Antioxidant

From Wikipedia, the free encyclopedia

This article or section is in need of attention from an expert on the subject.
WikiProject Molecular and Cellular Biology or the Molecular and Cellular Biology Portal may be able to help recruit one.
If a more appropriate WikiProject or portal exists, please adjust this template accordingly.

This article contains unencyclopedic lists that may require cleanup.
To meet Wikipedia's quality standards, please help improve this article by: removing items which are not notable, encyclopedic, or helpful from embedded lists; incorporating appropriate items into the main body of the article; and discussing this issue on the talk page.
Certain foods are rich sources of antioxidants.
Enlarge
Certain foods are rich sources of antioxidants.

An antioxidant is a chemical that reduces the rate of particular oxidation reactions in a specific context, where oxidation reactions are chemical reactions that involve the transfer of electrons from a substance to an oxidizing agent, this generally results in different chemicals to the original ones.

Antioxidants are particularly important in the context of organic chemistry and biology. All living organisms maintain a reducing environment inside their cells, all cells contain complex systems of antioxidants to prevent chemical damage to the cells' components by oxidation. These antioxidants include glutathione and ascorbic acid and are substrates for enzymes such as peroxidases and oxidoreductases.

Antioxidants are widely used as ingredients in dietary supplements used for health purposes such as preventing cancer and heart disease. Studies have suggested antioxidant supplements has benefits for health, but several large clinical trials did not demonstrate a definite benefit for the formulations tested, and excess supplementation may even be harmful.

Dietary supplementation has few specific antioxidants compared to a broad diet rich in phytonutrients, which will yield thousands of different polyphenol antioxidants available for metabolism.

Contents

[edit] History

The term antioxidant (also "antioxygen") originally referred specifically to a chemical that prevented the consumption of molecular oxygen. In the 19th and early 20th century, antioxidants were the subject of extensive research in industrial processes such as the corrosion of metals, explosives, the vulcanization of rubber, and the knocking of fuels in internal combustion engines.[1]

Early nutrition researchers focused on the use of antioxidants for preventing the oxidation of unsaturated fats, the cause of rancidity. Antioxidant activity could be measured simply by placing the fat in a closed glass container with oxygen and observing the rate of oxygen consumption. However, it was the identification of vitamins A, C, and E as antioxidants that revolutionized the field and led to the realization of the importance of antioxidants in biology.

The possible mechanisms of action of antioxidants were first explored thoroughly by Moreau and Dufraisse (1926), who recognized that a substance with anti-oxidative activity is likely to be one that is itself a target for oxidation. Research into how vitamin E prevents the process of lipid peroxidation led to the current understanding of antioxidants as reducing agents that break oxidative chain reactions, often by scavenging reactive oxygen species before they can cause damage to the cells.[2]

[edit] Biology

All living organisms contain complex systems of antioxidant enzymes and chemicals, some to combat oxidative damage to cellular components and others to regulate and sustain natural cellular processes such as oxidative phosphorylation and the formation of disulfide bonds.

[edit] Oxidative damage

One major action of antioxidants in cells is to prevent damage due to the action of reactive oxygen species. Reactive oxygen species include hydrogen peroxide (H2O2), hypochlorous acid (HOCl) , and free radicals such as the hydroxyl radical (·OH) and the superoxide anion (O2−).[3] These molecules are unstable and highly reactive, and can damage cells by chemical chain reactions such as lipid peroxidation, or formation of DNA adducts that can lead to oncogenic mutations or cell death if not reversed by DNA repair mechanisms. All cells therefore contain antioxidants that serve to reduce or prevent this damage.

[edit] ATP generation and cellular maintenance

Antioxidants are especially important in the mitochondria of eukaryotic cells, since the use of oxygen as part of the process for generating energy produces reactive oxygen species. The process of aerobic metabolism requires oxygen because it serves as the final resting place for electrons generated by the oxidation steps of the citric acid cycle (i.e. oxygen is the final "electron acceptor" of the redox reactions). However, the superoxide anion is produced as a by-product of this reduction of oxygen in the electron transport chain. Specifically, the reduction of coenzyme Q in complex III is a major source of superoxide anion, since a highly reactive free radical is formed as an intermediate (Q·−). This unstable radical can lead to electron "leakage"; instead of moving along the well-controlled reactions of the electron transport chain, the electrons jump directly to molecular oxygen, forming the superoxide anion.[4]

The redox state of the cell's interior is tightly regulated. The cytoplasm is a reducing environment; however, proteins synthesized for secretion often must be oxidized - particularly to form disulfide bonds between cysteine residues - before export, which normally takes place in the endoplasmic reticulum and Golgi apparatus.

