Nutrient Highlight: Super Antioxidant
Antioxidant References

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Vitamin A

• The risk of breast cancer approximately doubled among subjects with blood levels of beta-carotene at the lowest quartile, as compared with those at the highest quartile. The odds ratio for the lower quartile of total carotenoids was 2.31. These observations offer evidence that a low intake of carotenoids, through poor diet and/or lack of vitamin supplementation, may be associated with increased risk of breast cancer and may have public health relevance for people with markedly low intakes.
  **Serum carotenoids and breast cancer. Am J Epidemiol 2001 Jun 15;153(12):1142-1147
• Dietary beta carotene reduces the risk of lung cancer in nonsmoking men and women.
  **Dietary beta carotene and lung cancer risk in U.S. nonsmokers. J Natl Cancer Inst 1994 Jan 5;86(1):33-8
• Healthy centenarians show a particular profile in which high levels of vitamin A and] vitamin E seem to be important in guaranteeing their extreme longevity.
  **Plasma antioxidants and longevity: a study on healthy centenarians. Free Radic Biol Med 2000 Apr 15;28(8):1243-1248

• In an animal study, a preparation containing both beta-carotene and licorice root powder markedly increased antioxidant activity of the liver.
  **Antioxidant activity of parapharmaceutics containing natural inhibitors of free radical processes. Bull Exp Biol Med 2000 Jul;130(7):658-660

• Research suggests that the risk of developing colorectal adenomas is reduced in those with high vitamin A levels. Serum concentrations of vitamin A were significantly inversely related to the risk of colorectal adenoma when cases were compared with control groups. After adjustment for energy intake, smoking, alcohol, estrogen therapy, body-mass-index and social class the inverse association between vitamin A and colorectal adenoma was even more marked.
  **Relation of serum antioxidant vitamins to the risk of colorectal adenoma. Digestion 2001;63(1):43-48

• Retinoic acid (RA), a form of Vitamin A, has been shown to exert antiapoptotic and antioxidative activity in various cells. In this animal study, the authors determined that RA reduced staurosporine-induced oxidative stress and cell death by preventing the decrease in the protein levels of superoxide dismutase 1 and 2, thus supporting the antioxidant defense system.
   **Retinoic acid reduces apoptosis and oxidative stress by preservation of SOD protein level. Free Radic Biol Med 2001 May 15;30(10):1067-1077

• Vitamin A may boost immune responses in the elderly, persons with high exposure to ultraviolet light, patients who have undergone surgery, and persons with parasitic infection. Vitamin A supplementation reduces mortality and complications resulting from measles.
  **Vitamin A as an immunomodulating agent. Clin Pharm 1993 Jul;12(7):506-14

• All the antioxidant vitamins A, C, and E significantly decrease lipid peroxide levels and oxidant load in coronary heart disease patients.
  **Comparison of antioxidant efficacy of vitamin E, vitamin C, vitamin A and fruits in coronary heart disease: a controlled trial. J Assoc Physicians India 2001 Mar;49:327-331

• Epidemiological studies link low serum beta-carotene levels to elevated risk of lung and other cancers.
  **Protection by beta-carotene and related compounds against oxygen-mediated cytotoxicity and genotoxicity: implications for carcinogenesis and anticarcinogenesis. Free Radic Biol Med 1992 Oct;13(4):407-33
• In intervention trials, beta-carotene diminishes precancerous lesions.
  **Protection by beta-carotene and related compounds against oxygen-mediated cytotoxicity and genotoxicity: implications for carcinogenesis and anticarcinogenesis.   Free Radic Biol Med 1992 Oct;13(4):407-33

• This study provides further epidemiological evidence of a protective role of high alpha- and beta- carotene in early atherogenesis. Alpha- and beta- carotene plasma levels were inversely associated with the prevalence of atherosclerosis in the carotid and femoral arteries and with the 5-year incidence of atherosclerotic lesions in the carotid arteries.
  **High plasma levels of alpha- and beta-carotene are associated with a lower risk of atherosclerosis: results from the Bruneck study. Atherosclerosis 2000

• A mixed antioxidant containing beta-carotene (Vitamin A), alpha-tocopherol (Vitamin E), ascorbic acid (Vitamin C), grape seed catechins, and milk thistle derived silybin suppressed lipid peroxidation and protected membrane proteins against degradation induced by peroxyl radicals, and effectively delayed AAPH induced haemolysis.
  **Oxidative insult to human red blood cells induced by free radical initiator AAPH and its inhibition by a commercial antioxidant mixture.  Life Sci 2001 May 25;69(1):75-86

Vitamin C

• Vitamin C (ascorbate) is toxic to tumour cells, and has been suggested as an adjuvant cancer treatment.
  **Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours. Br J Cancer 2001 Jun 1;84(11):1544-50
• In a study designed to assess the potential clinical efficacy of Vitamin C in treating SW620 hollow fibre tumours, 2-day treatments with 10 ascorbate increased the percentage of apoptotic cells. Lipoic acid synergistically enhanced the ascorbate's tumoricidal action.
  **Ibid.

• Helicobacter pylori infection in humans is associated with chronic type B gastritis, peptic ulcer disease, and gastric carcinoma. In this study mice inoculated with H. pylori and treated with vitamin C showed significantly lower colonization levels and lower inflammation scores than those of untreated or control-meal-treated animals at 1 day and 10 days after the cessation of treatment. Vitamin C showed an inhibitory effect on H. pylori growth in vitro. In conclusion, antioxidants may be a new strategy for treating H. pylori infection in humans.
  **Astaxanthin-rich algal meal and vitamin C inhibit Helicobacter pylori infection in BALB/cA mice. Antimicrob Agents Chemother 2000 Sep;44(9):2452-2457

