Antioxidant Defense

Antioxidant Defense
by Heather Granato

It is one of the great ironies of life that the critical molecule oxygen, which keeps us alive, also is inherently responsible for setting into motion processes that contribute to the aging process and degradation of the body. However, Mother Nature did build in protective mechanisms in the form of endogenous and exogenous antioxidants—substances that fight the oxidative cascade and protect the body from the cellular level up.

Since Denham Harman, M.D., Ph.D., first proposed the “free radical” theory of aging in the 1950s, nutritionists have sought to understand the body’s oxidation process and how to prevent damage caused by rogue oxygen molecules. There is growing evidence that the production of reactive oxygen species (ROS), including free radicals, is behind the aging process and initiation of age-related disease.

Oxidative stress is induced by a wide range of environmental factors and simple metabolism. For example, the immune system produces ROS in response to infection or damage by external factors like environmental toxins. These free radicals have an unpaired electron, a situation the free radical remedies by stealing an electron from a stable molecule. This sets off a chain reaction that can damage the body’s proteins and cell membranes, weaken the cells’ natural defenses and disrupt cells’ DNA. Accumulated damage can lead to widespread biomolecular changes, leaving the body susceptible to degenerative disease conditions.

To fight the damage, nature developed antioxidants, substances that quench free radicals by donating electrons to molecules before they damage other cells. Studies have indicated certain antioxidants may have additional activities, such as reducing the energy of a free radical or stopping it from forming by interrupting an oxidizing chain reaction. Antioxidants may also trap free radicals and lipid peroxides, delaying the onset of lipid peroxidation, stalling production of further free radicals and inhibiting the damaging effects of certain enzymes that can degrade connective tissues.

Antioxidants can be endogenous (produced by the body) or exogenous (obtained through the diet). Endogenous antioxidants include enzymes, coenzymes and sulfur-containing compounds such as glutathione. Exogenous antioxidants include vitamins C and E, bioflavonoids and carotenes. In fact, the term “antioxidant” is applied to dozens of different kinds of nutrients, botanicals and supplements, from grape seed extract and selenium to alpha-lipoic acid and superoxide dismutase.

Researchers have investigated the role of antioxidants to work in a number of systems. A review from the University of Sao Paulo, Brazil, noted the ability of nutraceutical antioxidants to work at a molecular level, stabilizing mitochondrial function and quenching free radical activity, may hold the key to their ability to prevent agingrelated chronic diseases.¹ In addition, a study in vegetarians that found reduced endogenous DNA damage and higher antioxidant status suggests increased intake of compounds such as vitamin C, vitamin E and beta-carotene may prevent DNA strand breaks and oxidative damage.² Researchers from Slovak Technical University, Bratislava, added oxygen free radicals could be considered an important class of carcinogens, making antioxidants a key player in prevention of carcinogenesis.³

Antioxidants also play an important role in the health of the cardiovascular system. Norwegian reviewers noted antioxidants may work together to improve endogenous antioxidant defense by inducing phase II enzyme activity.⁴ Additional researchers have suggested antioxidant interventions may reduce clinical parameters of heart failure induced by oxidative stress⁵ and also prevent superoxide production associated with hypertension, particularly in models of Type IIdiabetes.⁶ The connection between oxidative stress and development of vascular complications in people with hyperglycemia suggests the ability of antioxidants to prevent complications associated with Type II diabetes.⁷ Further work has suggested the ability of antioxidants to reduce age-related cognitive impairment⁸ and age-related macular degeneration (AMD).⁹ They may even play a role in sports nutrition, helping athletes overcome oxidative damage associated with increased physical stress.¹⁰

Population studies suggest adults with higher intakes of fruits and vegetables—and therefore greater intakes of their phytonutrients—have increased antioxidant defenses. A 15-year study in more than 6,000 adults conducted at Johns Hopkins, Baltimore, found participants in the highest quintile of fruit and vegetable intake had significantly lower rates of all-cause, cancer and cardiovascular disease death.¹¹ However, intervention studies with a broad range of antioxidant substances have been less conclusive. A five-week study in 60 elderly subjects in Salt Lake City found moderate antioxidant supplementation and a diet high in carotenoids both elevated antioxidant levels, though markers of oxidative stress were not significantly different than baseline.¹²

