D." The synthetic form is only half as active as the natural form.

Studies are under way to determine whether vitamin E, through its ability to limit production of free radicals, might help prevent or delay the development of some chronic diseases such as cardiac diseases. Vitamin E has also been shown to play a role in immune function, DNA repair, and other metabolic processes.¹³

Selenium
Selenium is a trace mineral that supports healthy immune system activity, functions as a part of the potent antioxidant glutathione, and is necessary for good thyroid health.

Selenium is used by our bodies to produce glutathione peroxidase, a component of the body's natural antioxidant defense system that is manufactured in the liver. It works with vitamin E to protect cell membranes from damage caused by harmful free radicals and helps to detoxify harmful compounds in the liver. Additionally, some glutathione is released into the bloodstream, where it helps to maintain the integrity of red blood cells while protecting immune system white blood cells as part of the body's defense.¹⁴

In a study published in the American Journal of Clinical Nutrition, researchers investigated the effects of selenium and beta-carotene supplementation in patients who were known to have deficiencies of selenium and vitamin A.¹⁵ The researchers evaluated the blood enzymatic antioxidant system, including glutathione and selenium concentrations. Eighteen patients received no supplementation, 14 patients received oral selenium, and 13 patients received oral beta-carotene for a period of one year. Between three and six months, glutathione activity increased significantly in patients treated with selenium, compared with those treated with placebo. Only a slight increase was found following treatment with beta-carotene. The researchers stated that because glutathione plays an important role in the natural enzymatic defense system in detoxifying hydrogen peroxide in water, selenium supplementation could be of great interest in protecting cells against oxidative stress.

Because of the risk of toxic levels of selenium building up in the system, patients should avoid taking high doses--900 mcg or more at one time, or 600 mcg daily for an extended period of time. Patients must also be aware of the amount of selenium they take in from seafood, whole grains, oats, and nuts.¹⁴

The Role of the Pharmacist
Diets rich in antioxidants appear to reduce the risk of certain cancers, cardiac diseases, asthma, diabetes, and Parkinson's disease. Most of these antioxidants are affordable and readily available to anyone who wants them. Research indicates promising results on the protective effects of antioxidants to strengthen the immune system to fight toxins in human body.

Pharmacists are in an exceptional position to explain proper dosages to their patients and to clarify the roles of various synthetic and natural antioxidants available on the market. They can also explain the benefits patients receive from scavenging free radicals in their bodies to reduce cell and tissue damage.

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13. Khanna S, Roy S, Ryu H, et al. Molecular basis of vitamin E action: tocotrienol modulates 12-lipoxygenase, a key mediator of glutamate-induced neurodegeneration. J Biol Chem. 2003;278:43508-43515.

14. Thomson CD. Assessment of requirements for selenium and adequacy of selenium status: a review. Eur J Clin Nutr. 2004;58:391-402.

15. Hercberg S. The history of beta-carotene and cancer: from observation to interventional studies. What lessons can be drawn for future research on polyphenols? Am J Clin Nutr. 2005;81(1 Suppl):218S-222S.

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