Avoiding the Redox Landslide

Natural antioxidant ingredients improve health by stifling oxygen-induced electron transfer

References

SIDEBAR:  Investigating ORAC

Antioxidant health products have some pretty origins. Colorful vegetables and fruits, including more recently touted exotic varieties, are the usual sources, not to be outdone by cocoa, coffee, tea and various herbs. But their antioxidant mechanisms are essentially the same biochemically—stopping free radical oxygen byproducts from stealing electrons and victimizing another important molecule. This protection against oxidation is necessary in every part of the body, including the heart, blood vessels, brain, lungs, eyes, liver and kidneys. Each natural antioxidant compound seems to work against certain reactive oxygen species (ROS) in certain parts of the body, but not in others.

On the surface, normal living and aging doesn’t seem so radical; but, invisibly to the eye, highly reactive free radicals can levy some hefty damage. These volatile molecules have an unpaired electron in their outer shell, so they steal an electron from a nearby molecule. Like a vampire bite, losing an electron to a free radical can turn the victim into a radical, creating the potential for cascading damage to healthy cells. Oxidation has been found to contribute to the development and progression of numerous degenerative diseases, including cardiovascular disease (CVD), diabetes, cancer, Alzheimer’s disease and various retinal conditions.

Like death and taxes, oxidation is a fact of life. Life needs oxygen, but the element is highly reactive. Plants and animals have adapted to this by manufacturing endogenous antioxidant compounds that can nullify the thievery of existing radicals or inhibit the formation of new ones.

The difference between an antioxidant and any other molecule that tangles with ROS is the antioxidant can neutralize the radical yet remain stable itself. This process of oxidation and anti-oxidation occurs in the human body countless times every day, as one of the key process of forming ROS superoxide anion involves the metabolism of energy, specifically the electron transport chain.

But modern is life harsh, and pollution, poor eating habits, increased stress and environmental conditions have created more free radicals than the human body can handle on its own. The two main solutions for this growing concern are to increase production and capacity of endogenous antioxidants, or supplement with antioxidant compounds from nature.

Among the body’s endogenous defenses against ROS are glutathione peroxidase (GPx) enzymes, which target lipid hydroperoxide and hydrogen peroxide. One way to improve GPx production is by increasing vegetable and fruit intake.1 Also, GPx is a selenium-containing compound, and supplemental selenium can help support GPx activity. GPx also relies on the amino acids glutamine, cysteine and tryptophan, and these amino acids are theorized as useful in conditions marked by GPx-deficiency, especially AIDS (acquired immune deficiency syndrome).2 In a 2004 review paper, University of Victoria, British Columbia, scientist Harold Foster, Ph.D., noted physicians involved in a selenium and amino acid field trial in Botswana reported a 99-percent AIDS reversal rate in patients taking this nutritional protocol, with improvements occurring in as few as three weeks.3

Another endogenous oxidation fighter is superoxide dismutase (SOD). As its name implies, this enzyme targets superoxide, breaking it down to hydrogen peroxide and oxygen. Superoxide is used in a positive way by the immune system to squash microscopic pathogens, but it can also inactivate certain enzymes that control free iron, which can lead to formation of hydroxyl free radical.

Fortunately, SOD is a formidable and swiftly acting foe of superoxide. As a way of gauging the importance of various SOD forms—including manganese-dependent (MnSOD) and copper-zinc-dependent (CuZnSOD)—scientists “knock out” a specifc SOD form in culture or animals. Results of these trials have revealed MN-SOD knockout in tissues correlates to increased mortality, cognitive degeneration and caridomyopathy, whereas CuZnSOD knockout can result in increased risk of cancer, infertility and vascular diseases.^4,5,6,7 SOD supplementation (as GliSODin®, from P.L. Thomas & Co.) has been found to protect DNA from oxidative damage in subjects exposed to accelerated oxidative stress via a hyperbaric chamber.⁸

Specifically, results showed those given SOD had fewer DNA strand breaks and lower serum levels of isoprostane (lipid peroxidation marker) than subjects given placebo. Other research discovered GliSODin administration to mice promoted cellular antioxidant status and produced an increase in blood antioxidant activities, correlating with an increased resistance of red blood cells to oxidative stress-induced cell death.⁹

What’s good for the blood is good for the skin, as GliSODin most recently demonstrated significant protection against oxidative damage from ultraviolet (UV) radiation exposure in a multi-center French trial.¹⁰ UV skin burn (actinic erythema) was induced on the inner-forearms of 49 healthy subjects who then supplemented with GliSODin or a placebo for four weeks. Those taking SOD had increases in the minimum exposure to UV rays necessary to produce skin burn. The scientists wrote: “This study confirms the efficacy of GliSODin in the prevention of the consequences of oxidative stress resulting from exposure to the sun. This efficacy is of particular interest for phototypes II (fair-skinned) that represent a major part of the consultations in dermatology.”

Exercise creates an abundance of free radicals, and SOD may counteract the oxidative damage common to rigorous workouts, according to a study from Peking University.¹¹ Results from the trial showed administration of SOD in rats limited oxidative damage to muscles induced by muscle strain and facilitated muscle regeneration.

Yet another endogenous antioxidant compound is the hormone melatonin, which is well-known as a sleep cycle component, but actually scavenges free radicals quite well, especially in brain tissue. Not only does melatonin combat oxidative stress in the hippocampus by increasing tissue levels of GPx, SOD and catalase (CAT) and other antioxidant enzymes,¹² but it also protects the brain from oxidative stress common in Parkinson’s disease by scavenging hydroxyl radicals in the mitochondria, reversing glutathione depletion and restoring SOD and CAT activities.¹³ Protecting these antioxidant enzyme activities is also key to melatonin’s protection of liver cells from oxidative stress, according to a study on pancreatic disease.¹⁴

The idea of chemical antioxidants was known in the late 19th and early 20th centuries, but the theory of free radical aging was discovered by Denham Harmon, M.D., Ph.D., in the 1950s. At the time, certain antioxidant compounds, including vitamins C and E, were already known, but their benefits to human health were not really studied widely until the 1960s. Since then, work on these vitamins has produced great health discoveries.

Vitamin C is among the group of water-soluble antioxidants able to scavenge aqueous peroxyl radicals. While this vitamin has shown promising protective activity against oxidation in brain tissue and the eyes,^15,16 as well as a foil for oxidative stress relative to CVD,¹⁷ it has been extensively studied in cases of exercise-induced oxidative stress.¹⁸

A Taiwanese study found insufficient vitamin C status correlated to low serum concentrations of lipid peroxides and increased muscle damage in female weightlifters undergoing intensive resistance training.¹⁹ A Spanish study found vitamin C supplementation in volunteer endurance athletes increased erythrocyte antioxidant enzymes and plasma antioxidant levels during athletic competition and short-term recovery.²⁰ On the contrary, athletes taking placebo experienced increased serum markers of oxidative stress, including uric acid and lactate dehydrogenase. In 2006, University of North Carolina, Greensboro, researchers found vitamin C pretreatment (3 g/d, two weeks before rigorous exercise) can reduce muscle soreness, delay creatine kinase increase and prevent blood glutathione oxidation, with little influence on muscle function loss.²¹

Oxygen consumption by the skeletal muscle can increase 100 to 200 times during endurance exercise, which can deplete vitamin E and increase lipid peroxidation. A randomized, double blind study in runners participating in an ultra-marathon race showed supplementation with both vitamins E and C prevented increases in lipid peroxidation, but had no apparent effect on DNA damage, inflammation or muscle damage.²² However, vitamin C is theorized to protect and even rejuvenate vitamin E. Studies using combinations of these two antioxidant vitamin pioneers have demonstrated health benefits against lipid peroxidation.

