Antioxidants: What they do, how much to take

Comments from a Dec, 2004 nutrition international research conference on free radicals:

  SESSION 4: CLINICAL ASPECTS OF ANTIOXIDANT USAGE

" in 2002, 79% of consumers were aware of the association between calcium and osteoporosis; 54% for antioxidants and cancer; and 35% for soy protein and heart disease...many consumers do not seem convinced that antioxidants are as great a health benefit as reported in the media. ..Factors for health message effectiveness include the seriousness of the disease expressed in the claim (e.g., cancer is more serious than osteoporosis), the knowledge of the component (e.g., fruits and vegetables have many benefits), the association with supplements (e.g., consumers do not know what foods contain vitamin E), and the availability of the component (e.g., calcium is perceived to be in many foods; therefore, supplements are not as necessary).

It has been firmly established that antioxidants trap the free radicals responsible for the chain reactions which damage cells. By increasing the level of antioxidants, one decreases the risk for free radical damage and the 60 or more diseases associated with free radical damage. A wonderful article in May of 2005 describes the wonderful benefits of vitamin E and C, carotenoids, polyphenols, and other micronutritients (J. Nutr. 135:969-972). Of particular importance is the critical role of vitamins C and E. These two key antioxidants are being studied in many major clinical trials. Only when these two safe antioxidants are exhausted do the other antioxidants, which are needed only in catalytic quantities and are unsafe at higher levels, play a role. Clinical trials involving these other antioxidant substances have been discontinued because these other antioxidants, such as selenium and b-carotene, are dangerous to take in supplement form and increase the risk of cancer for many people.

Below is a lengthy list of citations supporting the value of antioxidants. The first by Losonczy convinced me of the value of vitamin C and E supplements.

1. Losonczy, K. G., Harris, T.B., and Havlik, R. J. "Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly", Am. J. Clin. Nutr. 64:190-6 (1996)

Study of 11,000 people over 66 for 3 years:

Relative risk of death, heart disease, and cancer in older people using supplements

2. "The oxidation of low-density lipoproteins (LDLs) is now commonly implicated as an important early event in atherogenesis. The resulting interest in LDL antioxidation has focused on alpha- tocopherol...We review...how the vitamin's antioxidant activity is enhanced or even dependent on the presence of suitable reducing species [especially vitamin C]". "alpha-tocopherol itself does not act as a chain-breaking antioxidant but rather facilitates the transfer of radical reactions from the aqueous phase into LDL" [Table 1 shows composition of LDL (molecules/LDL particle), including alpha-(6-12) and gamma-(0.5) tocopherol, ubiquinol-1(0.5-0.8), lycopene(0.2-0.7), and beta- carotene(0.1-0.4). All of these facilitate radical trapping, and any reduces free radical damage.] Thomas, S.R., Neuzil, J., Mohr, D. and Stocker, R., "Coantioxidants make alpha-tocopherol an efficient antioxidant for low-density lipoprotein", Am. J. Clin. Nutr. 62: 1357S-64S (1995)

3. "Uptake of oxidatively modified low-density lipoprotein (LDL) by cells in the arterial wall is believed to be an important early event in the development of atherosclerosis. Because vitamin E is the major antioxidant present in human lipoproteins, it has received much attention as a suppressor of LDL lipid oxidation and as an epidemiological marker for ischaemic heart disease...reagents which reduce the alpha-tocopherol radical (i.e. vitamin C and ubiquinol-10) strongly inhibit lipid peroxidation in vitamin E-containing LDL." Bowry, VW, Ingold, KU, and Stocker, R, "Vitamin E in human low-density lipoprotein", Biochem J 288: 341-44 (1992)

4. "ascorbate is an extremely effective antioxidant for LDL containing alpha- tocopherol...alpha-tocopherol in LDL can be regenerated from its radical by ascorbate; in the absence of ascorbate and coenzyme Q10 (ubiquinol-10), the alpha-tocopherol in LDL acts as a chain-transfer agent rather than as a radical trap"-Ingold, KU, Bowry, VW, Stocker, R, and Walling, C, "Autoxidation of lipids and antioxidantion by alpha-tocopherol and ubiquinol in homogeneous solution and in aqueous dispersions of lipids: Unrecognized consequences of lipid particle size as exemplified by oxidation of human low density lipoprotein", PNAS USA 90: 45-49 (1993)