• The lens and retina of the eye suffer oxidative damage and the anti-oxidant vitamins A, C and E are implicated as protective.
  **Nutrition supplements and the eye. Eye 1998;12 ( Pt 1):127-33
• Ascorbic acid (vitamin C) may help to prevent gallstones.
  **Ascorbic acid and cholesterol gallstones. Med Hypotheses 1993 Feb;40(2):81-4
• Vitamin A, C, and E supplementation is effective in reducing cell proliferation abnormalities of the colorectal mucosa that may indicate a precancerous condition.
  **Effect of vitamin A, C, and E supplementation on rectal cell proliferation in patients with colorectal adenomas. J Natl Cancer Inst 1992 Jan 1;84(1):47-51
• In glaucoma patients Vitamin C in high doses has been found to lower intraocular pressure via its osmotic effect. **Other nutrients holding some potential benefit for glaucoma include lipoic acid, vitamin B12, magnesium, and melatonin.
  **Natural therapies for ocular disorders, part two: cataracts and glaucoma. Altern Med Rev 2001 Apr;6(2):141-66

• Researchers at the University of Rochester have proposed that increased dietary consumption or supplementation of vitamins C and E during pregnancy may reduce physiologically the risks of that portion of preterm premature rupture of membranes.
  **Vitamins C and E: missing links in preventing preterm premature rupture of membranes? Am J Obstet Gynecol 2001 Jul;185(1):5-10

• In a large-scale study examining the association of dietary beta-carotene, vitamin C, and vitamin E with peripheral arterial disease vitamin C intake was significantly inversely associated with peripheral arterial disease in women.
  **Dietary antioxidants and peripheral arterial disease: the Rotterdam Study. Am J Epidemiol 2001 Jul 15;154(2):145-149.

• A mixed antioxidant containing ascorbic acid (Vitamin C), beta-carotene (Vitamin A), alpha-tocopherol (Vitamin E), grape seed catechins, and milk thistle derived silybin suppressed lipid peroxidation and protected membrane proteins against degradation induced by peroxyl radicals, and effectively delayed AAPH induced haemolysis.
  **Oxidative insult to human red blood cells induced by free radical initiator AAPH & its inhibition by a commercial antioxidant mixture. Life Sci 2001 May 25;69(1):75-86

Vitamin E

• Reduced pulmonary function is an important predictor of mortality in the general population, and antioxidant vitamins are thought to positively influence pulmonary function. This study supports the hypothesis that antioxidant vitamins may play a role in respiratory health and that vitamin E and beta-cryptoxanthin appear to be stronger correlates of lung function than other antioxidant vitamins.
  **The relation of serum levels of antioxidant vitamins C and E, retinol and carotenoids with pulmonary function in the general population. Am J Respir Crit Care Med 2001 Apr;163(5):1246-1255

• Early intervention to decrease oxygen consumption by antioxidants such as vitamin E supplement may be of value in preserving renal function in patients at risk for chronic renal failure.
  **Role of lipid peroxidation, trace elements and anti-oxidant enzymes in chronic renal disease patients. J Med Assoc Thai 1996 Dec;79(12):791-800

• Oral treatment with vitamin E improves the antioxidant/oxidant balance in plasma, LDL particles, and red blood cells, and counteracts lipid peroxidation processes in beta-thalassemia intermedia patients.
  **Oral supplements of vitamin E improve measures of oxidative stress in plasma and reduce oxidative damage to LDL and erythrocytes in beta-thalassemia intermedia patients. Free Radic Res 2001 May;34(5):529-540

• Glutathione level is significantly related to vitamin E level, and supplementation with vitamin E (100 IU/day) significantly increases glutathione and lowers lipid peroxidation and HbA1c concentrations in the erythrocytes of type 1 diabetic patients.
  **Vitamin E supplementation restores glutathione and malondialdehyde to normal concentrations in erythrocytes of type 1 diabetic children. Diabetes Care 2000 Sep;23(9):1389-94
• Vitamin E is an antioxidant that has been demonstrated to improve insulin action. Recent evidence suggests that vitamin E enhances glutathione levels and may play a protective role in magnesium deficiency-induced cardiac lesions.
  **Effects of vitamin E and glutathione on glucose metabolism: role of magnesium. Hypertension 1999 Oct;34(4 Pt 2):1002-6
• Antioxidant vitamin E supplementation improved the therapeutic effect of recombinant human erythropoietin (rhEPO) in patients with chronic renal failure on hemodialysis.
  **Vitamin E alleviates the oxidative stress of erythropoietin in uremic children on hemodialysis. Pediatr Nephrol 2000 Jan;14(1):13-7
• Vitamin E is an antioxidant that has been demonstrated to improve insulin action. Recent evidence suggests that vitamin E enhances glutathione levels and may play a protective role in magnesium deficiency-induced cardiac lesions.
  **Effects of vitamin E and glutathione on glucose metabolism: role of magnesium. Hypertension 1999 Oct;34(4 Pt 2):1002-6

• Healthy centenarians show a particular profile in which high levels of vitamin A and vitamin E seem to be important in guaranteeing their extreme longevity.
  **Plasma antioxidants and longevity: a study on healthy centenarians. Free Radic Biol Med 2000 Apr 15;28(8):1243-1248

• Researchers at the University of Rochester have proposed that increased dietary consumption or supplementation of vitamins C and E during pregnancy may reduce physiologically the risks of that portion of preterm premature rupture of membranes.
  **Vitamins C and E: missing links in preventing preterm premature rupture of membranes? Am J Obstet Gynecol 2001 Jul;185(1):5-10.

• In a large-scale study examining the association of dietary beta-carotene, vitamin C, and vitamin E with peripheral arterial disease vitamin E intake was inversely associated with peripheral arterial disease in men.
  **Dietary antioxidants and peripheral arterial disease : the Rotterdam Study. Am J Epidemiol 2001 Jul 15;154(2):145-149

• A study was carried out of the sequel of oxidative insult to human erythrocytes induced by the water-soluble radical initiator AAPH and the effect of a mixed antioxidant containing alpha-tocopherol (Vitamin E), ascorbic acid (Vitamin C), beta-carotene (Vitamin A) and grape seed catechins and milk thistle derived silybin, on lipid peroxidation, degradation of membrane proteins and haemolysis. The antioxidant, suppressed lipid peroxidation and protected membrane proteins against degradation induced by peroxyl radicals, and effectively delayed AAPH induced haemolysis.
  **Oxidative insult to human red blood cells induced by free radical initiator AAPH and its inhibition by a commercial antioxidant mixture. Life Sci 2001 May 25;69(1):75-86