Researchers from Wake Forest University School of Medicine trial reported rats on a diet containing 2,000 mg/kg vitamin C plus 1,000 IU/kg vitamin E for two weeks tested for reduced markers of oxidative stress following 90 minutes of exercise on an inclined rodent treadmill.²³ Lipid peroxidation is also a major factor in CVD, and increased oxidative stress is a major consequence of habitual smoking. Based on these premises, the 2003 Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study investigated twice-daily supplementation with a combination of 250 mg slow-release vitamin C and 136 IU of vitamin E in 520 smoking and nonsmoking men and postmenopausal women aged 45 to 69 years and with elevated cholesterol levels.²⁴ They found the antioxidant combination slowed atherosclerotic progression in hypercholesterolemic subjects. In 2006, Oregon State University, Corvallis, scientists shed light on the possible synergy between vitamins C and E in smokers.²⁵ Their double blind, placebo-controlled, randomized crossover investigation in smokers revealed rapid disappearance of both alpha- and gamma-tocopherol levels in smokers, a depletion credited to oxidation of the vitamin E forms. However, vitamin C supplementation doubled the levels of these tocopherols in smokers, but not in non-smokers, presumably via reduction of the tocopherol radicals back to their stable form.

Vitamin E has conferred CVD-related antioxidant benefits on its own. Adding to its benefits to CVD, vitamin E has been shown to inhibit lipid peroxidation of low-density lipoprotein (LDL) cholesterol and/or atherosclerosis in a handful of clinical trials.^26,27,28 It also has limited oxidative stress in hypertensive, but not normotensive, animals.²⁹ More recently, a study on serum antioxidants and total antioxidant reserve (TAR) on coronary artery disease (CAD) in people with type 2 diabetes—especially those with renal complications—found alpha-tocopherol showed some protective benefit against CAD among antioxidant supplement users and those with renal disease, but not among non-antioxidant users.³⁰

Tocotrienols, another form of vitamin E, have also left their antioxidant mark on oxidative stress. Two National Institutes of Health (NIH)-funded studies examined tocotrienols’ (as Tocomin®, from Carotech) effect against neurological maladies marked by oxidative damage. One study, Ohio State University Medical Center, Columbus, demonstrated how pretreatment with tocotrienols in animals with low vitamin E levels helped to inhibit cell damage from induced toxicity.³¹ However, researchers noted reduction of free radical activities was only achieved when tocotrienol concentration was raised between 10 to 25 times the levels that protected against cell death.

In the other study, Wayne State University, Detroit, scientists gave women with normal cholesterol levels 400 mg of tocotrienol softgels and then gave them an oral fat challenge (lipid load).³² Supplementation significantly increased plasma tocotrienol levels, peaking between 12 and 30 times more than the concentration required to prevent stroke-related neurodegeneration (as determined by earlier research).

In another brain health study, researchers at Rush-Presbyterian- St. Luke’s Medical Center used food frequency questionnaires to monitor dietary habits of approximately 3,000 volunteers aged 65 to 102 years old, measuring cognitive aptitude at baseline and at the end of the study.³³ Results showed a higher intake of total vitamin E, from both foods and supplements, was associated with a reduction in cognitive decline.

And similar to vitamin C’s effect on exercise, a double blind, placebo-controlled study in 14 male runners found vitamin E supplementation attenuated increases in serum markers of oxidative damage (creatine kinase and lactate dehydrogenase) following six days of endurance running.³⁴

There is much debate on the best form of vitamin E, and research has not cleared up the picture much. A published study (Soft Gel Technologies) of alpha-tocopherol, mixed tocopherols and mixed tocotrienols individually or in various combinations (delivering 400 IU of vitamin E) found powerful antioxidant capabilities for each intervention, but the combinations more often outperformed individual alpha-tocopherol in antioxidant actions.³⁵ On the other hand, a University of Perugia, Italy, study on prostate cancer cell proliferation compared the efficacy of alpha-tocopherol and gamma-tocopherol, as well as their respective metabolites (alpha- and gammacarboxyethyl hydroxychromans), with Trolox® (a vitamin E analogue from AlexisCorp.) and alpha-tocopherol succinate; results showed gamma-tocopherol to be the most effective antioxidant treatment.³⁶

Like vitamin E, coenzyme Q10 (CoQ10) is a lipophilic antioxidant that fights lipid radicals and is even considered vitamin-like due to depletion in older people. Its crucial role in the electron transfer chain makes CoQ10 an important antioxidant against mitochondrial radical formation, namely superoxide. Research has focused on CoQ10 in CVD. At the center is its ability to protect heart cell mitochondria from oxidative stress and damage.^37,38 Head-to-head with CVD in animal research, CoQ10 supplementation (as Q-Gel®, from Tishcon) has reduced markers of oxidative damage and inhibited development of atherosclerosis.³⁹ Human study has born similar results. A Polish trial involving 60 mg/d CoQ10 supplementation for eight weeks in heart patients positively modified oxidative stress, antiatherogenic fraction of lipid profile, atherogenic ratio and platelet aggregation.⁴⁰ As evidence of the other mechanism of antioxidant supplementation, a Russian study found CoQ10 increases resistance to oxidative stress in the myocardium not only by direct antioxidant activities on radicals, but also by increasing activity of endogenous antioxidant enzymes.⁴¹

Another vitamin-esque compound, alpha lipoic acid (ALA), is considered frontline antioxidant defense. Discovered in the 1950s, ALA also acts as a coenzyme in the cellular energy cycle. While a hydrophilic antioxidant, ALA can scavenge free radicals in both watery and fatty regions of cells, giving it potentially broad health benefits.

ALA has a particularly renowned effect on peroxynitrite radicals, which have been implicated in the development of atherosclerosis, lung disease, chronic inflammation, and neurological disorders.

An animal study conducted at Annamalai University, India, examined ALA-mitigated fructose-induced oxidative stress in heart tissue.⁴² Researchers noted ALA raised serum antioxidant levels in addition to reversing increased peroxidation, impaired antioxidant status and lipid abnormalities in the cardiac tissue. Further, a University of Madras, Chennai, study found co-administration of ALA and L-carnitine (which is involved in electron transport) protected against oxidative damage in the heart by reversing age-related decline of a component of the endogenous GPx function in older rats.⁴³

In 2007, ALA has made its antioxidant impact on eye, brain and sexual health. Based on the link between brain damage and chronic exposure to arsenic (a common environmental toxin found naturally in groundwater), researchers from Cheng Kung University, Taiwan, studied the neuroprotective effects of ALA on toxicity in glial cells— non-neuronal cells that provide nutrition, ensure balance, form myelin and participate in signal transmission in the brain.⁴⁴ Results showed ALA completely attenuated arsenic-related cell death while demonstrating potential to reverse arsenic-induced brain damage.

A known source of oxidative stress and damage, smoking has been studied for its damage to retinal pigment epithelial (RPE) cells and its reaction to ALA supplementation. Researchers at Children’s Hospital Oakland Research Institute, Calif., tested the major cigarette toxin acrolein in human RPE (ARPE-19) and human fetal RPE (hfRPE) cell cultures; pretreatment with ALA was performed in another stage of the trial.⁴⁵ Results revealed acrolein is a mitochondrial toxicant in both ARPE-19 and hfRPE cells, causing oxidative damage that can be inhibited by ALA pretreatment.

ALA also conveys protective antioxidant benefits in cases of spermatic cord torsion—the twisting of the cord housing nerves, blood vessels and the vas deferens, which cuts off blood flow to the testicles.

A Brazilian study reported ALA administration prior to cord torsion reduced testicular oxidative damage markers while rejuvenating glutathione and plasma total antioxidant concentrations—which had been depressed after torsion-like ischemis induction and reversal.⁴⁶

It is no surprise the two mitochondrial protectors ALA and CoQ10 would be a good antioxidant combination treatment. University of Pennsylvania School of Medicine, Philadelphia, researchers evaluated the protective effects of these two antioxidants and other compounds against radiation-induced oxidative stress in cultured human epithelial cells exposed to radiation from X-rays and other sources.⁴⁷ They reported CoQ10 and ALA—along with cysteine, vitamin C, vitamin E succinate and selenium—helped protect against oxidative damage generated by the radiation exposure.