5. [especially important because it shows that vitamins C and E are the key ones in human plasma, not strange ones marketed by many companies like pycnogenol, ginseng, etc.] "It is shown that contributions from urate (35-65%), plasma proteins (10-50%), ascorbate (0- 24%) and vitamin E (5-10%) to Total Radical Trapping [ability] account for all of the peroxyl radical-trapping antioxidant activity in the majority of the samples [of six freshly prepared and 45 frozen human plasma samples]... The modes of action of all of these plasma antioxidants and possible interactions between them are discussed, with particular emphasis on the abilities of the water-soluble antioxidants to regenerate or spare the only lipid-soluble antioxidant, vitamin E."-Wayner, DD, Burton, GW, Ingold, KU, Barclay, LRC, and Locke, SJ, "The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma", Biochim. Biophys Acta 924: 408-19 (1987)

6. Prieme, H. et al, "No effect of supplementation with vitamin E, ascorbic acid, or coenzyme Q10 on oxidative damage estimated by 8-oxo-7,8-dihydro-2'-deoxyguanosine excretion in smokers", Am. J. Clin. Nutr. 65: 503-7 (1997)

Another example of evidence opposed to supplementation. Note that group 1A, the only one to receive both vitamin C and E, the only group where a positive effect is expected based on reference 157 above, is excluded from the data analysis.

7. Frei, Balz, "Natural Antioxidants in Human Health and Disease", San Diego, Academic Press, 1994.

Best recent compendium of many papers by hundreds of authors on the overwhelming evidence favoring role of vitamins C and E in protecting the nervous system, immune system, vision, circulatory system, etc. from free radicals.

8. Stahelin, H.B., K. F. Gey, M. Eichholzer, E. Ludin, F. Bernasconi, J. Thurneysen, and G. Brubacher, "Plasma antioxidant vitamins and subsequent cancer mortality in the 12-year follow up of the prospective Basel Study", Am. J. Epidem. 133:766-75 (1991)

2,974 men. "low plasma levels of antioxidant vitamins are associated with an increased risk of subsequent cancer mortality."

9. Orr, T., "Regulatory Confusion Stymies Emerging New Health Market", Gen. Eng. News 13: 1 (1993)

"Case-control studies have shown site-protective effects against cancer of diets heavy in vitamin C, with the highest efficacy for the esophageal, oral and stomach sites, without any evidence of harmful effects." "Studies embracing over 100,000 participants who were followed as long as eight years...showed a 35% lower incidence of cardiovascular 'events' in those receiving supplements of the vitamin [E]. In addition, the vitamin shows no adverse effects at high oral doses." "Based on these studies, market analysts have calculated that more than $8.7 billion in health care cost savings could be realized each year by nationwide use of this vitamin [E]"

10. Harman, D., "Role of Antioxidant Nutrients in Aging: Overview", AGE 18:51-62 (1995)

"The beneficial effects of antioxidant nutrients are now supported by many studies, including those that have increased life span and lowered disease incidence."

11. Sies, H., and Krinsky, J.I., "The Present Status of Antioxidant Vitamins and b-carotene", Am. J. Clin. Nutr. 62(suppl): 1299S-1300S (1995)

Introduction to The Second International Conference on Antioxidant Vitamins and b-Carotene in Disease Prevention, one of the best and most recent symposia including 34 papers on the disease prevention ability of vitamins C and E, and aspirin, and the highly questionable value and possible dangers of b-carotene and multivitamins.

12. Byers, T. and Guerrero, N. , "Epidemiological evidence for vitamin C and vitamin E in cancer prevention", Am J Clin Nutr 62(suppl): 1385S-92S (1995)

Comparison of nearly 100 clinical trials of vitamins C and E in diet and supplements. Especially relevant is figure 7, which compares 20 cancer clinical trials of C and E supplements, showing reduction of risk in 18 of 20 trials of colon, oral, lung, breast, and prostate cancer.

13. Hennekens, C. H., Gaziano, J.M, Manson, J.E., and Buring, J.E.,"Antioxidant vitamin-cardiovascular disease hypothesis is still promising, but still unproven", Am J Clin Nutr 62(suppl): 1377S-80S (1995)

"Epidemiological studies have provided support for the hypothesis that people who consume high amounts of antioxidants through diet or supplements...tend to have lower risks of cardiovascular disease." The results of seven major clinical trails in the U.S., Canada, England, and Europe over the next several years should provide a reliable answer.

14. Packer, L., "Vitamin E Is Nature's Master Antioxidant", Sci. Amer., pg 54 (March/April 1994)

Explains function of vitamin E. Confirms that vitamin E is the key antioxidant in lipids, which is regenerated by vitamin C, the primary water soluble antioxidant. Thus, Vitamins C and E are the critical ones to prevent free-radical oxidation.