Similarly, a four-week study in 16 healthy adults (ages 31 to 48) in Buenos Aires, Argentina, found a supplement of 106 IU vitamin E, 10 mg beta-carotene, 60 mg coenzyme Q10 (CoQ10) and 40 mcg selenium decreased plasma levels of oxidative stress and increased levels of antioxidants.¹³ Interestingly, men’s levels of oxidative stress were higher at baseline, though there was no difference between groups postintervention, leading the researchers to suggest men should optimize antioxidant intake earlier in life than women.

Researchers have also focused on specific health conditions associated with oxidative damage. A three-month antioxidant supplementation trial was conducted by researchers at the Institute of Preventive and Clinical Medicine in Bratislava, Slovak Republic, in a group of 28 heart attack survivors and 57 controls.¹⁴ The supplement contained 100 mg/d vitamin C, 100 mg/d vitamin E, 6 mg/d of beta-carotene and 50 mcg/d selenium. At the end of the trial, supplementation was associated with a decrease in the percentage of cells with chromosome aberrations, suggesting antioxidants could decrease genetic damage. Additionally, the researchers found supplementation reduced the levels of lipid peroxidation in plasma, with a more pronounced effect in the heart attack group.¹⁵ Russian researchers reported similar results, with a complex of C, E, beta-carotene and selenium reducing both primary and secondary byproducts of free radical oxidation in low-density lipoprotein (LDL) isolated from the plasma of patients with coronary heart disease.¹⁶

Combination therapy has also been used in prevention of AMD, most prominently in the Veterans LAST Study.¹⁷ Ninety patients with atrophic AMD received either 10 mg/d purified lutein (as FloraGLO® Lutein from Kemin Health), lutein plus a broad spectrum antioxidant vitamin/mineral formula, or a placebo for one year. Supplementation with both lutein and the combination formula improved visual function and increased the density of the macular pigment, which protects the eye from UV-induced oxidative damage. Combinations of antioxidants also appear to benefit neurological function, as seen in the Cache County Study, in which elderly adults who used vitamin E and multivitamins containing vitamin C had a reduced prevalence and incidence of Alzheimer’s disease.¹⁸ Similarly, Indian researchers reported a combination of antioxidants reduced parameters of oxidative stress in the brains of animals subjected to stress.¹⁹

Vitamins & Minerals

One of the most popular combinations of antioxidants is vitamin E, which is lipid soluble, with vitamin C, which is water soluble. A study in rats found a combination of ascorbate and alpha-tocopherol selectively altered the extent of arsenic-induced DNA damage by reducing TNF-alpha levels and inhibiting activation of the caspase cascade.²⁰ Similarly, a study in pregnant, diabetic rats found the combination of vitamins E and C, plus exercise, reduced lipid peroxidation and protected both the lens and kidney, which are vulnerable to free radical production.²¹ A human study also reported supplementation with vitamins C and E decreased oxidative stress and lipid peroxidation, improving renal function in transplant patients.²²

On its own, vitamin C is well known as an antioxidant. A review from the National Institutes of Health (NIH) noted vitamin C’s function as an electron donor accounts for all of its known functions, making it a potent water-soluble antioxidant for humans.²³ Researchers further noted while intervention studies with vitamin C have been inconclusive on its benefits, there appears to be an issue with determining optimal dosing levels, as well as selecting targeted patient groups known to have increased oxidative damage.