Endogenous enzymes and the compounds that support them are endless fodder for health researchers. In the case of selenium, support of GPX and another antioxidant enzyme, thioredoxin, has been pegged as the mechanism behind the antioxidant mineral’s ability to decrease the risk of certain cancers, especially those of the prostate, lung and colon.^48,49 This type of role also contributes to selenium’s protection of the heart. An Italian study in rats revealed selenium administration increased total antioxidant activity, glutathione concentration, and glutathione peroxidase and catalase activities leading to a decreased generation of reactive oxygen metabolites.⁵⁰

Fellow mineral zinc, which plays a role in CuZnSOD, might also deliver antioxidant benefits via support of endogenous enzymes. A Panjab University, India, study suggested zinc supplementation protects red blood cells from oxidative damage by attenuating the effects of radiation on endogenous antioxidant enzymes, including SOD.⁵¹ Zinc is another prostate-friendly mineral, as researchers have correlated increased lipid peroxidation with decreased SOD activity and low zinc levels in men with benign prostatic hyperplasia (BPH).⁵²

Increased dietary intake of zinc—along with the antioxidants vitamin C and E and beta-carotene—was linked to reduced risk of age-related macular degeneration (AMD) in elderly subjects, although there was no specific antioxidant mechanism indicated in the 2005 JAMA report.⁵³

As two heads are often thought better than one, combination antioxidant supplementation has garnered much attention, both positive and negative.

In 2006, researchers from Firat University, Turkey, reported a combination of melatonin and vitamin E might reverse cognitive damage related to diabetes.⁵⁴ Diabetic rats suffered cognitive decline accompanied by increased lipid peroxidation and decreased GPx in the hippocampus and frontal cortex. Pretreatment with the vitamin-hormone combination reversed these oxidative effects, improving learning and memory to near control levels. And in a 2006 Australian trial, vitamin E and ALA improved GPx and CAT activities in exercise-trained animals better in combination than as individual compounds.⁵⁵

Despite these positive results, a 2007 JAMA report concluded antioxidants not only failed to show benefit to all-cause mortality, but they appeared to increase the risk of mortality.⁵⁶ Of the antioxidants reviewed by Dutch scientists, beta-carotene, vitamin A and vitamin E supplements were linked to increases in risk of mortality of 7 percent, 16 percent and 4 percent, respectively. The antioxidant supplementation in general correlated to a 5-percent increased risk of mortality, and researchers noted the roles of vitamin C and selenium require further studies. Supplement industry experts criticized the combination of vastly different studies in this meta-analysis, calling the results compromised.

Still, antioxidant combinations continue to log positive research results against oxidative degeneration. A pair of studies published in 2007 detailed the protection antioxidants provide against degeneration from exposure to light and the elements. German scientists reported supplementation with vitamin E, selenium and carotenoids (lutein, lycopene and beta-carotene) improved skin roughness, scaling and wrinkling.⁵⁷ And a Spanish study found lutein, zeaxanthin, ALA and glutathione had no rescue effect on retinal photoreceptors, but did slow down photoreceptor degeneration when administered in combination to rats with oxidative damaged rods.⁵⁸

Carotenoids, including lutein, zeaxanthin, astaxanthin and lycopene, are the colorful pigments found in various plants. As a group, these antioxidant compounds have shown protective effects against development of cancer, especially colorectal adenomas,^59,60 toxic damage to the liver,⁶¹ and free-radical-induced atherosclerosis progression.⁶²

Working off this premise, researchers studied lycopene-rich tomato extract (as Lyc-O-Mato, from LycoRed) on blood pressure and oxidative markers in hypertensive patients.⁶³ After taking 250 mg/d Lyc-O-Mato for eight weeks, thiobarbituric acid-reactive substances (lipid peroxidation markers) were decreased, as were both systolic and diastolic blood pressure readings. Subsequent study of this extract on cellular antioxidant protection resulted in lymphocytes subjected to oxidative stress.⁶⁴ And most recently, a pair of dermatological studies on Lyc-O-Mato revealed protective benefits against premature skin aging from sun exposure. In one trial, University of Düsseldorf, Germany, researchers reported Lyc-O-Mato decreased the reddening of the skin of the participants, indicating protection from UV-induced damage; they noted synthetic lycopene showed only a 25-percent reduction in redness, whereas Lyc-O-Mato led to a 38-percent reduction.⁶⁵ In the other study, subjects receiving one of two different levels of a mixture of lycopene, lutein, beta-carotene, alpha-tocopherol and selenium experienced a significant increase in skin density and thickness, improvement in skin smoothness and softness and reduced scaling, compared to those in the placebo group.⁶⁶

Other carotenoids have concentrated protection in the eyes. In fact, the connection between retinal protection and lutein and zeaxanthin is based in the macular pigment, which contains healthy amounts of each carotenoid. Supplementation with lutein and zeaxanthin may prevent retinal degeneration via protection from damaging sunlight.⁶⁷

In one trial, 90 patients with atrophic AMD, characterized by oxidative damage, who supplemented for 12 months with 10 mg/d lutein (as FloraGLO® Lutein, from Kemin Health) alone, or in conjunction with abroad spectrum antioxidant formula including vitamins and minerals, showed improved visual function.⁶⁸ Additional research out of the University of Manchester, England, found administration of 20 mg/d lutein ester (as Xangold®, from Cognis), equivalent to 10 mg/d free lutein, benefited patients with early AMD by increasing macular pigment optical density (MPOD) and plasma lutein concentrations.⁶⁹ The researchers concluded a diseased macula can accumulate and stabilize lutein and/or zeaxanthin, and lutein supplementation may even help patients in a more advanced stage of macular disease.

The eyes also spy astaxanthin when in need of protection from lipid peroxidation and oxidative stress related to cataract development. An Ohio State University, Columbus, study showed pretreatment of human lens epithelial (HLE) cells with astaxanthin, along with fellow xanthophylls lutein and zeaxanthin, before UVB radiation exposure resulted in decreased lipid peroxidation and oxidative stress markers, compared to alpha-tocopherol treatment, which required substantially high amounts to approach equivalent protection.⁷⁰ Similarly, an Italian study found these three carotenoids have similar superoxide-scavenging activity in the human retina, relative to superoxide and hydrogen peroxide, in addition to varying degrees of DNA protection and repair during UVA radiation exposure, depending upon time and cell type exposed.⁷¹

Besides carotenoids, plants contain numerous polypenols with antioxidant properties. Various vibrant fruits owe their rich colors and antioxidant properties to certain flavonoids, including anthocyanidins and proanthocyanidins. Grapes contain both these flavonoids, as well as resveratrol, all of which have been credited with the fruit’s antioxidant benefits. A study presented in late 2006 by researchers from the Preventive Cardiology Program, Davis Medical Center, Sacramento, Calif., showed one month of grape seed extract (GSE) supplementation (as MegaNatural® BP, from Polyphenolics), in either 150 mg/d and 300 mg/d dose, significantly reduced blood pressure; those taking 300 mg/d of MegaNatural BP had a significant decrease in the concentration of oxidized LDL in plasma.⁷²

Tests of hepatocarcinoma cell line HepG2 treated with doses of grape procyanidins between 0 mg/L to 100 mg/L for 24 hours revealed a 15 mg/L dose regulated glutathione-related antioxidant enzymes by increasing both in mRNA and in enzyme activity levels; in cells subjected to oxidative stress (hydrogen peroxide), GS procyanidins increased mRNA GPx.⁷³ Researchers concluded GS probably improves the cellular redox status via glutathione synthesis pathways instead of regulation of the GPx activities protecting against oxidative damage.