The thioredoxin system contains the 12-kDa protein thioredoxin and its companion thioredoxin reductase. Thioredoxin is present in all sequenced organisms except Tropheryma whipplei (the bacteria that cause Whipple's disease).[5] The active site of thioredoxin consists of two neighboring cysteines, as part of a highly conserved CXXC motif, that can cycle between an active dithiol form (reduced) and an oxidized disulfide form. In its active state, thioredoxin acts as an efficient reducing agent, scavenging reactive oxygen species and maintaining other proteins in their reduced state. After being oxidized, the active thioredoxin is regenerated by the action of thioredoxin reductase, and thioredoxin reductase is in turn reduced by NADPH.[6]

The glutathione system includes glutathione, glutathione reductase, and glutathione peroxidase. Glutathione peroxidase is an enzyme with four selenium-containing groups that catalyze the breakdown of hydrogen peroxide and protects lipids in cell walls from peroxidation. There are at least four different glutathione peroxidase genes in animals. Glutathione peroxidase 1 is the most aboudant and is a very efficient scavenger of H2O2, while glutathione peroxidase 4 is mainly a scavenger of lipid hydroperoxides. Glutathione is absolutely nescessary for animal life; mice genetically engineered to be deficient in glutathione biosynthesis die before birth. However, glutathione peroxidase 1 is dispensable for life: mice genetically engineered to lack this enzyme have a normal lifespan.

Superoxide dismutase (SOD) is a class of closely related enzymes that catalyse the breakdown of the highly reactive superoxide anion into oxygen and hydrogen peroxide. SOD proteins are present in almost all aerobic cells and in extracellular fluids. Each molecule of superoxide dismutase contains atoms of copper, zinc, manganese or iron. SOD that is formed in the mitochondria contains manganese (MnSOD). This SOD is synthesized in the matrix of the mitochondria. SOD that is formed in the cytoplasm of the cell contains copper and zinc (CuZnSOD). There also exists a third form of SOD in extracellular fluids, termed EC-SOD (also containg Copper and Zinc at the active sites). MnSOD seems to be the most biologically important of these three since mice lacking this gene die soon after birth. Mice lacking CuZnSOD have a shortned lifespan, while EC-SOD lacking mice have minimal defects.[7]

Catalase is a widely occurring enzyme containing four iron atoms in a 500 amino acid protein. Catalase catalyses the conversion of hydrogen peroxide to water and oxygen at rates of up to 6,000,000 molecules per minute. Catalase has a secondary role oxidising toxins including formaldehyde, formic acid and alcohols. The exact role of catalase in animals is still debated since humans with genetic deficiency of catalase ("acatalesemia") suffer few ill effects and genetic deletion of the catalase in gene in mice is not detrimental either.

Peroxiredoxins catalyze the reduction of hydrogen peroxide, alkyl peroxides, hydroperoxides as well as peroxynitrite. There are presently six different peroxiredoxins known. Genetic ablation of peroxiredoxin 1 or 2 causes shortned lifespan and hemolytic anemia in mice.

[edit] Applications in nutrition and medicine

[edit] Health preservation

Antioxidants are chemicals that reduce oxidative damage to cells and biomolecules. Researchers have found a high correlation between oxidative damage and the occurrence of disease.[citation needed] For example, low density lipoprotein (LDL) oxidation is associated with cardiovascular disease. The process leading to atherogenesis, atherosclerosis, and cardiovascular disease is complex, involving multiple chemical pathways and networks, but the precursor is LDL oxidation by free radicals, resulting in inflammation and formation of plaques.

Research suggests that consumption of antioxidant-rich foods reduces damage to cells and biochemicals from free radicals.[citation needed] This may slow down, prevent, or even reverse certain diseases that result from cellular damage, and perhaps even slow down the natural aging process. This is the basis for the free-radical theory of aging.

Some of the reactions in the body that produce free radicals involve metal ions. Some antioxidants, such as the tannins in walnuts and tea, chelate (wrap around) metal ions. This not only reduces the formation of ion-dependent free radicals, but also prevents the metal ions from oxidizing cells and biochemicals directly.