Further, Japanese reviewers noted vitamin C concentration is one of the most sensitive indices in animal tissues for oxidative stress, and links have been found between levels of oxidized LDL and plasma vitamin C levels.²⁴ And Polish researchers report vitamin C acts not only as an antioxidant in protecting DNA from oxidative damage, but may also regulate expression of genes participating in the DNA repair process.²⁵

Researchers from the University of Copenhagen, Denmark, investigated the ability of 250 mg/d vitamin C (as plain or slow release) to protect DNA from oxidative damage in male smokers.²⁶ Both formulations decreased DNA damage measured by the comet assay and DNA repair, though the slow release formula had a more pronounced and sustained protective effect on base damage compared to the plain formula. A study in male rats, conducted in India, also focused on vitamin C’s ability to protect against DNA damage in a model of lead-induced hypertension.²⁷ Lead exposure significantly increased lipid peroxidation and oxidative damage to DNA and decreased antioxidant power, while concomitant administration of vitamin C abrogated lipid peroxidation and completely prevented oxidative DNA damage.

Further studies have focused on vitamin C’s ability to protect the body from lipid peroxidation. In one trial, researchers from the University of Western Australia, Perth, administered 500 mg/d vitamin C with or without 1,000 mg/d polyphenols (grape seed extract).²⁸ Supplementation with vitamin C significantly increased plasma vitamin C levels and reduced in vivo lipid peroxidation. Similarly, German researchers who administered increasing daily doses of vitamin C from 30 mg to 2,500 mg found supplementation dosedependently increased plasma ascorbate concentrations and the resistance of plasma to lipid peroxidation.²⁹

In the lipid area, vitamin E has also been the subject of individual research. A review from the German Institute of Human Nutrition, Potsdam-Rehbrucke, noted vitamin E has significant biological activity including scavenging free radicals, regulating gene expression and modulating cell signaling pathways.³⁰ A study conducted by Soft Gel Technologies in Los Angeles examined the antioxidant activities of different natural vitamin E formulations, and found d-alpha-tocopherol, mixed tocopherols and tocotrienols all possessed powerful antioxidant effects, with the mixtures often superior to isolated alphatocopherol.³¹

In vitro work shows vitamin E (as alphatocopherol) protects against lipid peroxidation and oxidative DNA damage, as well as ionizing radiation.³² In humans, vitamin E appears necessary to improve immune function and the body’s free radical scavenging abilities. A study at Hannam University in Daejeon, Korea, investigated the antioxidant and immune effects of 400 IU/d dl-alpha-tocopherol supplementation in young, middle-aged and elderly women.³³ Vitamin E supplementation significantly increased radical scavenger activity of red blood cells, though there was no clear indication that supplementation improved humoral immune response.

While alpha-tocopherol has been the primary supplemental form of vitamin E used in most research, tocotrienols are increasingly the subject of investigation. German researchers noted tocotrienols have unique biological effects and may suppress ROS production more efficiently than tocopherols.³⁴ A comparative study of tocotrienols and tocopherols conducted at the National Institute of Advanced Industrial Science and Technology in Osaka, Japan, found both forms exerted the same antioxidant activities against lipid peroxidation and similar membrane mobilities.³⁵

Studies on palm oil mixed tocotrienols have shown beneficial effects. A study conducted at Universiti Kebangsaan Malaysia compared the efficacy of palm oil tocotrienols and pure alpha-tocopherol, and found the palm tocotrienols were more potent than alpha-tocopherol at protecting the bones of rats against free radical-induced elevation of cytokines.³⁶ Further studies have shown the ability of alpha-tocotrienol to prevent ROS-induced neuronal death³⁷ and to reduce endothelial expression of adhesion molecules.³⁸ Interesting results were posted from a study in the Ivory Coast, which compared the antioxidant capacity of subjects in a selenium deficient region consuming a vegetarian diet rich in crude palm oil with the capacity of subjects in a coastal region consuming a fish-based diet with refined palm oil.³⁹ While the subjects in the selenium deficient region had a higher exposure risk to oxidative stress, there was no apparently oxidative damage, which the researchers suggested was related to the crude palm oil’s supplying full spectrum vitamin E.