• Results of an epidemiological study suggest that in apparently healthy, community-dwelling very old subjects, base-line plasma concentration of vitamin E predicts the risk of future cardiovascular events. The subjects with vitamin E levels in the highest quartile had a risk of cardiovascular events one-sixth those with vitamin E levels in the lowest quartile.
  **Vitamin E and lipid peroxide plasma levels predict the risk of cardiovascular events in a group of healthy very old people. J Am Geriatr Soc 2001 May;49(5):533-537

• Animal studies reveal that the balance between pro-oxidants and anti-oxidants in the LDL particle (such as cholesteryl ester vs. vitamin E) determines the extent of LDL oxidation.
  **Macrophage foam cell formation during early atherogenesis is determined by the balance between pro-oxidants and anti-oxidants in arterial cells and blood lipoproteins. Antioxid Redox Signal 1999;1(4):585-594

Broccoli

• Cruciferous vegetables like broccoli contain high levels of vitamins that can act as antioxidants, compounds that may protect against several degenerative diseases.
  **Carotene, tocopherol, and ascorbate contents in subspecies of Brassica oleracea. J Agric Food Chem 1999 Apr;47(4):1576-81
• Broccoli extract had the greatest protective effect against N-nitrosamines of all vegetable extracts tested. N-nitrosamines are common environmental carcinogens.
  Protective Effect of Broccoli, Onion, Carrot, and Licorice Extracts against Cytotoxicity of N-Nitrosamines **Evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide Assay. J Agric Food Chem. 1998 Feb 16;46(2):585-589.
• Broccoli has a multitude of antimutagenic factors.
  **Modifying actions of solvent extracts from fruit and vegetable residues on 2-amino- 3- methylimidazo [4,5-f]quinoline (IQ) and 2-amino-3,4- dimethylimidazo [4,5-f]quinoxaline (MeIQx) induced mutagenesis in Salmonella typhimurium TA 98. Mutat Res 1995 Feb;341(4):303-18
• The induction of detoxication enzymes by sulforaphane may be a significant component of the anticarcinogenic action of broccoli.
  **A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2399-403.
• Among foods high in carotenoids, broccoli and spinach were most consistently associated with a lower risk of cataracts.
  **A prospective study of carotenoid intake and risk of cataract extraction in US men. Am J Clin Nutr 1999 Oct;70(4):517-24

• Indole-3-carbinol, a phytochemical abundantly present in broccoli, has the ability to alter estrogen metabolism, thereby preventing tumorigenesis and decreasing the formation of certain carcinogenic estrogen products in the human body.  In addition to these indirect effects resulting from altered estrogen metabolism, indole-3-carbinol has been shown to directly arrest the cell cycle of cancerous cells. In addition to its antitumor activity in animals, it has also been shown to be effective against HPV-mediated tumors in human patients.
  **Multifunctional aspects of the action of indole-3-carbinol as an antitumor agent. Ann N Y Acad Sci 1999;889:204-13

• Epidemiological studies have linked consumption of broccoli to a reduced risk of colon cancer in individuals with the glutathione S-transferase M1 (GSTM1) null genotype. Glutathione S-transferases are involved in excretion and elimination of isothiocyanates (ITCs), which are major constituents of broccoli and other cruciferous vegetables and have cancer chemopreventive potential, so it is speculated that ITCs may play a role in protection against human colon cancer. The authors carried out a bioassay which determined that sulforaphane (SFN) and phenethyl isothiocyanate (PEITC), major ITCs in broccoli, and their corresponding N:-acetylcysteine (NAC) conjugates, show chemopreventive activity towards azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. These findings provide important laboratory evidence for a potential role of SFN and PEITC in the protection against colon cancer.
  **Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate. Carcinogenesis 2000 Dec;21(12):2287-2291

• The broccoli constituent sulforaphane has previously been shown to protect rats against certain types of tumor growth. The effect is thought to be due, at least in part, to induction of phase II detoxifying enzymes. In this study, an initial laboratory experiment on rat liver cells demonstrated that sulforaphane is a potent inhibitor of the phase I enzyme cytochrome P450 isoenzyme 2E1 (CYP2E1), which is responsible for activation of several carcinogens, including dialkylnitrosamines.
  **CYP2E1-mediated mechanism of anti-genotoxicity of the broccoli constituent sulforaphane. Carcinogenesis 1996 Feb;17(2):277-82
• The data of this study suggest that regular consumption of broccoli reduces risk of death from coronary heart disease (CHD) in postmenopausal women. In this experimental group total flavonoid intake was associated with a decreased risk of CHD death after adjusting for age and energy intake. Decreased risk was seen in each category of intake compared with the lowest. Of the foods that contributed the most to flavonoid intake in the
  group studied, only broccoli was strongly associated with reduced risk of CHD death.
  **Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women. Am J Epidemiol 1999 May 15;149(10):943-9

• The authors of a review of eighty prior epidemiological studies on the association between consumption of brassica vegetables and cancer risk conclude that a high consumption of brassica vegetables, including broccoli, is associated with a decreased risk of cancer. The association appears to be most consistent for lung, stomach, colon and rectal cancer.
  **Brassica vegetables and cancer prevention. Epidemiology and mechanisms.  Adv Exp Med Biol 1999;472:159-68

• Disruption of plant structure during the preparation and chewing of broccoli and other Brassica vegetables containing the compound glucobrassicin produces several chemical products that are responsible for inhibiting the growth of cancerous cells. These include indole-3-carbinol (I3C), glucose, and thiocyanate ion.
  **Modification of carcinogen metabolism by indolylic autolysis products of Brassica oleraceae. Adv Exp Med Biol 1991;289:153-63

• Of nine fruit and vegetable extracts tested, broccoli extract exhibited the strongest protective effect and stimulation of cellular proliferation against the the N-nitrosamines NDMA, NPYR, NDBA, and NPIP. All are potent cytotoxic chemical carcinogens.
  **Protective Effect of Broccoli, Onion, Carrot, and Licorice Extracts against Cytotoxicity of N-Nitrosamines Evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide Assay. J Agric Food Chem. 1998 Feb 16;46(2):585-589.