The antioxidant properties of grapes are thought to transfer to wine, which has shown numerous protective benefits to cardiovascular health. However, a 2006 study linked wine’s antioxidant actions to other organs commonly afflicted by oxidative stress. Spanish researchers administered 400 ml/70 kg/d of red wine and a high-cholesterol diet (1.65-percent cholesterol) to rats and monitored levels of brain and kidney oxidative stress, as well as antioxidant enzyme activity.⁷⁴ They found total cholesterol and lipid peroxidation products in the brain, kidney and erythrocytes decreased significantly, while glutathione content and antioxidant enzyme activities increased.

In other neurological research on grape products, a University of Madras, Chennai, India, animal trial found GSE may improve antioxidant status and limit free radical-induced protein oxidation, thereby protecting the central nervous system from ROS.⁷⁵ Another animal trial from this research facility found GSE protected the brain from oxidative damage by inhibiting free radical-induced lipid peroxidation.⁷⁶

Proanthocyanidins and anthocyanins are also abundant in various berries, which have demonstrated potent antioxidant capabilities in many areas of human health, including CVD, cancer, cognitive stability and eye health.

Anthocyanin glycosides are absorbed in the stomach and the intestines, according to studies on blackberries and bilberries;^77,78 and despite having a low bioavailability, bilberry anthocyanins quickly boost plasma antioxidant capacity.⁷⁹ Additional data proves blackberry anthocyanins cross the blood-brain barrier.⁸⁰

In 2002, Jess Reed, Ph.D., from the University of Wisconsin, Madison, recognized the potential application of cranberry flavonoids in reduction of lipid peroxidation in atherosclerosis and CVD.⁸¹Blueberries possess similar properties, as evidenced by results from a 2000 trial at Jean Mayer Human Nutrition Research Center on Aging at Tufts University, which showed the fruit’s polyphenols, including anthocyanins, inhibited ROS formation within red blood cells in vivo.⁸²

These two berries are a part of a six-berry extract (OptiBerry, from InterHealth Nutraceuticals), which has demonstrated an ability to inhibit hydrogen peroxide and angiogenesis in a study on antioxidant capacity and anti-cancer benefits.⁸³ A subsequent study on this extract—which contains wild blueberry, bilberry, cranberry, elderberry, raspberry seeds and strawberry—revealed eight weeks of supplementation in animals impeded glutathione oxidation in lung and liver tissue exposed to hyperbaric oxygen.⁸⁴

Recently, another fruit blend including raspberry, prune, pomegranate, blueberry, grape and strawberry—called Radical Fruits™, from Garden of Life—was the subject of a randomized, double blind, placebo-controlled trial on blood and urine oxidation markers.⁸⁵ Hypercholesterolemic subjects taking 900 mg Radical Fruits three times daily for four weeks had reduced plasma total cholesterol, increased HDL cholesterol and decreased urinary oxidative markers, including isoprostanes.

Pomegranate contains numerous flavonoids and other antioxidant phytochemicals that have delivered positive results in various oxidative-related health conditions. Among its possible antioxidant mechanisms, pomegranate extract reduced the activation of certain oxidation-sensitive genes in a model of shear stress, in addition to reducing isoprostane in hypercholesterolemic mice.⁸⁶ Adding to the knowledge, UCLA researchers reported in late 2006 on pomegranate juice’s potent activity against oxidative destruction of nitric oxide, which is crucial in many areas of health, especially those involving vascular function.⁸⁷

Pomegranate antioxidant phenols are also neuroprotective, although the exact mechanism behind its reduction of amyloid load in Alzheimer’s disease is not determined.⁸⁸ However, Chinese scientists recently clarified the actions of specific parts of pomegranate fruits, explaining red pomegranate peel was the best scavenger of superoxide anion, whereas white pomegranate seed best scavenged hydrogen peroxide and, of nine pomegranate parts tested, showed the greatest protection against DNA damage.⁸⁹ The fruit’s action in CVD is a bit more clear, as Israeli researchers have discovered administration of pomegranate to lipoprotein-E-deficient mice limits atherosclerosis by reducing oxidative stress in macrophage cells.⁹⁰ Meanwhile, Italianscientists found pomegranate polyphenols curbed atherosclerosis by lowering oxidative stress in human endothelial cells exposed to high shear stress both in culture and in hypercholesterolemic animals.⁹¹

A new antioxidant exotic fruit on the scene is açaí palmberry, which has demonstrated in vitro prowess against various free radicals. Tests conducted at AIBMR Life Sciences, Wash., showed freeze-dried açaí powder had exceptionally high activity against superoxide and mild activity against both peroxynitrate and hydroxyl radicals.⁹² While this antioxidant potential has yet to be extensively translated to health condition research, a University of Florida, Gainesville, investigation of human leukemia cells detailed how açaí polyphenols, including anthocyanins, impacted cell proliferation and apoptosis.⁹³

Fellow exotic antioxidant fruit mangosteen—which contains xanthones as well as proanthocyanidins and catechins— has enjoyed slightly more condition-specific research, including work in brain health and cancer inhibition. In a study from Mahidol University, Thailand, mangosteen extract administered to human breast cancer cells curtailed cancer cell proliferation and ROS production, dose-dependently.⁹⁴ In subsequent Thai research, various mangosteen hull extracts exhibited antioxidant activity against hydrogen peroxide-induced oxidative stress in neuroblastoma cells, but the water and 50-percent ethanol extracts turned in the high free radical-scavenging activity, indicating they may be the most neuroprotective of the mangosteen extracts.⁹⁵

Flavonoids are considered the active compounds behind antioxidant findings in research on tea, cocoa and coffee. Epidemiologial research has hinted at an antioxidant action underlying coffee’s lifeprolonging benefits,⁹⁶ and it appears this hypothesis has some merit. A 2007 paper on coffee and DNA-stability stated subjects drinking 600 mL/d for five days had a strong reduction of DNA migration attributable to endogenous formation of oxidized purines and pyrimidines.⁹⁷ DNA damage caused by hydrogen peroxide radicals was also significantly reduced following coffee consumption, and SOD activity increased, although the treatment protocol GPx activity was only marginally affected. And in recent Spanish research, pretreatment of human hepatoma cells with coffee melanoidin conferred some protection against oxidative injury.⁹⁸

So far, however, tea wins the hotbeverage antioxidant battle, as positive research piles up on tea catechins and various major health conditions. The most popular of tea catechins, epigallocatechin gallate (EGCG), abundant in green tea, has produced some poignant results against cancer cells. Most recently, treatment of MCF-7 cancer culture-induced a poptosis, including mitochondrial changes.⁹⁹ The researchers noted low concentration of EGCG directly increased intracellular oxidative stress, while higher concentration did not. Similar research has brought black tea into the mix, as in a U.S Department of Agriculture (USDA) study involving nine green tea catechins, three black tea theaflavins and theanine, all which were tested in both cancer and normal cell lines, including MCF-7 breast cells, HT-29 colon cells, HepG2 liver cells and PC-3 prostate cells.¹⁰⁰ All extracts prompted apoptosis in all cancer lines, but the magnitude of anti-carcinogenic activity varied widely depending on tea compound concentration and the cell line culture. Researchers concluded consumers would get better anti cancer benefit from consuming both green and black teas. However, an April 2007 paper from Annamalai University, India, outlined the effect of black tea-derived polyphenon-Bonincidenceofmammary tumorsvia management of oxidant-antioxidant status, as well as modulation of enzymes that metabolize xenobiotics (foreign substances in the body).¹⁰¹

Tea is also protective in the lungs, which are susceptible to damage from cigarette smoke. Research shows exposure to cigarette smoke causes oxidative damage, inflammation, apoptosis and general lung injury, all devastations that can be limited by black tea supplementation.¹⁰² Pulmonary fibrosis, which involves free radicals and oxidative injury, can also damage the lungs.