A newer supplemental form of vitamin E is vitamin E phosphate (Ester-E®, developed by Zila Nutraceuticals). While alpha-tocopherol is an active form of vitamin E, the monophosphate ester of alpha-tocopherol is a water-soluble form of vitamin E that may be converted by the body as needed into alphatocopherol.⁴⁰ Swiss researchers investigated the effect of a mixture of alpha-tocopheryl phosphate and di-alpha-tocopheryl phosphate (as Ester-E) on two cell lines, rat aortic smooth muscle cells and human monocytic leukemia cells.⁴¹ The compound inhibited cell proliferation in both lines, and curtailed oxidized LDL surface binding and uptake, inhibiting the major elements involved in the progression of atherosclerosis. In addition, Dutch researchers compared the ability of several vitamin E isomers to inhibit LDL oxidation, and found vitamin E phosphate (as Ester-E) was a potent antioxidant without conversion to vitamin E by esterases, and it reduced membrane fluidity, inhibiting the transfer of free radicals between cells.⁴²

A number of studies have also examined the interaction between vitamin E and selenium. A study at Firat University, Turkey, investigated the impact of selenium with high dose vitamin E on lipid peroxidation and scavenging enzyme activity in rats subjected to cisplatin-induced toxicity.⁴³ The animals given only cisplatin showed increased lipid peroxidation in the kidney, liver and lens, and decreased antioxidant activity; however, selenium (1.5 mg/kg body weight) and vitamin E (1,000 mg/kg body weight) significantly improved antioxidant concentrations and activity and protected against peroxidative damage. Another animal study, conducted in Egypt, found pretreatment with selenium and/or vitamin E before irradiation induced free-radical scavenging systems and protected against oxidative injury.⁴⁴

On its own, selenium is a critical component of the amino acids selenocysteine and selenomethionine, which have powerful redox activity in the body.⁴⁵ In the brain, selenium appears to inhibit production of the free radical generator nitric oxide,⁴⁶ as well as prevent neurotoxicity by mediating free radical formation and oxidative stress.⁴⁷

There are additional vitamin-like compounds that also work as antioxidants in the body. As previously mentioned, CoQ10 is often used in antioxidant formulas. In its reduced form, ubiquinol, it decreases lipid peroxidation by acting as a chain-breaking antioxidant and recycling vitamin E, and it reacts with other ROS.⁴⁸ Further, CoQ10 works at the mitochondrial level, preventing oxidative damage within the cell’s power organelle.⁴⁹

A study at the University of Southern California, Los Angeles, examined the body’s response to coenzyme Q in aging.⁵⁰ Rats fed a reduced calorie diet showed depleted levels of both alpha-tocopherol and coenzyme Q in the mitochondria, leading researchers to suggest the age-related increase in mitochondrial oxidative damage may be associated with depleted levels of coenzyme Q and alpha-tocopherol in the elderly. Another animal study, conducted at the University of North Texas Health Science Center, Fort Worth, examined CoQ10 supplementation’s influence on CoQ10 content in the mitochondria and its impact on oxidative stress.⁵¹ Administration of CoQ10 increased plasma and mitochondrial levels of CoQ10, decreased protein oxidative damage and increased antioxidative potential.

CoQ10 has also been studied in conjunction with other antioxidants. A study at the University of Rome La Sapienza found administering a combination antioxidant formula (CoQ10, alphatocopherol, alpha-lipoic acid, carnitine and selenomethionine) to 20 healthy individuals significantly increased plasma antioxidant status and decreased both blood peroxide levels and generation of ROS at the mitochondrial level.⁵² Another study combining CoQ10 and aloe vera in rats with colitis found pre-treatment with the antioxidant formula inhibited ROS production in the gut and improved oxidative stress parameters.⁵³ And a study combining CoQ10 with alpha-lipoic acid, with or without calorie restriction, found the supplementation reduced oxidative stress in the heart, though not to the same degree as calorie restriction.⁵⁴