• Sulforaphane was recently isolated from one variety of broccoli as the major and very potent inducer of phase 2 detoxication enzymes. Since phase 2 enzyme induction is often associated with reduced susceptibility of animals and their cells to the toxic and neoplastic effects of carcinogens and other electrophiles, it was important to establish whether sulforaphane could block chemical carcinogenesis. In this paper we report that sulforaphane and three synthetic analogues block the formation of mammary tumors in rats treated with single doses of 9,10-dimethyl-1,2-benzanthracene.
  **Anticarcinogenic Activities of Sulforaphane and Structurally Related Synthetic Norbornyl Isothiocyanates. Proceedings of the National Academy of Sciences, Vol 91, 3147-3150

• This study shows that sulforaphane, an isothiocyanate highly concentrated in broccoli, kills human colon carcinoma cells (HT29) during their exponentially growing phase. The authors observed that sulforaphane triggers the release of detoxifying enzymes that arrest the cell-growth cycle in a dose-dependent manner. The cancerous cells then self-destruct in an orderly process displaying the characteristic features of apoptosis, or cell suicide.
  **Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells.  Cancer Res 2000 Mar 1;60(5):1426-33.

• Indole-3-carbinol (I3C) is produced in the human body from naturally occurring glucosinolates contained in a wide variety of plant foods, including broccoli, whenever they are crushed or cooked. I3C and its derivative compounds are important because of their enzyme induction and suppression, mutagenic, carcinogenic and, particularly, antimutagenic and anticarcinogenic properties against a variety of classes of carcinogens. In a critical review of more than 170 papers, the authors conclude that I3C and related compounds have considerable potential as natural prophylactic anticancer agents against certain common cancers, especially inasmuch modern diets are increasingly deficient in these vegetable-derived substances.
  **The chemistry and pharmacology of indole-3-carbinol (indole-3-methanol) and 3-(methoxymethyl)indole. Curr Med Chem 1998 Dec;5(6):469-91

Carrot

• Epidemologic studies have shown a strong association between the consumption of carotenoid-rich vegetables such as carrots and reduced incidence of cancer. Carrots are a good source of beta-carotene.
  **Development and evaluation of a new method for the determination of the carotenoid content in selected vegetables by HPLC and HPLC-MS-MS. J Chromatogr Sci 2000 Oct;38(10):441-9
• Carrot extract has an antimutagenic effect against four n-nitrosamine compounds, NDMA, NPYR, NDBA, and NPIP. N-nitrosamines are common environmental carcinogens.
  **Antimutagenic effect of fruit and vegetable ethanolic extracts against N-nitrosamines evaluated by the Ames test. J Agric Food Chem 1999 Aug;47(8):3257-64
• Higher vegetable consumption, particularly of carrots, may significantly reduce the risk of lung cancer.
  **Prospective study of smoking, antioxidant intake, and lung cancer in middle-aged women (USA). Cancer Causes Control 1999 Oct;10(5):475-82
• In human subjects, carrot juice significantly inhibited formation of the carcinogenic compound N-nitrosoproline (NPRO) relative to a control group. The data demonstrate that carrot juice has greater ability to inhibit the formation of carcinogenic compounds than would be expected based solely on its Vitamin C content.
  **Influence of fruit and vegetable juices on the endogenous formation of N-nitrosoproline and N-nitrosothiazolidine-4-carboxylic acid in humans on controlled diets. Carcinogenesis 1992 Dec;13(12):2277-80
• Carrots are a major dietary source of lutein. Lutein intake is inversely associated with colon cancer in both men and women. Incorporating carrots into the diet may help reduce the risk of developing colon cancer.
  **Carotenoids and colon cancer. Am J Clin Nutr 2000 Feb;71(2):575-82

• Carrots exhibited significant protective effect and stimulation of cellular proliferation against the the N-nitrosamines NDMA, NPYR, NDBA, and NPIP. All are potent cytotoxic chemical carcinogens.
  **Protective Effect of Broccoli, Onion, Carrot, and Licorice Extracts against Cytotoxicity of N-Nitrosamines Evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide Assay. J Agric Food Chem. 1998 Feb 16;46(2):585-589.

• After two weeks of carrot juice consumption by 23 healthy male volunteers, alpha-carotene and beta-carotene concentrations increased 8.6- and 3.2-fold, respectively.
  **Plasma concentrations of carotenoids in healthy volunteers after interventionwith carotenoid-rich foods. Eur J Nutr 1999 Feb;38(1):35-44

• Anthocyanin, a deep-red colour pigment from carrot cell culture has been found to be a potent antioxidant compared to classical antioxidants such as butylated hydroxy anisole (BHA), butylated hydroxy toulene (BHT) and alpha tocopherol. This natural agent, in addition to imparting colour to the food, might prevent autooxidation of lipids as well as lipid peroxidation in biological systems.
  **Antioxidant effect of anthocyanin on enzymatic and non-enzymatic lipid peroxidation. Prostaglandins Leukot Essent Fatty Acids 1999 Jan;60(1):1-4

• Carrots exert a cancer-protective effect via a decrease in oxidative and other damage to DNA in humans. A human intervention study with vegetable products has been performed in twenty three healthy, non smoking males aged 27-40. The supplementation of the diet with tomato, carrot or spinach products resulted in a significant decrease in endogenous levels of strand breaks in lymphocyte DNA. Oxidative base damage was significantly reduced during the carrot juice intervention.
  **Consumption of vegetables reduces genetic damage in humans: first results of a human intervention trial with carotenoid-rich foods. Carcinogenesis 1997 Sep;18(9):1847-1850

• Results of the preceding study indicate that reduced genetic DNA damage in lymphocytes may be due to the enhancement of cytosolic GSTP1, and DNA-repair proteins by carrot juice. Enhancement of cytosolic proteins may be indicative of increased gene expression by carrot juice, some of which may be associated with protective activities.
  **Mechanisms by which vegetable consumption reduces genetic damage in humans. Cancer Epidemiol Biomarkers Prev 1998 Oct;7(10):891-899

