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Antioxidants - Balancing Life: 02/2005

Life is all about balance and when balance is disturbed, life and health can be disturbed. Fortunately, nature provides for peaceful harmony in countless ways.

Jennifer Schraag
02/01/2005

References

An electron is a negatively charged atomic particle that can bond atoms together into molecules. With an instinct for stability, an electron craves to be paired with another electron. Often, an atom with an unpaired electron shares an electron with another atom (a covalent bond), forming a molecule. However, paired electrons in weakly bonded molecules can become unpaired when the molecule interacts with certain radical oxygen molecules. When such oxidation occurs, the once-bonded atom is transformed into a free radical, a highly reactive thief out to steal an electron from the nearest source. This free radical desperately seeks to restore balance, steals its necessary electron from the nearest neighboring source—forcing its victim to commit the same crime—and thus, the chain reaction of instability begins. The ensuing volatile reaction disrupts living cells, thus disrupting biochemical balance in the body.

Free radical reactions can bring death and destruction to proteins and cell membranes, weakening natural defense mechanisms and disrupting DNA cell formation. Continuous exposure to free radicals is a suspected key factor in the aging process. Oxidation is a regular occurrence in the body’s chemistry and many internal and external factors can affect free radical formation, but Mother Nature provides protection from these contributing factors—the natural scavenging gift of antioxidants.

Antioxidants are naturally occurring free radical scavengers that help protect the body from free radical destruction by hunting and neutralizing free radicals. They donate one of their own electrons, ending the destructive electron-”stealing” chain reaction occurring in the body. More interestingly, the antioxidant nutrients themselves do not become free radicals by this donation because antioxidants remain stable in either form.

Antioxidants work in several different ways to remedy free radicals. For example, some antioxidants work to reduce the energy of a free radical while others may stop a free radical by forming or simply interrupting an oxidizing chain reaction. Other beneficial activities of antioxidants include trapping free radicals and lipid peroxides, delaying the onset of lipid peroxidation, stalling production of free radicals and inhibiting the damaging effects of certain enzymes that can degrade connective tissues.¹

Antioxidants protect cells against the damaging effects of oxygen free radicals called reactive oxygen species (ROS)—singlet oxygen, superoxide, peroxyl radicals, hydroxyl radicals and peroxynitrite.² An imbalance between antioxidants and ROS results in oxidative stress that has been linked to not only aging but many degenerative diseases including heart disease, cancer and Alzheimer’s disease.³

Antioxidants are found within many natural dietary substances such as fruits, vegetables, teas and even chocolate. They also are produced naturally within the body. The best way to ensure adequate intake of antioxidant nutrients is by eating five to eight servings of fruits and vegetables per day.⁴ However, in an imperfect world, many consumers can use the boost of a range of antioxidants in supplemental form.

The Research Says It All

Retailers can arm their customers by educating themselves on the many different antioxidants already spanning their shelves and their beneficial effects.

Alpha-lipoic acid
(ALA) is a vitamin-like substance that is a very powerful natural antioxidant found in foods such as spinach and meats. ALA’s antioxidant activity includes free radical scavenging, metal chelating properties and the ability to reduce oxidative protein damage.⁵ Benefits of ALA also include boosting energy levels and reducing chronic fatigue, preserving memory and treating symptoms due to nerve and liver damage.⁶

ALA has been shown to have beneficial effects on polyneuropathy and on the parameters of oxidative stress in various tissues, including nerves, kidneys and retinas.⁷ Scientists have found long-term administration of ALA prevents development of diabetic retinopathy by inhibiting the accumulation of oxidatively modified DNA and nitrotyrosine in the retina. ALA also improves symptoms of diabetic peripheral neuropathy, according to Romanian researchers who also found ALA supplementation safe and efficient, and found it to improve clinical manifestations and nerve conduction velocity.⁸ ALA works to prevent diabetes mellitus by reducing lipid accumulation in non-adipose and adipose tissues, reducing body weight, lowering pancreatic islets, reducing triglyceride accumulation in skeletal muscle and protecting pancreatic beta-cells from destruction.⁹

R-Lipoic Acid
(RLA)/R-Dihydrolipoic Acid (R-DHLA) are oxidized/reduced forms of ALA that occur naturally as a pair in cells and have been widely characterized as antioxidants, according to David Carlson, Ph.D., molecular architect and director of research and development of Reno, Nev.-based GeroNova Research Inc. (www.geronova.com). “Many of their (RLA/R-DHLA) therapeutic effects act through prooxidant mechanisms by increasing the expression of genes regulating fat and carbohydrate metabolism and immune function,” Carlson said. “It is their ability to rapidly interconvert between prooxidant and antioxidant states according to the redox status of their local environment that makes them unique. They may induce genes and subsequently prevent build-up of excessive free radicals by maintaining them within a specific range before chain reactions gather momentum.”