Alpha-lipoic acid on its own is another powerful antioxidant. A review from the University of Helsinki, Finland, noted alpha-lipoic acid and dihydrolipoic acid both have direct free radical scavenging properties, decreasing oxidative stress and also working to recycle levels of other antioxidants, such as vitamin E.⁵⁵ Researchers from Oregon State University, Corvallis, noted as an antioxidant, alphalipoic acid directly terminates free radicals, chelates transition metal ions and augments endogenous antioxidant activity.⁵⁶

This antioxidant activity translates to powerful protection against disease states including cardiovascular disease, as it protects against LDL oxidation and modulates hypertension.⁵⁷ A study at the State University of Ceara, Brazil, found alpha-lipoic acid given to rabbits prior to administration of an endothelium agonist improved the aortic response to the endothelium.⁵⁸ And Mexican researchers found alpha-lipoic acid was able to reduce cerebral damage levels by protecting against lipid peroxidation prior to induction of stroke in rats.⁵⁹ Further, Indian researchers found alpha-lipoic acid was able to prevent arsenic-induced oxidative damage in rat brains, which the researchers attributed to its combination of free radical scavenging and metal chelating properties.⁶⁰

Carotenoids

Beyond the vitamins and minerals, there are a host of additional antioxidant nutrients. One of the leading categories is the carotenoids. These natural, fat-soluble pigments occur widely in the natural kingdom—from plants and bacteria to fungi and animals. The first carotenoid was discovered in the early 1830s, when a scientist isolated carotene from carrots. Today, there are more than 700 known natural carotenoids; as many as 50 may be absorbed and metabolized by the human body. To date, however, only 14 have been identified in human serum.

Carotenoids have a distinctive pattern of alternating single and double bonds in a polyene backbone. The chain may be terminated by cyclic end-groups (rings) and may be complemented with oxygencontaining functional groups.The hydrocarbon carotenoids are known as carotenes, and those with oxygenated derivatives of these hydrocarbons are xanthophylls.

Carotenoids are excellent scavengers of singlet oxygen and also work to scavenge other types of ROS.⁶¹ They also appear to induce the activity of phase II detoxification enzymes⁶² and work to protect neutrophils from becoming autotoxic after releasing ROS in response to pathogenic challenges.⁶³ In addition, the carotenoids work to enhance cell-mediated and humoral immune response; this ability, together with their activity against ROS, makes them potentially useful in preventing pathologies such as cancer, cardiovascular disease and neurodegeneration.⁶⁴

Many research studies have used plasma levels of carotenoids as markers for fruit and vegetable intake. A nested, case-control analysis conducted by the Harvard School of Public Health, Boston, compared levels of major carotenoids in 297 physicians with ischemic stroke and paired controls.⁶⁵ Baseline plasma levels of alpha-carotene, betacarotene and lycopene were inversely related to risk of ischemic stroke, with a tendency toward inverse association found for betacryptoxanthin. Another nested, case-control study from Channing Laboratory in Boston reviewed plasma carotenoid levels in 969 breast cancer cases and matched controls, and found a significant inverse association between cancer incidence and levels of total carotenoids, alpha-carotene, beta-carotene and lutein/zeaxanthin.⁶⁶ And an analysis of seven cohort studies on carotenoid intake and lung cancer risk found an inverse association between lung cancer and betacryptoxanthin intake.⁶⁷

Individual carotenoids have been investigated for their impact on antioxidant systems. For example, a study at the University of Vienna, Austria, examined whether increasing doses of beta-carotene supplements influenced markers of lipid peroxidation in 42 healthy subjects.⁶⁸ Plasma beta-carotene levels increased significantly in a dose-dependent manner without adverse biological effects; only the highest dose (40 mg/d) protected against oxidative stress, leading the researchers to conclude beta-carotene’s benefits in healthy individuals may be limited. In addition, there continues to be some concern regarding beta-carotene’s possible pro-oxidant activity in smokers, which researchers from Maastricht University, The Netherlands, suggested could be attributed to beta-carotene’s generating ROS that could adversely impact DNA.⁶⁹