Some studies suggest that by destroying free radicals and reducing cellular damage, antioxidants in the diet can have positive health effects, such as preventing macular degeneration (studied in the Age-Related Eye Disease Study);[8] maintaining the immune system;[9] potentially preventing neurodegeneration due to oxidative stress;[10] preventing DNA damage;[11] and lowering the risk of cardiovascular disease.[12] Any specific antioxidant may perform only a small fraction of these functions. The mixed results from controlled studies using antioxidant vitamins suggest that other antioxidant substances in fruit and vegetables at least partially explain the better health of those who consume more fruit and vegetables.[13] Dietary antioxidants are not the primary antioxidant inside the body, and there are still many questions as to how polyphenols and other dietary antioxidants protect cells and biochemicals from oxidation. Some antioxidants preserve, or even recycle, other antioxidants such as vitamin E.

[edit] Adverse effects

Relatively strong reducing acids can have anti-nutritional effects by binding to dietary minerals in the gastrointestinal tract and preventing them from being absorbed. Notable examples are oxalic acid and phytic acid, which are high in plant-based diets. Some tannins also have this negative characteristic. Calcium and iron deficiencies are not uncommon in mideastern diets where there is high consumption of phytic acid present in beans and unleavened whole grain bread. These anti-nutrients can result in deceptively high oxygen radical absorbance capacity (ORAC) ratings given to various "healthy" beverages and foods, particularly:

Foods Reducing acid
Cocoa and chocolate, spinach, and berries Oxalic acid
Whole grains, maize Phytic acid
Tea Tannins

Other extremely powerful nonpolar antioxidants such as eugenol also happen to have toxicity limits that can easily be exceeded with the misuse of essential oils.

While antioxidants supplementation is widely hypothesized to prevent the development of cancer, antioxidants may, paradoxically, interfere with cancer treatments.[14] One explanation for this effect is that the growth-promoting environment of cancer cells leads to high levels of redox stress under baseline conditions, and this makes cancer cells more susceptible than normal cells to the further stress of chemotherapy or radiation therapy. So by reducing the redox stress in cancer cells, antioxidant supplements could decrease the effectiveness of the therapy designed to kill them.

[edit] Calorie restriction

Virtually all studies of mammals have concluded that a restricted calorie diet (CR) extends median and maximum lifespan (CR is almost the only protocol to have achieved this). This benefit appears to be at least partly due to substantially reduced oxidative stress.[15] As food produces free radicals (oxidants) when metabolized, antioxidant-rich diets are thought to stave off the effects of aging significantly better than diets lacking in antioxidants.

[edit] Physical exercise

During exercise, oxygen consumption can temporarily increase by a factor of more than 10.[16] This leads to a temporary large increase in the production of oxygen free radicals, resulting in increased cell damage contributing to muscular fatigue during and after exercise. The body uses antioxidants to reduce the amount of such damage. The inflammatory response that occurs after strenuous exercise is also associated with increased occurrence of free radicals, especially during the 24 hours after an exercise session. In this phase too, antioxidants in the body reduce the damage. The immune system response to damage done by exercise peaks 2 to 7 days after exercise, the period during which adaptation resulting in greater fitness is greatest. During this process, free radicals are used by neutrophils in the immune system to identify damaged tissue. As a result, excessive antioxidant levels have the potential to inhibit recovery and adaptation mechanisms.[17]

There is a popular view that those who undertake vigorous exercise can benefit from increased consumption of antioxidants, but an examination of the literature finds support that this is the case only for certain antioxidants at certain levels, and some evidence that very large intake of some antioxidants may be detrimental to recovery from exercise. There is strong evidence that one of the adaptations that result from exercise is a strengthening of the body's antioxidant defenses, particularly the glutathione system, to deal with the increased oxidative stress.[18] It is possible that this effect may be to some extent protective against diseases which are associated with oxidative stress, which would provide a partial explanation for the lower incidence of major diseases and better health of those who undertake regular exercise.

The antioxidant system that protects lipid membranes from free radicals includes vitamin E, beta-carotene, vitamin A, and coenzyme Q10. The system that scavenges free radicals in the water based cytoplasm includes vitamin C, glutathione peroxidase, superoxide dismutase, and catalase. The effect of each of the exogenous antioxidants needs to be examined separately, although they work in a co-operative manner.