Cosupplementation of ALA with the antioxidant CoQ10 (coenzyme Q10) reduces oxidative stress in the heart, thus inhibiting the aging process in the heart.¹⁰ CoQ10 is a potent antioxidant and a critical intermediate of the electron transport chain. CoQ10 may improve endothelial dysfunction by “recoupling” nitric oxide synthase (eNOS) and mitochondrial oxidative phosphorylation, and may act synergistically with anti-atherogenic agents—such as fibrates and statins—to improve endotheliopathy in diabetes.¹¹

The administration of CoQ10 to heart transplant candidates led to a significant improvement in functional status, clinical symptoms and quality of life in one study, leaving the scientists to conclude CoQ10 may serve as an “optional addition to the pharmacologic armamentarium” of patients with end-stage heart failure.¹² CoQ10 also is beneficial for use in renal transplant recipients, according to one Polish study,¹³ and those researchers went on to remark CoQ10 supplementation caused such statistically significant changes in the patients as decreased low density lipoprotein (LDL) and atherogenicity indicators and increased high density lipoprotein (HDL) levels.

CoQ10 supplementation provides a therapeutic benefit in patients with Huntington’s disease (HD) as well.¹⁴ The coenzyme reduces impaired mitochondrial function, which contributes to the neurodegenerative process in HD. CoQ10 also has significant antiaging functions,¹⁵ and improves vascular function while lowering blood pressure.¹⁶ CoQ10 aids other antioxidants when taken as dietary supplements, and it significantly enhances the antiinflammatory effects of vitamin E.¹⁷

Vitamin E
is a fat-soluble vitamin, and another known potent antioxidant. Vitamin E helps rid the body and skin of free radicals.¹⁸ Studies have shown a vast array of the beneficial effects of vitamin E including protective and healing effects for heart disease, cancer and cataracts.¹⁹ Vitamin E may also slow the progression of age-related memory loss;²⁰ and supplementation has been shown to improve immune response²¹ and possess a protective effect on upper respiratory tract infections, particularly the common cold, in the elderly.²²Alpha-tocopherol, one of the eight different forms of vitamin E, is noted to function as a major antioxidant in human LDL.²³

Another antioxidant within the vitamin realm is vitamin C. Vitamin C serves as a key immune system nutrient and a potent free radical fighter.²⁴ It is a water-soluble vitamin also known as ascorbic acid. Epidemiological studies show that diets high in vitamin C substantially cut the risk of most cancers and reduce stomach cancer risk by as much as 50 percent,²⁵ and subjects with higher supplemental vitamin C intake have demonstrated reduced incidence of major coronary heart disease (CHD) events.²⁶ Furthermore, researchers from the Mayo Clinic in Rochester, Minn. found long-term vitamin C supplementation increases NOS enzyme activity via chemical stabilization of tetrahydrobiopterin.

Minerals
, too, are encircled within this vast world of antioxidants. Dietary copper is an important mineral in oxidative defense. According to Colorado State University researchers, the impaired oxidative defense found in copper deficiency contributes to hypercholesterolemia, hypertension and impaired prostaglandin metabolism.²⁷ Dietary deficiencies of zinc contribute to single- and double-strand DNA breaks and oxidative modifications to DNA increasing the risk for cancer development.²⁸Selenium, too, has antioxidative effects and was proven effective in reducing cancer incidence in both animal and human models.²⁹ Observational and experimental studies have shown a higher selenium status reduces the risk of upper gastrointestinal cancers in selenium-deficient populations.³⁰ Iranian scientists, for example, found selenium deficiency plays a role in the high incidence of gastric cancer in the Ardabil Province in Iran due to the high levels of selenium deficiency in that area.

Countless herbs and botanicals have been used for the treatment of various human diseases throughout history and are well recognized for the role they play in disease prevention. The antioxidant properties of six medical herbs used in traditional Paraguayan medicine were recently studied using free radicalgenerating systems.³¹ The methanol extracts from Cecropia pachystachya, Eugenia uniflora, Schinus weinmannifolia, Schinus terebinthifolia, Piper fulvescens and Aristolochia giberti protected against enzymatic and non-enzymatic lipid peroxidation in the microsomal membranes of rats, and the first four showed the highest scavenging activity on the superoxide and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals.