In a Korean study, herbicide-induced fibrosis in rats was treated with green tea extract (GTE), fibrosis was significantly decreased in both partially and fully GTE-treated rats, an outcome researchers attributed partially to reduction of oxidative stress.¹⁰³

Lipid peroxidation also draws tea’s wrath. Various green tea extracts and its catechins, including EGCG, ECG and EC, were tested against oxidative modifications of LDL cholesterol.¹⁰⁴ According to results, green tea extract most effectively prevented lipid peroxidation, with only a mild inhibition credited to catechins. The researchers hypothesized green tea decreases hydroperoxide concentration and increases tryptophan.

More recently, oxide-induced lipid peroxidation in liver culture was decreased by 10 mg/ml treatment of green tea polyphenols.¹⁰⁵ Similar benefits were found with black tea extract, which ameliorated toxin-induced lipid peroxidation in mouse kidney.¹⁰⁶

Tea aside, one of the most enjoyable antioxidant remedies is chocolate, which is chock full of flavanols and other polyphenols. Scientists from Hershey Corp. investigated the antioxidant activity and polyphenol content of various forms of chocolate—natural cocoa, unsweetened baking chocolate, dark chocolate, semisweet chocolate, milke chocolate and chocolate syrup—using four testing methods: oxygen radical absorbance capacity (ORAC), vitamin C equivalence antioxidant capacity (VCEAC), total polyphenols, and procyanidins.¹⁰⁷ Natural cocoas tested highest for antioxidant activities, total polyphenols and procyanidins. Syrups were the least active. Scientists noted nonfat cocoa solid fat content of each cocoa form correlated closely with ORAC score, polyphenol count and procyanidin content.

Form aside, the bulk of health research on this delectable antioxidant focuses on endothelial and cardiovascular health. Epidemiological study has linked flavanol-rich cocoa intake and cardiac mortality, and experts speculate the benefit of cocoa might be solely in its improvements to endothelial function and protection against lipid peroxidation.¹⁰⁸

University of Scranton, Pa., food chemists detailed the effects of cocoa catechin’s ex vivo inhibition of lipid peroxidation, via binding to LDL molecules.¹⁰⁹ They noted cocoa powder and dark chocolate are the best sources of antioxidant polyphenols with less pro-oxidant saturated fat. In 2007, a German study reported daily consumption of a flavanol-rich cocoa drink for at least seven days significantly increased flow-mediated dilation in smokers with endothelial dysfunction, but did not affect various oxidative stress markers.¹¹⁰

Tea, coffee and chocolate are good examples of highly antioxidant plant foods, but other botanicals contain potent antioxidant compounds. The most studied of these antioxidant plant extracts may be French maritime pine bark extract (as Pycnogenol®, from Natural Health Science). In an animal study from Moi University, Eldoret, Kenya, supplementation with Pyc nogenol, in conjunction with a low-carbohydrate diet, inhibited oxidative damage and increased activity of the antioxidant enzymes GPx and glutathione reductase (GR) in the animals’ retinas, inhibiting diabetic retinopathy and cataract formation.¹¹¹ Additional study of diabetic rat s revealed Pycnogenol administration decreased markers of free radical damage.¹¹² And, a study from Loma Linda University, Loma Linda, Calif., showed treatment of murine macrophages with Pycnogenol inhibited oxidative burst in cells, LDL peroxidation and hydroxyl radical-induced breakage of plasmid DNA.¹¹³

Rosa Roxburghii , also known as chestnut rose, has also demonstrated antioxidant benefits in vivo, especially on LDL oxidation. A 2005 trial reported fruit from this botanical increased plasma antioxidant capacity and the ratio of glutathione-to-glutathione oxidase.¹¹⁴ The juice from this fruit significantly reduced LDL oxidative susceptibility in a murine model, in addition to suppressing macrophage growth (foam cell development) and cholesterol ester accumulation relative to oxidized LDL.¹¹⁵

By directly inhibiting oxygen free radicals or oxidative stress, or by boosting t h e concentrations and activities of existing serum and tissue antioxidant levels, m a n y supplemental antioxidants have showcased their potential benefits to chronic, degenerative health problems, including CVD, cancer, neurological decline, lung disease and eye conditions. As their mechanism become clearer and the benefits more proven, these ingredients will become even more popular and in even greater demand they currently are. 

References

1. Dragsted LO et al. "The 6-a-day study: effects of fruit and vegetables on markers of oxidative stress and antioxidative defense in healthy nonsmokers. Am J Clin Nutr. 79, 6:1060-72, 2004.www.ajcn.org

2. Taylor EW et al. “Nutrition, HIV, and drug abuse: the molecular basis of a unique role for selenium.” J Acquir Immune Defic Syndr. 25 Suppl 1:S53-61, 200.

3. Foster HD. “How HIV-1 causes AIDS: implications for prevention and treatment. Med Hypotheses. 62(4):549-53, 2004.

4. Shen X et al. “Protection of cardiac mitochondria by overexpression of MnSOD reduces diabetic cardiomyopathy.” Diabetes.55(3):798-805, 2006. http://diabetes.diabetesjournals.org/cgi/content/full/55/3/798

5. Kim GW et al. “Manganese superoxide dismutase deficiency exacerbates cerebral infarction after focal cerebral ischemia/reperfusion in mice: implications for the production and role of superoxide radicals.” Stroke. 33(3):809-15, 2002. http://stroke.ahajournals.org/cgi/content/full/33/3/809

6. Elchuri S et al. “CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life.” Oncogene. 24(3):367-80, 2005. http://www.nature.com/onc/journal/v24/n3/abs/1208207a.html

7. Didion SP et al. “Heterozygous CuZn superoxide dismutase deficiency produces a vascular phenotype with aging.” Hypertension. 48(6):1072-9, 2006. http://hyper.ahajournals.org/cgi/content/full/48/6/1072

8. Muth CM et al. “Influence of an orally effective SOD on hyperbaric oxygen-related cell damage.” Free Radic Res. 38(9):927-32, 2004.

9. Vouldoukis I et al. Phytother Res. 18, 12:957-62, 2004.6:411-22, 1989.

10. Mac-Mary S et al. “Could a photobiological test be a suitable method to assess the anti-oxidant effect of a nutritional supplement (Glisodin ®)?” Eur J Dermatol. 17, 3: 2007. http://www.europeanjournalofdermatology.com/

11. Li G et al. "Effects of Cu/Zn superoxide dismutase on strain injury-induced oxidative damage to skeletal muscle in rats. Physiol Res. 54, 2:193-9, 2005. www.biomed.cas.cz/physiolres/

12. Gomez M et al. "Pro-oxidant activity of aluminum in the rat hippocampus: gene expression of antioxidant enzymes after melatonin administration. Free Radic Biol Med. 38, 1:104-11, 2005.www.sciencedirect.com

13. Sindhu KM et al. “Melatonin protects against rotenone-induced oxidative stress in a hemiparkinsonian rat model.” J Pineal Res. 42(3):247-53, 2007. http://www.blackwell-synergy.com/doi/abs/10.1111/j.1600-079X.2006.00412.x

14. Esrefoglu M et al. "Antioxidative effect of melatonin, ascorbic acid and N-acetylcysteine on caerulein-induced pancreatitis and associated liver injury in rats. World J Gastroenterol. 12, 2:259-64, 2006.www.wjgnet.com

15. Laurin D et al. "Midlife dietary intake of antioxidants and risk of late-life incident dementia: the Honolulu-Asia Aging Study." Am J Epidemiol. 159, 10:959-67, 2004.www.aje.oupjournals.org

16. Age-Related Eye Disease Study Research Group. “A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8.” Arch Ophthalmol. 119, 10:1417-36, 2001. http://archopht.ama-assn.org

17. Erbs S et al. "Improvement of peripheral endothelial dysfunction by acute vitamin C application: different effects in patients with coronary artery disease, ischemic and dilated cardiomyopathy." Am Heart J. 146, 2:280-5, 2003. www2.us.elsevierhealth.com

18. Peake JM. "Vitamin C: effects of exercise and requirements with training." Int J Sport Nutr Exerc Metab. 13, 2:125-51, 2003. http://www.humankinetics.com/IJSNEM/journalAbout.cfm  

19. Liu JF et al. "Blood Lipid Peroxides and Muscle Damage Increased following Intensive Resistance Training of Female Weightlifters." Ann N Y Acad Sci. 1042:255-61, 2005. www.annalsnyas.org

20. Tauler P et al. "Influence of vitamin C diet supplementation on endogenous antioxidant defences during exhaustive exercise." Pflugers Arch. 446, 6:658-64, 2003.