The body of research suggests no benefits from supplementing with vitamin A above normally recommended levels. Recent well-designed studies suggest there are no ergogenic benefits from vitamin E (except for those who do exercise at high altitude)[19][20][21] despite its key role in preventing lipid membrane peroxidation. For example, 6 weeks of vitamin E supplementation had no effect on muscle damage indicators in ultramarathon runners.[22] Although selenium is essential to the glutathione antioxidant system which, as mentioned above, is upregulated by exercise, there is no evidence that supplementation with selenium above the RDA is of any ergogenic benefit. However, for vitamin C there is considerable evidence that vitamin C requirements are greater in those who do vigorous exercise, with plasma levels falling with intake of 100mg (well over the accepted RDA) and around 300mg per day being required to maintain blood plasma levels.[23] There is some evidence that supplementation with vitamin C increased the amount of intense exercise that can be done, and lowered the heart rate while doing it (which is indicative of greater efficiency),[24] and that vitamin C supplementation before strenuous exercise reduces the amount of muscle damage.[25] However, some other studies found no such effects, and some research suggests that supplementation with amounts as high as 1000 mg inhibits recovery,[26] although the very short pre-exercise supplementation period in this study may have influenced the results. There is strong evidence that vitamin C supplementation reduces upper respiratory tract infections in ultra-endurance athletes.[27]

In summary, a diet with at least 300 mg of vitamin C is of benefit to those who undertake high intensity or high volume exercise, but it is not clear that normal requirements for vitamin A, vitamin E or selenium are increased.

[edit] Clinical trials

Although some levels of antioxidant vitamins and minerals in the diet are required for good health, there is considerable doubt as to whether antioxidant supplementation is beneficial, and if so, which and what amount of antioxidant(s) are optimal.

One study of lung cancer patients found that those given beta-carotene supplements had worse prognoses. Two 1994 studies found an increased rate of lung cancer in smokers supplementing with beta carotene. This is believed to be due to antioxidant interference with the body's normal use of localised free radicals e.g. nitric oxide for cell signalling. Due to the complex nature of the interactions of antioxidants with the body, it is difficult to interpret the results of many experiments. In vitro testing (outside the body) has shown many natural antioxidants, in specific concentration, can halt the growth of or even kill cancerous cells.

In the early 1990s, it was hypothesized that oxidation of LDL cholesterol contributes to heart disease, and several observational studies found that people taking Vitamin E supplements had a lower risk of developing heart disease..[28] Taken together, this led researchers to conduct at least seven large clinical trials testing the effects of antioxidant supplement with Vitamin E, in doses ranging from 50 to 600 mg per day. However, none of these trials found a statistically significant effect of Vitamin E on overall number of deaths or on deaths due to heart disease.[29]

While several trials have investigated supplements with high doses of antioxidants, the "Supplémentation en Vitamines et Mineraux Antioxydants" (SU.VI.MAX) study tested the effect of supplementation with doses comparable to those in a healthy diet.[30] Over 12,500 French men and women took either low-dose antioxidants (120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 μg of selenium, and 20 mg of zinc) or placebo pills for an average of 7.5 years. The investigators found there was no statistically significant effect of the antioxidants on overall survival, cancer, or heart disease. However, a subgroup analysis showed a 31% reduction in the risk of cancer in men, but not women. The authors interpreted these results as suggesting that "an adequate and well-balanced supplementation of antioxidant nutrients, at doses that might be reached with a healthy diet that includes a high consumption of fruits and vegetables, had protective effects against cancer in men."

[edit] Measurement

Oxygen radical absorbance capacity (ORAC) has become the current industry standard for assessing antioxidant strength of whole foods, juices and food additives.[31] Other measurement tests include reducing power, free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating.[32]

[edit] Food preservatives

Antioxidants used as food additives to help guard against food deterioration include:

[edit] Food Sources

See also List of antioxidants in food

Antioxidants are found naturally in varying amounts, in vegetables, fruits, grain cereals, legumes, nuts etc. Antioxidant sources [33] include:

  • Fruits: berries
  • Vegetables: peppers and spinach.
  • Fungi: mushrooms
  • Whole grain cereals: barley, millet and maize.
  • Nuts: pecans, pistachios, and almonds [34]
  • Cocoa products: chocolate.
  • Drinks: Coffee, wines, and teas .