15. Williams, L.R., "Oxidative Stress, Neurodegeneration, and Neurotrophic Therapy", AGE 23rd Annual Meeting, pg. 16 (1993)

"The brain is particularly vulnerable to oxidative damage, and age-related neurodegeneration may be caused by the temporal accumulation of oxidative injuries....These susceptible neurons might be protected from death by boosting the brain's ability to deal with oxidative stress. Such protection could be provided by treatment of patients with...antioxidant drugs..."

16. Meydani, M., "Overview: Nutritional Intervention In Aging", AGE 23rd Annual Meeting, pg. 5 (1993)

Vitamin E and Calcium deficiencies are found in the majority of the elderly in the US. There is significant evidence on the benefit of vitamins C and E for improved cardiovascular health, of vitamin E for improved immune function, of vitamin C for maintaining good vision. Cataracts are 4-11x more common in those lacking vitamin C supplementation.

17. Buring, J.E., Gaziano, M. and Hennekens, C.H., "Antioxidant Supplementation On Aging And Related Diseases", AGE 23rd Annual Meeting, pg. 5 (1993)

Antioxidants prevent cholesterol oxidation. In a study of 87,000 nurses, vitamin E lowered risk for heart attack by 34%, vitamin C by 20%, and in combination by 46%. For 100 mg aspirin every other day, there is an immediate reduction in risk for heart attacks. 600 IU of vitamin E was recommended, with natural vitamin E showing better uptake than synthetic vitamin E.

18. Blot WJ; Li JY; Taylor PR; Guo W; Dawsey S; Wang GQ; Yang CS; Zheng SF; Gail M; Li GY; et al , "Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population", J Natl Cancer Inst 85: 1483-92 (1993)

"21% less gastric cancer was found in the supplemented group"

19. Robertson, J. M., Donner, A.P., and Trevithick, J.R., "A Possible Role For Vitamins C And E. In Cataract Prevention", Am. J. Clin. Nutr. 53: 346S-51S (1991)

In a study of 175 people and matched controls, "the latter group used significantly more supplementary vitamins C and E, and had a reduction in the risk of cataracts of 50%"

20. Block, G., "The Data Support a Role for Antioxidants in Reducing Cancer Risk", Nutr. Rev. 50: 207-213 (1992)

"Ascorbic Acid has been shown to protect human sperm from endogenous oxidative DNA damage. Thus deficiency may increase the risk of childhood genetic defects and childhood cancer." [So adults taking vitamin C are less likely to have children with birth defects or cancer] "[The FDA has not endorsed vitamins C and E even though they acknowledge their effectiveness] because 'it is not clear ...what dosage of vitamin C is necessary to achieve biologically effective inhibition...; similar comments were made for vitamin E... Of stomach or esophageal cancer studies, 15 of 15 that calculated vitamin C intake found statistically significant protection. Indeed for a wide array of cancers (lung, larynx, oral, esophagus, colon, rectum, pancreas, stomach, cervix, bladder", 33 of 46 studies that calculated vitamin C intake found statistically significant reduced risk with high dietary intake, and all were in the protective direction. .. Of all the studies at these cancer sites that have specifically examined vitamins C, E, or b-carotene, approximately 120 of 130 have found statistically significant reduced risk."

21. Buiatti, E., Palli, D. Decarli, A., Amarori, D. and Blot, W.J., "A Case-control Study of Gastric Cancer and Diet in Italy: II. Association With Nutrients", Intl. J. Cancer 45:896-901 (1990)

"Ascorbic acid showed the strongest geographic gradient, with the highest consumption for low risk areas [for gastric cancer]. The findings suggest that the protective effects we previously reported...may be linked to vitamins C and E..."

22. Cutler, R. G. , "Antioxidants and Aging", Am. J. Clin. Nutr. 53:373S-9S (1991)

"These results suggest a role for oxyradicals in causing aging and that the antioxidant status of an individual could be important in determining frequency of age-dependent diseases and duration of general health maintenance."

23. Niki. E., Saito, T., Kawakami, A., and Kamiya, Y., "Inhibition of oxidation of methyl-linoleate in solution by vitamin E and vitamin C", J. Biol. Chem. 259: 4177-4182 (1984)

Antioxidants reduce age-associated cell damage. "vitamin E trapped the peroxy radical and the resulting... radical reacted with vitamin C to regenerate vitamin E."