21. Bryer SC and Goldfarb AH. “Effect of high dose vitamin C supplementation on muscle soreness, damage, function, and oxidative stress to eccentric exercise.” Int J Sport Nutr Exerc Metab. 16(3):270-80, 2006.

22. Traber MG. “Relationship of vitamin E metabolism and oxidation in exercising human subjects.” Br J Nutr. 96 Suppl 1:S34-7, 2006. http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=929160

23. You T et al. "Oxidative stress response in normal and antioxidant supplemented rats to a downhill run: changes in blood and skeletal muscles.” Can J Appl Physiol. 6:677-89, 2005.

24. Salonen RM et al. "Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression: the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study." Circulation. 107, 7:947-53, 2003. http://circ.ahajournals.org/

25. Bruno RS et al. “Faster plasma vitamin E disappearance in smokers is normalized by vitamin C supplementation.” Free Radic Biol Med. 40(4):689-97, 2006. http://dx.doi.org/10.1016/j.freeradbiomed.2005.10.051

26. Ismail NM et al. "Vitamin E and factors affecting atherosclerosis in rabbits fed a cholesterol-rich diet." Int J Food Sci Nutr. 51 Suppl:S79-94, 2000.

27. Kaikkonen J et al. "Supplementation with vitamin E but not with vitamin C lowers lipid peroxidation in vivo in mildly hypercholesterolemic men." Free Radic Res. 35, 6:967-78, 2001. http://www.tandf.co.uk/journals/titles/10715762.asp 

28. Cherubini A et al. "High vitamin E plasma levels and low low-density lipoprotein oxidation are associated with the absence of atherosclerosis in octogenarians." J Am Geriatr Soc. 49, 5:651-4, 2001.www.blackwell-synergy.com

29. Frenoux JM et al. "Very high alpha-tocopherol diet diminishes oxidative stress and hypercoagulation in hypertensive rats but not in normotensive rats. Med Sci Monit. 8, 10:BR401-7, 2002.www.medscimonit.com

30. Costacou T et al. “Antioxidants and coronary artery disease among individuals with type 1 diabetes: Findings from the Pittsburgh Epidemiology of Diabetes Complications Study.” J Diabetes Complications. 20(6):387-94, 2006. http://dx.doi.org/10.1016/j.jdiacomp.2005.10.007

31. Khanna S et al. “Characterization of the potent neuroprotective properties of the natural vitamin E alpha-tocotrienol.” J Neurochem. 98(5):1474-86, 2006. http://www.blackwell-synergy.com/doi/abs/10.1111/j.1471-4159.2006.04000.x

32. Khosla P et al. “Postprandial levels of the natural vitamin E tocotrienol in human circulation.” Antioxid Redox Signal. 8(5-6):1059-68, 2006. http://www.liebertonline.com/doi/abs/10.1089/ars.2006.8.1059

33. Morris MC et al. “Vitamin E and cognitive decline in older persons.” Archives of Neurology. 59:1125-32, 2002. http://archneur.ama-assn.org

34. Itoh H et al. "Vitamin E supplementation attenuates leakage of enzymes following 6 successive days of running training." Int J Sports Med. 21, 5:369-74, 2000. http://www.thieme.de/fz/sportsmed/

35. Naguib Y et al. "Antioxidant activities of natural vitamin E formulations." J Nutr Sci Vitaminol (Tokyo). 29, 4:217-20, 2003. http://eishoku.bcasj.or.jp/journal-e.html 

36. Galli F et al. "The effect of alpha- and gamma-tocopherol and their carboxyethyl hydroxychroman metabolites on prostate cancer cell proliferation. Arch Biochem Biophys. 423, 1:97-102, 2004.www.elsevier.com

37. Conklin KA et al. Coenzyme q10 for prevention of anthracycline-induced cardiotoxicity. Integr Cancer Ther. 4, 2:110-30, 2005. http://www.sagepub.com/journal.aspx?pid=286

38. Lakomkin VL et al. "Changes in antioxidant status of myocardium during oxidative stress under the influence of coenzyme Q10. Biochemistry (Mosc). 70, 1:79-84, 2005.

39. Singh RB et al. "Effect of coenzyme Q10 on experimental atherosclerosis and chemical composition and quality of atheroma in rabbits." Atherosclerosis. 148, 2:275-82, 2000.www.elsevier.com

40. Chapidze G et al. "Prevention of coronary atherosclerosis by the use of combination therapy with antioxidant coenzyme Q10 and statins. Georgian Med News. 118:20-5, 2005.

41. Lakomkin VL et al. "Changes in antioxidant status of myocardium during oxidative stress under the influence of coenzyme Q10. Biochemistry (Mosc). 70, 1:79-84, 2005.

42. Thirunavukkarasu V et al. "Cardiac lipids and antioxidant status in high fructose rats and the effect of alpha-lipoic acid. Nutr Metab Cardiovasc Dis. 2004 14, 6:351-7.www.sciencedirect.com

43. Ku an S et al. "L-carnitine and DL-alpha-lipoic acid reverse the age-related deficit in glutathione redox state in skeletal muscle and heart tissues. Mech Ageing Dev. 125, 7:507-12, 2004.

44. Cheng TJ et al. “Protection against arsenic trioxide-induced autophagic cell death in U118 human glioma cells by use of lipoic acid.” Food Chem Toxicol. 45(6):1027-38, 2007. http://dx.doi.org/10.1016/j.fct.2006.12.014

45. Jia L et al. “Acrolein, a toxicant in cigarette smoke, causes oxidative damage and mitochondrial dysfunction in RPE cells: protection by (R)-alpha-lipoic acid.” Invest Ophthalmol Vis Sci. 48, 1:339-48, 2007. http://www.iovs.org/cgi/content/abstract/48/1/339

46. Santos JM et al. “Protective effect of alpha-lipoic acid in experimental spermatic cord torsion.” Nutrition. 23(1):76-80, 2007. http://dx.doi.org/10.1016/j.nut.2006.09.005

47. Wan XS et al. "Protection against radiation-induced oxidative stress in cultured human epithelial cells by treatment with antioxidant agents. Int J Radiat Oncol Biol Phys. 64, 5:1475-81, 2006.

48. Keck AS et al. "Aqueous extracts of selenium-fertilized broccoli increase selenoprotein activity and inhibit DNA single-strand breaks, but decrease the activity of quinone reductase in Hepa 1c1c7 cells. Food Chem Toxicol. 44, 5:695-703, 2006. www.sciencedirect.com

49. Lu J et al. "Selenium and cancer chemoprevention: hypotheses integrating the actions of selenoproteins and selenium metabolites in epithelial and non-epithelial target cells.Antioxid Redox Signal. 7, (11-12):1715-27, 2005.