[edit] Dietary supplements

See also List of phytochemicals and foods in which they are prominent

Since the discovery of vitamins, it has been recognized that antioxidants from the diet are essential for healthful lives in humans and many other mammals. More recently, a large body of evidence has accumulated that suggests supplementation of the diet with various kinds of antioxidants can improve health and extend life. Many nutraceutical and health food companies now sell formulations of antioxidants as dietary supplement. These supplements may include specific antioxidant chemicals, like resveratrol (from grape seeds), combinations of antioxidants, like the "ACES" products that contain beta carotene (provitamin A), vitamin C, vitamin E and Selenium, or specialty herbs that are known to contain antioxidants such as green tea and jiaogulan.

[edit] In fuels

Some antioxidants are added to liquid industrial chemicals, most often fuels and lubricants to prevent oxidation, and in gasolines to prevent polymerization leading to gumming. Some examples are:

Antioxidants are frequently used together with metal deactivators and corrosion inhibitors.

[edit] See also


[edit] Further reading

Exercise and antioxidants

[edit] External links

[edit] References

  1. ^ Matill HA (1947). "Antioxidants". Annu Rev Biochem 16: 177-192.
  2. ^ Wolf G (2005). "The discovery of the antioxidant function of vitamin E: the contribution of Henry A. Mattill". J Nutr 135 (3): 363-6. PMID 15735064.
  3. ^ Barry Halliwell, Free Radicals and Other Reactive Species in Disease, Encyclopedia of Life Sciences (2005)
  4. ^ Finkel T, Holbrook NJ (2000). "Oxidants, oxidative stress and the biology of ageing". Nature 408 (6809): 239-47. PMID 11089981.
  5. ^ Raoult D, Ogata H, Audic S, Robert C, Suhre K, Drancourt M, Claverie J (2003). "Tropheryma whipplei Twist: a human pathogenic Actinobacteria with a reduced genome.". Genome Res 13 (8): 1800-9. PMID 12902375.
  6. ^ Nordberg J, Arner ES (2001). "Reactive oxygen species, antioxidants, and the mammalian thioredoxin system". Free Radic Biol Med 31 (11): 1287-312. PMID 11728801.
  7. ^ Halliwell B (1999). "Antioxidant defence mechanisms: from the beginning to the end (of the beginning).". Free Radic Res 31 (4): 261-72. PMID 10517532.
  8. ^ Age-Related Eye Disease Study Research Group. (2000). The Age-Related Eye Disease Study: A Clinical Trial of Zinc and Antioxidants—Age-Related Eye Disease Study Report No. 2 J Nutr 130:1516S-1519S.
  9. ^ Nantz MP, Rowe CA, Nieves C Jr, Percival SS. (2006). Immunity and antioxidant capacity in humans is enhanced by consumption of a dried, encapsulated fruit and vegetable juice concentrate. J Nutr 136(10):2606-10.
  10. ^ Wang JY, Wen LL, Huang YN, Chen YT, Ku MC. (2006). Dual effects of antioxidants in neurodegeneration: direct neuroprotection against oxidative stress and indirect protection via suppression of glia-mediated inflammation. Curr Pharm Des 12(27):3521-33.
  11. ^ Hillestrom PR, Covas MI, Poulsen HE. (2006). Effect of dietary virgin olive oil on urinary excretion of etheno-DNA adducts. Free Radic Biol Med 41(7):1133-8.
  12. ^ Covas MI, Nyyssonen K, Poulsen HE, Kaikkonen J, ZunftHJ, Kiesewetter H, Gaddi A, de la Torre R, Mursu J, Baumler H, Nascetti S, Salonen JT, Fito M, Virtanen J, Marrugat J. EUROLIVE Study Group. (2006). The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial. Ann Intern Med 145(5):333-41.
  13. ^ Cherubini A, Vigna GB, Zuliani G, Ruggiero C, Senin U, Fellin R. (2005). "Role of antioxidants in atherosclerosis: epidemiological and clinical update". Curr Pharm Des 11 (16): 2017-32.  abstract.
  14. ^ Schumacker P (2006). "Reactive oxygen species in cancer cells: Live by the sword, die by the sword.". Cancer Cell 10 (3): 175-6. PMID 16959608.