• In habitual cigarette smokers, antioxidant vitamins, which can be feasibly provided from carrots, partly protected LDL from oxidation despite a diet rich in polyunsaturated fatty acids.
  **Dietary supplementation with orange and carrot juice in cigarette smokers lowers oxidation products in copper-oxidized low-density lipoproteins. J Am Diet Assoc 1995 Jun;95(6):671-675

• Even in the absence of smoking, reducing alcohol and saturated fat intake and increasing fruit and carrot consumption may have favorable effects on oral and pharyngeal cancer risk.
  **Risk factors for oral and pharyngeal cancer in never smokers. Oral Oncol 1999 Jul;35(4):375-378

• A Swedish study of dietary risk factors for lung cancer among never-smokers found evidence linking a diet rich in vegetables and non-citrus fruit with decreased lung cancer risk and suggests that among vegetables, carrot consumption is the most important component or marker for this effect.
  **Dietary factors and risk of lung cancer in never-smokers. Int J Cancer 1998 Nov 9;78(4):430-436

• A hospital-based case-control study of 94 men and women with malignant mesothelioma and 64 control patients without cancer was conducted to determine the odds associated with consumption of carotenoid-containing fruits and vegetables. Carrot consumption reduced the odds of malignant mesothelioma by a factor of five. These results provide some justification for the hypothesis that provitamin A or beta-carotene may decrease the risk of mesothelioma.
  **Dietary intake and the risk of malignant mesothelioma. Br J Cancer 1996 May;73(9):1122-1125

Cabbage

• The consumption of cruciferous vegetables (the Family of Cruciferae) including cabbage, broccoli and Brussels sprouts has been shown to have cancer chemopreventive effects in humans and experimental animals. Indole-3-carbinol (I3C), one component of cruciferous vegetables, has been shown to exert cancer chemopreventive influence in liver, colon, and mammary tissue when given before or concurrent with exposure to a carcinogen.
  **Post-initiation treatment of Indole-3-carbinol did not suppress N-methyl-N-nitrosourea induced mammary carcinogenesis in rats. Cancer Lett 2001 Aug 28;169(2):147-54
• In a study of the most common cruciferous vegetable subspecies, cabbage was found to contain a significant concentration alpha-carotene, beta-carotene, alpha-tocopherol, gamma-tocopherol, and ascorbate. Cruciferous vegetables contain high levels of vitamins that can act as antioxidants, compounds that may protect against several degenerative diseases.
  **Carotene, tocopherol, and ascorbate contents in subspecies of Brassica oleracea. J Agric Food Chem 1999 Apr;47(4):1576-81

• Indole-3-carbinol, a phytochemical abundantly present in cabbage, has the ability to alter estrogen metabolism, thereby preventing tumorigenesis and decreasing the formation of certain carcinogenic estrogen products in the human body.  In addition to these indirect effects resulting from altered estrogen metabolism, indole-3-carbinol has been shown to directly arrest the cell cycle of cancerous cells. In addition to its antitumor activity in animals, it has also been shown to be effective against HPV-mediated tumors in human patients.
  **Multifunctional aspects of the action of indole-3-carbinol as an antitumor agent. Ann N Y Acad Sci 1999;889:204-13

• Indole-3-carbinol, found in high concentration in cruciferous vegetables (i.e., cabbage, cauliflower, broccoli, rabe, brussels sprouts, kale, and bok choi), has been shown to reduce mammary cancer in rodent models.
  **Chemoprevention of breast cancer. Surg Clin North Am 1999 Oct;79(5):1207-21
• Consumption of vegetables, especially crucifers such as cabbage, reduces the risk of developing cancer. Eating vegetables accelerates the metabolic disposal of toxic substances from the body.
  **A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2399-403.

• The authors of a review of eighty prior epidemiological studies on the association between consumption of brassica vegetables and cancer risk conclude that a high consumption of brassica vegetables, including cabbage, is associated with a decreased risk of cancer. The association appears to be most consistent for lung, stomach, colon and rectal cancer.
  **Brassica vegetables and cancer prevention. Epidemiology and mechanisms. Adv Exp Med Biol 1999;472:159-68

• A study investigated risk factors for thyroid carcinomas and adenomas in Southwestern Germany confirmed the protective role of the consumption of cruciferous vegetables such as cabbage for both genders.
  **Association between malignant tumors of the thyroid gland and exposure to environmental protective and risk factors. Rev Environ Health 2000 Jul-Sep;15(3):337-58 

• Disruption of plant structure during the preparation and chewing of cabbage and other Brassica vegetables containing the compound glucobrassicin produces several chemical products that are responsible for inhibiting the growth of cancerous cells. These include indole-3-carbinol (I3C), glucose, and thiocyanate ion.
  **Modification of carcinogen metabolism by indolylic autolysis products of Brassica oleraceae. Adv Exp Med Biol 1991;289:153-63

• Cabbage is among the foods and herbs with the highest anticancer activity. Consuming a diet rich in plant foods will provide a milieu of phytochemicals, non-nutritive substances in plants that have been associated with protection from and/or treatment of conditions such as cardiovascular disease and cancer.
  **Phytochemicals: Health Protective Effects. Can J Diet Pract Res 1999;60(2):78-84

Lutein

• Regular consumption of vegetables like broccoli that are high in the carotenoid lutein is associated with a reduced risk of colon cancer. The inverse association between lutein intake and colon cancer was confirmed for both men and women.
  **Carotenoids and colon cancer. Am J Clin Nutr 2000 Feb;71(2):575-82

• A study assessed the protective effects of the oxygenated carotenoid lutein against early atherosclerosis.  Epidemiological, in vitro, and mouse model findings support the hypothesis that increased dietary intake of lutein is protective against the development of early atherosclerosis.
  **Dwyer JH, Navab M, Dwyer KM, Hassan K, Sun P, Shircore A, Hama-Levy S, Hough G, Wang X, Drake T, Merz CN, Fogelman AM. Circulation 2001 Jun 19;103(24):2922-2927

• Increased intake of lutein around the time of conception is associated with decreased risk of neural tube defects.
  **Periconceptional nutrient intake and risk for neural tube defect-affected pregnancies. Epidemiology 1999 Nov;10(6):711-6