50. Danesi F et al. "Counteraction of adriamycin-induced oxidative damage in rat heart by selenium dietary supplementation. J Agric Food Chem. 54, 4:1203-8, 2006. http://pubs.acs.org/journals/jafcau/index.html

51. Dani V et al. "Radioprotective role of zinc following single dose radioiodine (131I) exposure to red blood cells of rats." Indian J Med Res. 122, 4:338-42, 2005.

52. Aydin A et al. "Oxidative stress and antioxidant status in non-metastatic prostate cancer and benign prostatic hyperplasia. Clin Biochem. 39, 2:176-9, 2006.

53. van leeuwen R et al. “Dietary intake of antioxidants and risk of age-related macular degeneration.” JAMA. 294(24):3101-7, 2005. http://jama.ama-assn.org/cgi/content/short/294/24/3101

54. Tuzcu M and Baydas G. “Effect of melatonin and vitamin E on diabetes-induced learning and memory impairment in rats.” Eur J Pharmacol. 537(1-3):106-10, 2006. http://dx.doi.org/10.1016/j.ejphar.2006.03.024

55. Marsh SA et al. “Effects of antioxidant supplementation and exercise training on erythrocyte antioxidant enzymes.” Int J Vitam Nutr Res. 76(5):324-31, 2006.

56. Nikolova D et al. “Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis.” JAMA. 297, 8:842-57, 2007. http://jama.ama-assn.org/cgi/content/short/297/8/842

57. Heinrich U et al. “Antioxidant supplements improve parameters related to skin structure in humans.” Skin Pharmacol Physiol. 19(4):224-3, 2006.

58. Sanz MM et al. “Significant photoreceptor rescue by treatment with a combination of antioxidants in an animal model for retinal degeneration.” Neuroscience. 145(3):1120-9, 2007. http://dx.doi.org/10.1016/j.neuroscience.2006.12.034

59. Jiang J et al. "Plasma carotenoid, alpha-tocopherol and retinol concentrations and risk of colorectal adenomas: A case-control study in Japan. Cancer Lett. 226, 2:133-41, 2005.www.sciencedirect.com

60. Krinsky NI et al. "Carotenoid actions and their relation to health and disease. Mol Aspects Med." 26, 6:459-516, 2005.www.sciencedirect.com

61. Reddy L et al. "Aflatoxin B1-induced toxicity in HepG2 cells inhibited by carotenoids: morphology, apoptosis and DNA damage." Biol Chem. 387, 1:87-93, 2006. www.degruyter.com

62. Kaliora AC et al. "Dietary antioxidants in preventing atherogenesis. Atherosclerosis. Nov 25, 2005 [Epub before print].www.elsevier.com

63. Engelhard YN et al. "Natural antioxidants from tomato extract reduce blood pressure in patients with grade-1 hypertension: a double-blind, placebo-controlled pilot study. Am Heart J. 151, 1:100, 2006.www.elsevier.com

64. Porrini M et al. "Daily intake of a formulated tomato drink affects carotenoid plasma and lymphocyte concentrations and improves cellular antioxidant protection." Br J Nutr. 93, 1:93-9, 2005.www.ingentaconnect.com

65. Presented by Yossi Levy, Ph.D., professor of clinical biochemistry at Ben Gurion University, Beer Sheva, Israel, at the Cosmeceutical Summit in Fort Lauderdale, Fla. http://www.naturalproductsinsider.com/articles/07apr09studies7.html

66. Presented by Yossi Levy, Ph.D., professor of clinical biochemistry at Ben Gurion University, Beer Sheva, Israel, at the Cosmeceutical Summit in Fort Lauderdale, Fla. http://www.naturalproductsinsider.com/articles/07apr09studies7.html

67. Krinsky NI et al. "Carotenoid actions and their relation to health and disease. Mol Aspects Med. 26, 6:459-516, 2005.www.sciencedirect.com

68. Richer S et al. “Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial).” Optometry. 75, 4:216-30, 2004.

69. Koh HH. "Plasma and macular responses to lutein supplement in subjects with and without age-related maculopathy: a pilot study. Exp Eye Res. 79, 1:21-7, 2004. www.sciencedirect.com

70. Chitchumroonchokchai C et al. “Xanthophylls and alpha-tocopherol decrease UVB-induced lipid peroxidation and stress signaling in human lens epithelial cells.” J Nutr. 134, 12:3225-32, 2004. http://jn.nutrition.org/cgi/content/full/134/12/3225

71. Santocono M et al. “Influence of astaxanthin, zeaxanthin and lutein on DNA damage and repair in UVA-irradiated cells.” J Photochem Photobiol B. 85(3):205-15, 2006. http://dx.doi.org/10.1016/j.jphotobiol.2006.07.009

72. Kappagoda CT et al. Presented at SupplySide West, November 2006. http://www.naturalproductsinsider.com/articles/472/6bh14920968056.html

73. Puiggros F et al. “Grape seed procyanidins prevent oxidative injury by modulating the expression of antioxidant enzyme systems.” J Agric Food Chem. 53(15):6080-6, 2005. http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2005/53/i15/abs/jf050343m.html

74. Montilla P et al. “Protective effect of red wine on oxidative stress and antioxidant enzyme activities in the brain and kidney induced by feeding high cholesterol in rats.” Clin Nutr. 25(1):146-53, 2006. http://dx.doi.org/10.1016/j.clnu.2005.10.004

75. Balu M et al. “Age-related oxidative protein damages in central nervous system of rats: modulatory role of grape seed extract.” Int J Dev Neurosci. 23(6):501-7, 2005. http://dx.doi.org/10.1016/j.ijdevneu.2005.06.001

76. Balu M et al. “Modulatory role of grape seed extract on age-related oxidative DNA damage in central nervous system of rats.” Brain Res Bull. 68(6):469-73, 2006.

77. Talavera S et al. “Anthocyanins Are Efficiently Absorbed from the Stomach in Anesthetized Rats.” J Nutr. 133:4178-4182, 2003. http://jn.nutrition.org/cgi/content/abstract/133/12/4178

78. Talavera S et al. “Anthocyanins Are Efficiently Absorbed from the Small Intestine in Rats.” J Nutr. 134:2275-2279, 2004. http://jn.nutrition.org/cgi/content/abstract/134/9/2275

79. Talavera S et al. “Bioavailability of a bilberry anthocyanin extract and its impact on plasma antioxidant capacity in rats.” J Sci Food Agr. 86, 1:96-7, 2005. http://www3.interscience.wiley.com/cgi-bin/abstract/111083121/ABSTRACT

80. Milbury, P.E et al. “Anthocyanins cross the blood brain barrier: effects on oxidative stress-induced apop-tosis” Paper presented at: 229th ACS National Meeting,AGFD-171, San Diego, Calif., 2005.

81. Reed JD. “Cranberry flavonoids, atherosclerosis and cardiovascular health.” Crit Rev Food Sci Nutr. 42(3 Suppl):301-16, 2002.

82. Youdim KA et al. “Polyphenolics enhance red blood cell resistance to oxidative stress: in vitro and in vivo.” Biochim Biophys Acta. 1523(1):117-22, 2000. http://dx.doi.org/10.1016/S0304-4165(00)00109-4

83. Bagchi D et al. Anti-angiogenic, antioxidant, and anti-carcinogenic properties of a novel anthocyanin-rich berry extract formula. Biochemistry (Mosc). 69, 1:75-80, 2004. http://www.protein.bio.msu.su/biokhimiya

84. Bagchi D et al. "Safety and Whole-Body Antioxidant Potential of a Novel Anthocyanin-Rich Formulation of Edible Berries." Molecular and Cellular Biochemistry 281:197-209, 2005.

85. Abidov M et al. “Efficiency of pharmacologically-active antioxidant phytomedicine Radical Fruits in treatment hypercholesteremia at men.” Georgian Med News. 140:78-83, 2006.