Scientists examined the role of the Tibetan herbal formula Padma 28 in immune-related functions and found supportive results for the EcoNugenics® product Padma Basic®.³² The Austrian researchers reported Padma was found to effectively suppress the human body’s fluctuating levels of neopterin (an immune system marker) and tryptophan (a mood regulator). The scientists found the antioxidative properties of Padma are closely linked to the modulation of immunobiological events. “The ability of Padma to keep these immunobiological levels in check is an important finding in relation to the benefits that are found in the U.S. Padma formula,” said Isaac Eliaz, M.D., L.Ac, chairman of Santa Rosa, Calif.-based EcoNugenics (www.econugenics.com) and medical director of Amitabha Medical Clinic and Healing Center. Additional studies have suggested the Padma formula may be effective in supporting the immune system, promoting healthy circulation and improving cardiovascular and vein health.³³

Researchers also recently assessed the contribution of culinary and medicinal herbs to the total intake of dietary antioxidants and have noted more than a 1,000-fold difference among the antioxidant concentrations of various herbs.³⁴ Of the dried culinary herbs tested, oregano, sage, peppermint, garden thyme, lemon balm, clove, allspice and cinnamon, as well as the Chinese medicinal herbs Cinnamomi cortex and Scutellariae radix, all contained high concentrations of antioxidants (i.e., more than 75 mmol/100 g). The researchers noted a normal dietary intake of herbs may contribute significantly to the total intake of plant antioxidants.

Ginkgo biloba
extract may possess anticancer (chemopreventive) properties related to its antioxidant, anti-angiogenic and generegulatory actions as well as its ability to inhibit both inducible and endothelial forms of NOS. Exposure of human bladder cancer cells to a ginkgo extract produced an adaptive transcriptional response, in one study, augmenting its antioxidant status and inhibiting DNA damage.³⁵ Ginkgo extract aids in preventing radiation-induced cataracts in the lens of rats,³⁶ and inhibits the formation of radiation-induced clastogenic factors and ultraviolet light (UV)-induced oxidative stress. Ginkgo also can improve weight gain and mucosal healing in duodenal ulcer rats “by the actions of cytoprotection and antioxidation,”³⁷ and it reduces the symptoms of age-associated memory impairment and dementia—including Alzheimer’s disease.³⁸ Preliminary results also suggest ginkgo extracts may be useful in preventing and treating CVD—particularly ischemic cardiac syndrome.³⁹Panax Ginseng
(P. ginseng) is one of the most commonly used and researched of the ginsengs. P. ginseng, also called Asian or Korean ginseng, contains the main active component ginsenosides, which have been shown to have a variety of beneficial effects including anti-inflammatory, antioxidant and anticancer effects.⁴⁰ Clinical research demonstrates P. ginseng may improve psychological function, immune function, and conditions associated with diabetes.⁴¹ P. ginseng has continually been found to inhibit tumor growth— apparently mitigating cancer through anti-inflammatory, antioxidant, and apoptotic mechanisms to influence gene expression.⁴²

American ginseng berry extract protects cardiomyocytes against oxidant-mediated injury.⁴³ This protection is partly mediated by its free radical scavenging properties.

French maritime pine bark
(Pinus pinaster), is a potent antioxidant with multiple biological effects including antioxidant, antiinflammatory and anticarcinogenic properties. According to a University of California-Davis study, the extract as Pycnogenol® from Geneva-based Horphag Research (www.pycnogenol.com), significantly increases the antioxidant capacity of plasma, and exerts favorable effects on the lipid profile by significantly reducing LDL cholesterol levels and increasing HDL cholesterol levels.⁴⁴ Pycnogenol was found to lower blood glucose and improve endothelial function in Type II diabetic patients.⁴⁵ A recent African study demonstrated Pycnogenol treatment in diabetic rats significantly elevated levels of reduced glutathione and glutathione redox enzyme activities, altered intracellular antioxidant defense mechanisms, and elevated hepatic catalase activity was restored to normal levels.⁴⁶Carotenoids
, the naturally occurring lipid-soluble pigments found in a variety of plants, animals, algae and photosynthetic bacteria, are well known for their antioxidant values as well. Carotenoids possess the scavenging ability of free radicals and astaxanthin, canthaxanthin, beta-carotene and zeaxanthin, in particular, can suppress lipid oxidation.⁴⁷ Dietary beta-carotene has been shown to accumulate in the skin and act as a protective agent against UVAinduced oxidative damage,⁴⁸ and Japanese researchers found consumption of astaxanthin-producing marine animals inhibits LDL oxidation thus contributing to the prevention of atherosclerosis.⁴⁹Lycopene, lutein and zeaxanthin have antioxidative effects due to their rapid reactions of oxidizing agents.⁵⁰

Other antioxidative pigments include anthocyanins, the pigments found in several types of berries. Berries have been found to provide protection toward both lipid and protein oxidation.⁵¹ Wine, made from many berry species, is increasingly gaining recognition for its antioxidant values. Studies have found red wine to possess cardioprotective effects⁵² and acutely improve endothelial function in patients with coronary artery disease.⁵³ Phenolics from wine also may play a positive role against LDL oxidation.⁵⁴