• The authors evaluated the relationship between plasma levels of six carotenoids, alpha-tocopherol, and retinol, sampled before diagnosis, and later breast cancer risk. A significant trend of an inverse association between lutein and breast cancer risk was seen in premenopausal women from two combined population-based cohorts with only incident cases.
  **Carotenoids, alpha-tocopherols, and retinol in plasma and breast cancer risk in northern Sweden. Cancer Causes Control 2001 Aug;12(6):529-537

• In a study of carotenoid intake and breast cancer risk, there was an evident increase in risk for decreasing beta-carotene, lutein, alpha-carotene, and beta-cryptoxanthin. The risk of breast cancer doubled among subjects with blood levels of lutein in the lowest quartile as compared to those with the highest quartile. These observations offer evidence that a low intake of carotenoids, through poor diet and/or lack of vitamin supplementation, may be associated with increased risk of breast cancer and may have public health relevance for people with markedly low intakes.
  **Serum carotenoids and breast cancer. Am J Epidemiol 2001 Jun 15;153(12):1142-1147

• Macular pigmentation could be augmented by supplemental lutein in many patients with inherited retinal degeneration.
  **Macular pigment and lutein supplementation in retinitis pigmentosa and usher syndrome. Invest Ophthalmol Vis Sci 2001 Jul;42(8):1873-81
• A 2001 study confirms the inverse associations between lycopene, other carotenoids such as lutein, and prostate cancer.
  **Inverse associations between plasma lycopene and other carotenoids and prostate cancer. Cancer Epidemiol Biomarkers Prev 2001 Jul;10(7):749-56
• Epidemiological, in vitro, and mouse model findings support the hypothesis that increased dietary intake of lutein is protective against the development of early atherosclerosis.
  **Oxygenated carotenoid lutein and progression of early atherosclerosis: the Los Angeles atherosclerosis study. Circulation 2001 Jun 19;103(24):2922-7

• In a study of the association between dietary intake of carotenoids and the incidence of ovarian cancer, participants with the highest dietary intake of lutein/zeaxanthin had a 40% lower risk of ovarian cancer compared to those with the lowest intake.
  **A population-based case-control study of carotenoid and vitamin A intake and ovarian cancer (United States). Cancer Causes Control 2001 Jan;12(1):83-90

Bilberry

• Bilberry is among the nutrients and botanicals which may benefit cataract patients or help prevent cataracts.
  **Natural therapies for ocular disorders, part two: cataracts and glaucoma. Altern Med Rev 2001 Apr;6(2):141-66
• Bioflavinoids such as those found in fruits including bilberry have been found to improve the function of the blood brain barrier.
  **Effects of Toxic Metals on Learning Ability and Behavior. www.Talkinternational.com
• Bilberry contains between 14 and 142 mg/kg of the flavonol myricetin, a powerful antioxidant.
  **Content of the flavonols quercetin, myricetin, and kaempferol in 25 edible berries. J Agric Food Chem 1999 Jun;47(6):2274-9
• Components of the hexane/chloroform fraction of bilberry exhibit potential anticarcinogenic activity according to laboratory screening tests.
  **In vitro anticancer activity of fruit extracts from Vaccinium species. Planta Med 1996 Jun;62(3):212-6
• The aqueous extract of bilberry inactivated tick-borne encephalitis virus practically completely.
  **[Experimental phytotherapy of tick-borne encephalitis]. Vopr Virusol 1991 Jan-Feb;36(1):18-21

• Bilberries are high in anthocyanins, a class of phenolic compounds that have potent antioxidant effects.
  **Berry phenolics and their antioxidant activity. J Agric Food Chem 2001 Aug;49(8):4076-4082

• Anthocyanin pigments like those found in bilberry have powerful antimutagenic properties. Caffeic acid showed the strongest antimutagenicity of the constituent organic acids of the anthocyanin pigments, caffeic acid, ferulic acid, and p-hydroxybenzoic acid.
  **Antimutagenicity of deacylated anthocyanins in purple-fleshed sweetpotato. Biosci Biotechnol Biochem 2001 Jul;65(7):1652-1655

Lycopene

• Considerable evidence suggests that lycopene, a carotenoid found in high concentrations in a small set of plant foods, has significant antioxidant potential in vitro and may play a role in preventing cardiovascular disease in humans.
  **Lycopene and cardiovascular disease. Am J Clin Nutr 2000 Jun;71(6 Suppl):1691S-5S; discussion 1696S-7S
• Lycopene could play an important role in the recovery of the integrity of biological membranes of the liver after radiation injury.
  **Role of lycopene in recovery of radiation induced injury to mammalian cellular organelles. Pharmazie 2001 Mar;56(3):239-41
• A 2001 study confirms the inverse associations between lycopene, other carotenoids such as lutein, and prostate cancer.
  **Inverse associations between plasma lycopene and other carotenoids and prostate cancer. Cancer Epidemiol Biomarkers Prev 2001 Jul;10(7):749-56
• Tomatoes, high in lycopene, reduce the risk of prostate cancer.
  **An ecologic study of dietary links to prostate cancer. Altern Med Rev 1999 Jun;4(3):162-9
• The results of one recent study suggest a possible relationship between plasma lycopene level and breast cancer among African American women.
  **An Evaluation of Plasma Antioxidant Levels and the Risk of Breast Cancer: A Pilot Case Control Study. Breast J 2000 Nov;6(6):388-395
• The tomato carotenoid lycopene may have potential as a chemopreventive agent against carcinogenesis in the male lung.
  **Chemoprevention of lung cancer by lycopene. Biofactors 2000;13(1-4):95-102
• Lycopene was associated with significant reductions in risk of esophageal cancer.
  **Vegetables, fruits, related dietary antioxidants, and risk of squamous cell carcinoma of the esophagus: a case-control study in Uruguay. Nutr Cancer 2000;38(1):23-9.
• The carotenoid lycopene is the most efficient quencher of singlet molecular oxygen (1O2).  1O2 has been shown to be generated in biological systems and is capable of damaging proteins, lipids and DNA.
  **Carotenoids, tocopherols and thiols as biological singlet molecular oxygen quenchers. Biochem Soc Trans 1990 Dec;18(6):1054-6.
• Lycopene quenches singlet oxygen more than twice as effectively as beta-carotene.  Protection by beta-carotene and related compounds against oxygen-mediated cytotoxicity and genotoxicity: implications for carcinogenesis and anticarcinogenesis. Free Radic Biol Med 1992 Oct;13(4):407-33
  **Lycopene as the most efficient biological carotenoid singlet oxygen quencher. Arch. Biochem. Biophys. 274: 532-538.