More positive overall results have been reported with lycopene, particularly in relation to cardiovascular disease. A review from the University of Toronto noted studies have shown ingestion of lycopene prevents oxidation of LDL and appears to protect against coronary heart disease and myocardial infarction.⁷⁰ In vitro work has shown tomato lycopene is able to prevent induced LDL oxidation, with tomato oleoresin exhibiting significantly greater activity than pure lycopene.⁷¹

Intervention studies using tomato products have also shown positive results. A study at the National Institute for Agronomic Research in Saint-Genes Champanelle, France, included 20 healthy females who received 96 g/d tomato puree in addition to their regular diet.⁷² Supplementation significantly increased plasma lycopene, beta-carotene and lutein, and plasma total antioxidant capacity was positively related to the status of lycopene. Researchers at the University of Milan, Italy, reported daily intake of a beverage with natural tomato extract (Lyc-O-Mato® from LycoRed) by 26 healthy subjects significantly increased plasma carotenoid levels and reduced DNA damage in lymphocytes subjected to oxidative stress.⁷³ The researchers reported similar results in a study in which 12 healthy females consumed a diet enriched with tomato products providing 8 mg/d lycopene; the intervention increased lycopene concentration in plasma and lymphocytes, and improved protection from DNA oxidative damage.⁷⁴

One of the newer carotenoids drawing attention is astaxanthin. A research review from Mera Pharmaceuticals, Kailua-Kona, Hawaii, noted astaxanthin has strong antioxidant activity including protection from UV radiation.⁷⁵ Researchers from the International Research Center for Traditional Medicine in Toyama Prefecture, Japan, reported results from a study in ischemic rats that found astaxanthin showed significant neuroprotective effects.⁷⁶ And researchers at Japan’s National Institute of Health and Nutrition reported astaxanthin significantly inhibited LDL oxidation both in vitro and ex vivo.⁷⁷

Astaxanthin also appears to affect inflammation through antioxidant activity. In a study conducted at the Hokkaido University Graduate School of Medicine, Sapporo, Japan, researchers induced eye inflammation in rats to test the efficacy of astaxanthin, and found the carotenoid suppressed the development of the inflammatory condition in a dose-dependent fashion.⁷⁸ The researchers suggested the activity was due to suppression of TNF-alpha production and blockage of nitric oxide synthase enzyme activity. Additional research on the antioxidant activity of astaxanthin has shown its ability to suppress serum levels of nitric oxide and inflammatory cytokines.⁷⁹

The xanthophylls lutein and zeaxanthin have also been studied for their antioxidant properties, primarily in relation to eye health. A review from Kemin Health noted lutein acts to quench and scavenge photo-induced ROS in the eye, preventing the progression of AMD or cataracts.⁸⁰ The review further noted lutein and zeaxanthin appear to be incorporated into both LDL and high-density lipoprotein (HDL), protecting cholesterol fractions against oxidation. Researchers from Tufts University, Boston, noted by augmenting the macular pigment, lutein and zeaxanthin protect the photoreceptor cell layer from light damage by ROS.⁸¹

Specialty Compounds

There are also a host of specialty compounds that serve as antioxidants in the body. One of the powerful endogenous antioxidants is copper, zinc-superoxide dismutase (CuZn-SOD), which works to catalyze the oxidation and reduction of certain small molecules.⁸² As oral delivery of antioxidant enzymes is limited by digestive process, augmentation of SOD levels has been difficult to achieve. However, a recent study conducted at Universitatsklinikum Ulm, Germany, investigated the ability of a plant-sourced SOD with wheat gliadin (as GliSODin® from P.L. Thomas) to prevent hyperbaric oxidative cell stress.⁸³ In the double blind, randomized study, 20 healthy volunteers were given pure oxygen in a hyperbaric chamber to induce oxidative stress. The subjects given the plant-sourced SOD had significantly lower cellular DNA damage as evidenced by the comet assay and also showed reduced levels of isoprostane, a marker of oxidative stress. Additional research has shown the ability of 1,500 mcg/d of plantsourced SOD (as GliSODin) prior to extreme exercise to decrease exercise-induced lactase release and inhibit oxidative stress.⁸⁴