  15. ^ G. López-Lluch, N. Hunt, B. Jones, M. Zhu, H. Jamieson, S. Hilmer, M. V. Cascajo, J. Allard, D. K. Ingram, P. Navas, and R. de Cabo (2006). "Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency". Proc Natl Acad Sci U S A 103 (6): 1768–1773.  abstract.
  16. ^ Dekkers JC, van Doornen LJ, Kemper HC (1996). "The role of antioxidant vitamins and enzymes in the prevention of exercise-induced muscle damage". Sports Med 21 (3): 213-238.  abstract.
  17. ^ Tiidus, P.M. (1998). "Radical species in inflammation and overtraining". Can J Physiol Pharmacol 76 (5): 533-8.  abstract.
  18. ^ Leeuwenburgh C, Fiebig R, Chandwaney R, Ji LL. (1994). "Aging and exercise training in skeletal muscle: responses of glutathione and antioxidant enzyme systems". Am J Physiol 267 (2 Pt 2): R439-45.  abstract.
  19. ^ Tiidus PM, Houston ME (1995). "Vitamin E status and response to exercise training". Sports Med 20 (1): 12-23.  abstract.
  20. ^ Viitala P, Newhouse IJ. (2004). "Vitamin E supplementation, exercise and lipid peroxidation in human participants". Eur J Appl Physiol 93 (1-2): 108-15.  abstract.
  21. ^ Mehdani M, Fielding RA, Fotouhi N, Vitamin E. chapter 10 in Sports Nutrition Vitamins and Trace Minerals. Edited by Ira Wolinsky and Judy A. Driskell. New York: CRC Press, 1997, 119-131
  22. ^ Mastaloudis A, Traber MG, Carstensen K, Widrick JJ (2006). "Antioxidants did not prevent muscle damage in response to an ultramarathon run". Med Sci Sports Exerc 38 (1): 72-80.  abstract.
  23. ^ Keith, R.E. Ascorbic Acid. chapter 2 in Sports Nutrition Vitamins and Trace Minerals. Edited by Ira Wolinsky and Judy A. Driskell. New York: CRC Press, 1997, p. 29-45.
  24. ^ Howald H, Segesser B, Korner WF (1975). "Ascorbic acid and athletic performance". Ann N Y Acad Sci. 258: 458-64.  abstract.
  25. ^ Jakeman P, Maxwell S. (1993). "Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise". Eur J Appl Physiol Occup Physiol 67 (5): 426-30.  abstract.
  26. ^ Close GL, Ashton T, Cable T, Doran D, Holloway C, McArdle F, MacLaren DP. (2006). "Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process". Br J Nutr 95 (5): 976-81.  abstract.
  27. ^ Peters EM, Goetzsche JM, Grobbelaar B, Noakes TD. (1993). "Vitamin C supplementation reduces the incidence of postrace symptoms of upper-respiratory-tract infection in ultramarathon runners". Am J Clin Nutr 57 (2): 170-4.  abstract.
  28. ^ *Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC (1993). "Vitamin E consumption and the risk of coronary heart disease in men". N Engl J Med 328 (20): 1450-6. PMID 8479464.
  29. ^ Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ (2003). "Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials". Lancet 361 (9374): 2017-23. PMID 12814711.
  30. ^ *Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D, Roussel AM, Favier A, Briancon S (2004). "The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals". Arch Intern Med 164 (21): 2335-42. PMID 15557412.
  31. ^ Wu, X., G.R. Beecher, J.M. Holden, D.B., Haytowitz, S.E. Gebhardt, and R.L. Prior (2004). "Lipophilic and Hydrophilic Antioxidant Capacities of Common Foods in the United States." J Agric Food Chem 52:4026-37 PMID 15186133
  32. ^ Gulcin I., Kufrevioglu O.I., Oktay M., Buyukokuroglu M.E. "Antioxidant, antimicrobial, antiulcer and analgesic activities of nettle" J Ethnopharmacol 2004; 90:205-215 PMID: 15013182
  33. ^ http://www.dietaryfiberfood.com/antioxidant-food.php
  34. ^ X. Wu, L. Gu, J. Holden, D.B. Haytowitz, S.E. Gebhardt, G. B. and R.L. Prior (2004). "Development of a database for total antioxidant capacity in foods: a preliminary study. Journal of Food Composition and Analysis". J Food Composition and Analysis 17: 407-422..
Retrieved from "http://en.wikipedia.org../../../a/n/t/Antioxidant.html"