Magnesium

• Magnesium affects many cellular functions, including transport of potassium and calcium ions, and modulates signal transduction, energy metabolism and cell proliferation. Magnesium supplementation may play an important role in management of alcoholism, eclampsia, hypertension, atherosclerosis, cardiac diseases, diabetes, and asthma.
  **Magnesium. An update on physiological, clinical and analytical aspects. Clin Chim Acta 2000 Apr;294(1-2):1-26
• Increased intake of magnesium around the time of conception is associated with decreased risk of neural tube defects.
  **Periconceptional nutrient intake and risk for neural tube defect-affected pregnancies. Epidemiology 1999 Nov;10(6):711-6
• A high-magnesium diet may help to prevent or postpone the onset of type 2 diabetes. High-magnesium diets have preventive activity in certain rodent models of diabetes; conversely, magnesium depletion provokes insulin resistance.
  **Toward practical prevention of type 2 diabetes. Med Hypotheses 2000 May;54(5):786-93
• Habitual intake of foods rich in potassium and magnesium is associated with reduced intensity and cost of medication and with preservation of blood pressure control in elderly people with high blood pressure.
  **Eating habits and intensity of medication in elderly hypertensive outpatients. Hypertens Res 2000 May;23(3):195-200
• An adequate intake of magnesium and potassium is essential for preventing osteoporosis. The rate of bone loss in the elderly can be reduced and the peak bone mass in the young can possibly be increased by dietary manipulation, thereby reducing the risk of fracture.
  **Nutritional factors in osteoporosis. Int J Clin Pract 1999 Oct-Nov;53(7):540-8
• Magnesium supplementation has a potential role in management of coronary artery disease.
  **Low intracellular magnesium levels promote platelet-dependent thrombosis in patients with coronary artery disease.  Am Heart J 2000 Aug;140(2):212-8
• Magnesium is one of a number of nutrients that reduce blood pressure among adolescents at risk for hypertension.
  **Arch Pediatr Adolesc Med 2000 Sep;154(9):918-22. Dietary nutrients and blood pressure in urban minority adolescents at risk for hypertension.

Astaxanthin

• Astaxanthin is about 2-fold more effective than beta-carotene in inhibiting production of lipid peroxides. The efficient antioxidant activity of astaxanthin is suggested to be due to the unique structure of the terminal ring moiety, which traps radicals both at the phospholipid membrane surface and in the membrane.
  **Efficient radical trapping at the surface and inside the phospholipid membraneis responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. Biochim Biophys Acta 2001 Jun 6;1512(2):251-258

• Astaxanthin, a carotenoid without vitamin A activity, enhances human immune function by increasing immunoglobulin production.
  Effect of carotenoids on in vitro immunoglobulin production by human peripheral blood mononuclear cells: astaxanthin, a carotenoid without vitamin A activity, enhances in vitro immunoglobulin production in response to a T-dependent stimulant and antigen. Nutr Cancer 1995;23(2):171-83

• Astaxanthin may exert antitumor activity through the enhancement of immune responses. In this study, researchers determined the effects of dietary astaxanthin on tumor growth and tumor immunity against transplantable methylcholanthrene-induced fibrosarcoma (Meth-A tumor) cells. The results indicate that dietary astaxanthin suppressed Meth-A tumor cell growth and stimulated immunity against Meth-A tumor antigen.
  **Antitumor activity of astaxanthin and its mode of action. Nutr Cancer 2000;36(1):59-65

• Astaxanthin is an efficient quencher of singlet molecular oxygen (1O2).
  **Carotenoids, tocopherols and thiols as biological singlet molecular oxygen quenchers. Biochem Soc Trans 1990 Dec;18(6):1054-6.
• As a scavenger of hydroxyl radicals, astaxanthin is more effective than beta-carotene.
  **Protection by beta-carotene and related compounds against oxygen-mediated cytotoxicity and genotoxicity: implications for carcinogenesis and anticarcinogenesis. Free Radic Biol Med 1992 Oct;13(4):407-33

• Consumption of astaxanthin inhibits LDL oxidation and therefore may contribute to the prevention of atherosclerosis.
  **Inhibition of low-density lipoprotein oxidation by astaxanthin. J Atheroscler Thromb 2000;7(4):216-222

• In animal experiments astaxanthin protected against liver damage induced by carbon tetrachloride by inhibiting lipid peroxidation and stimulating the cellular antioxidant system.
  **Effect of astaxanthin on the hepatotoxicity, lipid peroxidation and antioxidative enzymes in the liver of CCl4-treated rats. Methods Find Exp Clin Pharmacol 2001 Mar;23(2):79-84

• Helicobacter pylori infection in humans is associated with chronic type B gastritis, peptic ulcer disease, and gastric carcinoma. In this study mice inoculated with H. pylori and treated with astaxanthin-rich algal meal showed significantly lower colonization levels and lower inflammation scores than those of untreated or control-meal-treated animals at 1 day and 10 days after the cessation of treatment. Astaxanthin-rich algal meal showed an inhibitory effect on H. pylori growth in vitro. In conclusion, antioxidants may be a new strategy for treating H. pylori infection in humans.
  **Astaxanthin-rich algal meal and vitamin C inhibit Helicobacter pylori infection in BALB/cA mice. Antimicrob Agents Chemother 2000 Sep;44(9):2452-2457

Selenium

• The lens and retina of the human eye may suffer oxidative damage. Selenium has an anti-oxidant role.
  **Nutrition supplements and the eye. Eye 1998;12 ( Pt 1):127-33

• Selenium deficiency is associated with a nearly threefold higher likelihood of genital mucosal shedding of HIV-1—infected cells, suggesting that deficiency may increase the infectiousness of women with HIV-1. Nutritional interventions to prevent HIV-1 transmission warrant investigation.
  **Selenium deficiency is associated with shedding of HIV-1--infected cells in the female genital tract. J Acquir Immune Defic Syndr 2001 Apr 1;26(4):360-364