86. de Nigris F et al. “Effects of a pomegranate fruit extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis.” Cardiovasc Res. 73(2):414-23, 2007. http://dx.doi.org/10.1016/j.cardiores.2006.08.021

87. Ignarro LJ et al. “Pomegranate juice protects nitric oxide against oxidative destruction and enhances the biological actions of nitric oxide.” Nitric Oxide. 15(2):93-102, 2006. http://dx.doi.org/10.1016/j.niox.2006.03.001

88. Hartman RE et al. “Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease.” Neurobiol Dis. 24(3):506-15, 2006. http://dx.doi.org/10.1016/j.nbd.2006.08.006

89. Guo S et al. “Evaluation of antioxidant activity and preventing DNA damage effect of pomegranate extracts by chemiluminescence method.” J Agric Food Chem. 55(8):3134-40, 2007. http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2007/55/i08/abs/jf063443g.html

90. Rosenblat M et al. "Pomegranate byproduct administration to apolipoprotein e-deficient mice attenuates atherosclerosis development as a result of decreased macrophage oxidative stress and reduced cellular uptake of oxidized low-density lipoprotein." J Agric Food Chem. 54, 5:1928-35, 2006. http://pubs.acs.org/journals/jafcau/index.html

91. de Nigris F et al. “Effects of a pomegranate fruit extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis.” Cardiovasc Res. 73(2):414-23, 2007. http://dx.doi.org/10.1016/j.cardiores.2006.08.021

92. Schauss AG et al. “Antioxidant capacity and other bioactivities of the freeze-dried Amazonian palm berry, Euterpe oleraceae mart. (acai).” J Agric Food Chem. 54(22):8604-10, 2006. http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2006/54/i22/abs/jf0609779.html

93. Percival SS et al. “Acai (Euterpe oleracea Mart.) polyphenolics in their glycoside and aglycone forms induce apoptosis of HL-60 leukemia cells.” J Agric Food Chem. 22;54(4):1222-9, 2006. http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2006/54/i04/abs/jf052132n.html

94. Moongkarndi P et al. “Antiproliferation, antioxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line.” J Ethnopharmacol. 90(1):161-6, 2004. http://dx.doi.org/10.1016/j.jep.2003.09.048

95. Weecharangsan W et al. “Antioxidative and neuroprotective activities of extracts from the fruit hull of mangosteen (Garcinia mangostana Linn.).” Med Princ Pract. 15(4):281-7, 2006. http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=MPP2006015004281

96. Andersen MF et al. “Consumption of coffee is associated with reduced risk of death attributed to inflammatory and cardiovascular diseases in the Iowa Women's Health Study.” Am J Clin Nutr. 83, 5:1039-46, 2006. http://www.ajcn.org/cgi/content/full/83/5/1039

97. Bichler J et al. “Coffee consumption protects human lymphocytes against oxidative and 3-amino-1-methyl-5H-pyrido[4,3-b]indole acetate (Trp-P-2) induced DNA-damage: Results of an experimental study with human volunteers.” Food Chem Toxicol. Epub online ahead of print, 2007 Feb 12. http://dx.doi.org/10.1016/j.fct.2007.02.001

98. Goya L et al. “Effect of coffee Melanoidin on human hepatoma HepG2 cells. Protection against oxidative stress induced by tert-butylhydroperoxide.” Mol Nutr Food Res. 51(5):536-45, 2007. http://www3.interscience.wiley.com/cgi-bin/abstract/114209240/ABSTRACT

99. Hssuw YD and Chan WH. “Epigallocatechin gallate dose-dependently induces apoptosis or necrosis in human MCF-7 cells.” Ann N Y Acad Sci.1095:428-40, 2007. http://www.annalsnyas.org/cgi/content/full/1095/1/428

100. Friedman M et al. “Structure-activity relationships of tea compounds against human cancer cells.” J Agric Food Chem.55(2):243-53, 2007. http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2007/55/i02/abs/jf062276h.html

101. Kumaraguruparan R et al. “Chemoprevention of rat mammary carcinogenesis by black tea polyphenols: Modulation of xenobiotic-metabolizing enzymes, oxidative stress, cell proliferation, apoptosis, and angiogenesis.” Mol Carcinog. Epub online ahead of print: 2007 Apr 5. http://www3.interscience.wiley.com/cgi-bin/abstract/114207234

102. Banerjee S et al. “Black tea prevents cigarette smoke-induced apoptosis and lung damage.” J Inflamm (Lond). 4:3, 2007. http://www.journal-inflammation.com/content/4/1/3

103. Kim HR et al. “Green tea extract inhibits paraquat-induced pulmonary fibrosis by suppression of oxidative stress and endothelin-l expression.” Lung. 184(5):287-95, 2006. http://www.springerlink.com/content/0046l10n18078r06/

104. Ostrowska J and Skrzydlewska E. “The comparison of effect of catechins and green tea extract on oxidative modification of LDL in vitro.” Adv Med Sci. 51:298-303, 2006.

105. Srinivasan P et al. “Attenuation of 4-nitroquinoline 1-oxide induced in vitro lipid peroxidation by green tea polyphenols.” Life Sci. 80(12):1080-6, 2007. http://dx.doi.org/10.1016/j.lfs.2006.11.051

106. Choudhary A and Verma RJ. “Black tea ameliorates aflatoxin-induced lipid peroxidation in the kidney of mice.” Acta Pol Pharm. 63(4):307-10, 2006.

107. Miler KB et al. “Antioxidant activity and polyphenol and procyanidin contents of selected commercially available cocoa-containing and chocolate products in the United States.” J Agric Food Chem. 54(11):4062-8, 2006. http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2006/54/i11/abs/jf060290o.html

108. Steffen et al. “Myeloperoxidase-mediated LDL oxidation and endothelial cell toxicity of oxidized LDL: attenuation by (-)-epicatechin.” Free Radic Res. 40(10):1076-85, 2006. http://www.informaworld.com/smpp/content?content=10.1080/10715760600883247

109. Vinson JA et al. “Chocolate is a powerful ex vivo and in vivo antioxidant, an antiatherosclerotic agent in an animal model, and a significant contributor to antioxidants in the European and American Diets.” J Agric Food Chem. 54(21):8071-6, 2006. http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2006/54/i21/abs/jf062175j.html

110. Heiss C et al. “Sustained increase in flow-mediated dilation after daily intake of high-flavanol cocoa drink over 1 week.” J Cardiovasc Pharmacol. 49(2):74-80, 2007. http://www.cardiovascularpharm.com/pt/re/jcardiopharm/abstract.00005344-200702000-00002.htm

111. Kamuren ZT et al. "Effects of low-carbohydrate diet and Pycnogenol treatment on retinal antioxidant enzymes in normal and diabetic rats. J Ocul Pharmacol Ther. 22, 1:10-8, 2006.

112. Berryman AM et al. "Influence of treatment of diabetic rats with combinations of pycnogenol, beta-carotene, and alpha-lipoic acid on parameters of oxidative stress." J Biochem Mol Toxicol. 18, 6:345-52, 2004.

113. Nelson AB et al. "Pycnogenol inhibits macrophage oxidative burst, lipoprotein oxidation, and hydroxyl radical-induced DNA damage." Drug Dev Ind Pharm. 24, 2:139-44, 1998.

114. Erasmus E et al. “Rosa roxburghii supplementation in a controlled feeding study increases plasma antioxidant capacity and glutathione redox state.” Eur J Nutr. 44(7):452-7, 2005. http://www.springerlink.com/content/q0445x6386t83152/

115. Zhang C et al. “Inhibitory effects of rosa roxburghii tratt juice on in vitro oxidative modification of low density lipoprotein and on the macrophage growth and cellular cholesteryl ester accumulation induced by oxidized low density lipoprotein.” Clin Chim Acta. 313(1-2):37-43, 2001. http://dx.doi.org/10.1016/S0009-8981(01)00647-7

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