The antioxidant activity of berry phenolics includes not only the anthocyanins, but proanthocyanidins. Grape seed extract (GSE) is a powerful antioxidant found to protect the body from premature aging, disease and decay.⁵⁵ Grape seeds contain proanthocyanidins, which have been shown in scientific studies to have antioxidant power 20 times greater than vitamin E and 50 times greater than vitamin C.⁵⁶ Further research suggests that GSE is beneficial in many areas of health because of its ability to bond with collagen— promoting youthful skin, cell health, elasticity, and flexibility. Further supporting its skin care abilities, Japanese researchers found GSE effective in reducing the hyperpigmentation of women with chloasma (melasma), an acquired hypermelanosis.⁵⁷ In their study, GSE was found safe and useful for improving the condition and GSE intake for five months showed preventive effects when taken prior to the summer season. In addition, the scientists found the beneficial effect of GSE maximally achieved after six months.

The proanthocyanidins found in GSE also help protect the body from sun damage, improve vision, improve flexibility in joints, arteries and such body tissues as the heart, and they improve blood circulation by strengthening capillaries, arteries and veins.⁵⁸ Studies also show GSE protects from ischemic neuronal damage by inhibiting DNA damage after transient forebrain ischemia,⁵⁹ has the potential to favorably influence vascular function⁶⁰ and may protect against cardiac ischemia and reperfusion injury.⁶¹

Chocolate
is produced by the cocoa plant Theobroma cacao. Chocolate is rich in flavonoids which, among many other benefits, have been found to act as antioxidants inhibiting ROS- and Reactive Nitrogen Species (RNS)-caused brain damage.⁶² Recent evidence also shows flavanol-rich cocoa activates vascular eNOS, signaling the possibility of a therapeutic potential. “Endothelial dysfunction is widely accepted as an important element in cardiovascular risk,” said Norman Hollenberg, Ph.D., professor of medicine at Brigham and Women’s Hospital in Boston, and lead author of a review focusing on cocoa’s benefits. “While we know many things reduce endothelial function, such as smoking, there are few agents or approaches that improve endothelial function consistently. The striking influence of flavanol-rich cocoa on nitric oxide-dependent endothelial function offers promise of a new approach to therapy.” Cardioprotective effects—including inhibition of platelet activity and activation of eNOS—have been ascribed to cocoa flavonoids. Studies show consumption of chocolate reduces the production of free radicals in fecal water⁶³ and increases the concentration of HDL cholesterol.⁶⁴ Dark chocolate, especially, improves endothelial function⁶⁵ and increases blood antioxidant levels.⁶⁶

Chocolate is also rich in polyphenols. Polyphenols are potential agents in inhibiting the oxidation of LDL cholesterol,⁶⁷ and consumption of polyphenol-rich foods, such as fruits and vegetables, and beverages derived from plants—such as cocoa, red wine and tea—may represent a beneficial diet in terms of cardiovascular protection. One study, comparing the phenolic and flavonoid contents and total antioxidant capacities of cocoa, black tea, green tea and red wine declared cocoa the winner and most beneficial to health citing a higher antioxidant capacity.⁶⁸

Green tea
polyphenols have both antioxidant and antiinflammatory properties. Green tea polyphenols reduce the severity of liver injury in association with lower concentrations of lipid peroxidation and proinflammatory nitric oxide-generated mediators.⁶⁹ Green tea polyphenols can be a useful supplement in the treatment of liver disease and should be considered for liver conditions in which proinflammatory and oxidant stress responses are dominant, according to researchers from the Lerner Research Institute in Cleveland.⁷⁰ Green tea polyphenols—in particular, the putative novel neuroprotective mechanism of the major green tea polyphenol, (-)- epigallocatechin-3-gallate, (EGCG)—are considered therapeutic agents in well-controlled epidemiological studies, aimed to alter brain aging processes and serve as possible neuroprotective agents in progressive neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases,⁷¹ and EGCG also has a potent free radical scavenging and antioxidant effect which may be used as a neuroprotective agent against additional neurologic disorders such as brain ischemia.⁷²Black tea
polyphenols significantly inhibited rat ovarian and human placental aromatase activities, leaving the researchers to conclude black tea polyphenols may be beneficial in the chemoprevention of hormone-dependent breast tumors and represent a possible remedy to overcome hormonal resistance of hormone-independent breast tumors.⁷³ Furthermore, black tea demonstrated beneficial antioxidant effects on the liver.⁷⁴

With the vast realm of available antioxidants, retailers may educate their customers, help them embrace the idea that free radicals may well be the aging enemy and explain how future antioxidant supplementation will aid in the preservation of health and slow the onset of age-related diseases.

February 2005 Health Supplement Retailer
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