Another endogenous antioxidant enzyme known for its free radical scavenging ability is glutathione peroxidase, with glutathione, the watersoluble cofactor of the enzyme. Glutathione is synthesized in the body from three amino acids—cysteine, glutamine and glycine—and production tends to decrease with age.

An imbalance in the expression of glutathione peroxidase is associated with several degenerative conditions, according to a research review from the Fox Chase Cancer Center in Philadelphia.⁸⁵ Supplementation with glutathione precursors may help restore glutathione levels and prevent free radical damage; one such compound is the amino acid glutamine. Researchers at the University of Arkansas, Little Rock, found glutamine supplementation increased glutathione production and significantly reduced tumor development in animal models of breast cancer.^86,87

Additional research has investigated the benefits of nonnutritive components in cruciferous vegetables, including the glucosinolate hydrolysis products—sulforaphane and indole-3-carbinol, which researchers from the U.S. Department of Agriculture (USDA) suggest protect against ROS, alter detoxification by inducing phase II enzyme activity and decrease carcinogen activation.⁸⁸ Research from the Spanish Council for Scientific Research in Madrid noted indoles react nonspecifically and quench free radicals at physiological pH levels.⁸⁹

Further research on a trademarked source of sulforaphane’s glucosinolate precursor, glucoraphanin (SGS™ glucosinolate from CS Agra) has been conducted at Johns Hopkins in Boston. A study using human adult retinal pigment epithelial cells found treatment with glucoraphanin (as SGS) markedly reduced oxidative toxicity through phase II enzyme induction, with protection persisting even after removal of the compound.⁹⁰ In addition to identifying the mechanism of action, Johns Hopkins researchers also determined the best source of glucoraphanin was younger broccoli sprouts, as three-day-old sprouts had 10 to 100 times the level of the desired compound, while also having almost none of the less desirable indole glucosinolates.⁹¹

Similar findings on the variability of beneficial compounds was reported by scientists at the University of Illinois at Urbana- Champaign.⁹² They compared the antioxidant capacity of hydrophilic and lipophilic extracts from eight broccoli genotypes and found significant variability in antioxidant capacity which could not be attributed to flavonoid content or ascorbic acid in the hydrophilic extracts.

An additional beneficial antioxidant compound is the natural hormone melatonin. Levels of this hormone decline gradually over the life span, which researchers suggest may be associated with reduced antioxidant protection in the elderly.⁹³ A review from the University of Texas Health Science Center, San Antonio, noted melatonin can directly neutralize toxic reactants and stimulate antioxidant enzymes.⁹⁴ Furthermore, several metabolites that form when melatonin neutralizes ROS are themselves free radical scavengers. In addition, melatonin appears to preserve the integrity of the mitochondria under stress to help maintain cell function and survival.⁹⁵

The antioxidant capacity of melatonin was investigated by Tufts University researchers, who compared its activity against glutathione, vitamin C and vitamin E.⁹⁶ Melatonin was found to be a universal antioxidant with greater activity than any of the comparative compounds. Melatonin has been further shown by Turkish researchers to prevent oxidative damage associated with ischemia-reperfusion injury in rats, while also restoring levels of endogenous antioxidant enzymes.⁹⁷ Another study from Egypt found administration of melatonin protected against induced cardiac toxicity in rats through its antioxidant and free radical scavenging activity.⁹⁸

Producers of dietary supplements have the opportunity to bring balance to the oxidation/antioxidant systems by contributing to Mother Nature’s supply of protective ingredients. Providing scientifically supported, efficacious formulas backed by responsible marketing can enhance consumers’ choices in a quest for a lifetime of good health.

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