• Pathophysiological mechanisms of cataract formation include deficient glutathione levels contributing to a faulty antioxidant defense system within the lens of the eye. Nutrients to increase glutathione levels and activity include lipoic acid, vitamins E and C, and selenium.
  **Natural therapies for ocular disorders, part two: cataracts and glaucoma. Altern Med Rev 2001 Apr;6(2):141-66
• Supplementation with antioxidants such as alpha-tocopherol, N-acetyl cysteine, ascorbic acid, beta-carotene, and selenium can offer an achievable and inexpensive adjunct therapy to help inhibit the development of retinopathy in diabetes.
  **Abnormalities of retinal metabolism in diabetes and experimental galactosemia: vii. effect of long-term administration of antioxidants on the development of retinopathy. Diabetes 2001 Aug;50(8):1938-42
• Selective antioxidants including selenium can protect against methamphetamine-induced neurotoxicity. These antioxidants may have therapeutic potential in the treatment of psychostimulant addictions.
  **Methamphetamine-induced dopaminergic neurotoxicity: role of peroxynitrite and neuroprotective role of antioxidants and peroxynitrite decomposition catalysts. Ann N Y Acad Sci 2001 Jun;939:366-80

• Tablets containing selenium and tocopheryl succinate were given to fifty patients with low blood levels of glutathione-peroxidase (GSH-Px) suffering from various skin diseases including psoriasis, eczema, atopic dermatitis, vasculitis, mycosis fungoides and dermatitis herpetiformis. GSH-Px levels increased slowly within 6-8 weeks of treatment.
  Blood glutathione-peroxidase levels in skin diseases: effect of selenium and vitamin E treatment. Acta Derm Venereol 1982;62(3):211-4

• A balanced intake of selenium and Vitamin E is essential for proper regulation of the antioxidant staus of both the brain and the liver.
  **A comparative study on effect of dietary selenium and vitamin E on some antioxidant enzyme activities of liver and brain tissues. Biol Trace Elem Res 2001 Aug;81(2):141-152

• The dietary antioxidant Vitamins C, E, beta-carotene and the mineral selenium inhibit the frequency of mutations induced by treatment of rats with 7,12-dimethylbenz[a]anthracene (DMBA), a mammary carcinogen and bleomycin (BLM), an anti-tumor agent that can damage DNA by free radical mechanisms.
  **Influence of dietary antioxidants on the mutagenicity of 7,12-dimethylbenz. Mutat Res 2001 Sep 1;480-481(1-2):163-170

• Glutathione peroxidase (GPX)1 mRNA in rat liver falls dramatically during selenium deficiency to levels that are approx. 10% of selenium-adequate levels. Translational efficiency of GPX1 mRNA increases 20-fold with selenium supplementation.
  **Selenium regulation of transcript abundance and translational efficiency of glutathione peroxidase-1 and -4 in rat liver. Biochem J 2001 Aug 1;357( Pt 3):851-858

• Selenium and Vitamin E (tocopheryl succinate): Tablets containing selenium and tocopheryl succinate were given to fifty patients with low blood levels of glutathione-peroxidase (GSH-Px) suffering from various skin diseases including psoriasis, eczema, atopic dermatitis, vasculitis, mycosis fungoides and dermatitis herpetiformis. GSH-Px levels increased slowly within 6-8 weeks of treatment.
  **Blood glutathione-peroxidase levels in skin diseases: effect of selenium and vitamin E treatment. Acta Derm Venereol 1982;62(3):211-4

Glutathione

• A sufficient supply of glutathione is necessary as the substrate for enzymatic reactions of hydrogen peroxide or lipid hydroperoxide catabolism, as well as for detoxication of xenobiotics.
  Alternative nutrition and glutathione levels.
• In laboratory tests, glutathione (reduced form), showed superoxide dismutase (SOD)-like activity, indicating that it is a natural antioxidant.
  Measurement of superoxide dismutase-like activity of natural antioxidants. Biosci Biotechnol Biochem 1995 May;59(5):822-6
• An animal study demonstrates that dietary glutathione (GSH) supplementation can increase myocardial GSH content and antioxidant defense capacity, thereby protecting the intact heart against oxidative damage and functional retardation caused by ischemia-reperfusion.
  Glutathione supplementation and training increases myocardial resistance to ischemia-reperfusion in vivo. Am J Physiol Heart Circ Physiol 2001 Aug;281(2):H679-88
• Glutathione, a natural antioxidant, may be important in blood pressure and glucose homeostasis, consistent with the involvement of free radicals in both essential hypertension and diabetes mellitus.
  Effects of vitamin E and glutathione on glucose metabolism: role of magnesium. Hypertension 1999 Oct;34(4 Pt 2):1002-6
• Dietary supplementation with antioxidant vitamins has been shown to be beneficial in combating oxidative stress without enhancing performance while exogenous glutathione was found to influence the endurance capacity of athletes. Such studies demonstrate the critical role played by glutathione and suggest that intervention trials should include a mixture of antioxidants rather than a single antioxidant.
  Exercise, depletion of antioxidants and antioxidant manipulation. Cell Biochem Funct 1998 Dec;16(4):269-75
• Study of glutathione-deficient animals clearly indicates the central importance of having adequate tissue glutathione to protect against exercise-induced oxidative stress.
  Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr 2000 Aug;72(2 Suppl):653S-69S

• Animal studies reveal that the balance between pro-oxidants and anti-oxidants in arterial wall macrophages (such as NADPH oxidase vs. glutathione), determines the extent of LDL oxidation.
  **Macrophage foam cell formation during early atherogenesis is determined by the balance between pro-oxidants and anti-oxidants in arterial cells and blood lipoproteins. Antioxid Redox Signal 1999;1(4):585-594

• In an animal study, a preparation containing both licorice root powder and beta-carotene markedly increased antioxidant activity of the liver.
  **Antioxidant activity of parapharmaceutics containing natural inhibitors of free radical processes. Bull Exp Biol Med 2000 Jul;130(7):658-660

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