X-Message-Number: 3710
From:  (David Stodolsky)
Subject: CRYONICS: Antioxidants
Date: Fri, 20 Jan 95 16:13:31 +0100 (CET)

Forward of article <> () by Billi Goldberg 
From: Billi Goldberg <>
Newsgroups: sci.med.aids
Subject: Antioxidants
Date: 12 Jan 1995 10:09:05 -0600

Another point of view concerning antioxidants.


Herbert V. The antioxidant supplement myth. American Journal of Clinical 
Nutrition, 1994 Aug, 60(2):157-8.

The nutrition buzzword for 1994 is "antioxidant." Every  
supplement so labeled is seen as having only an upside and no  
downside. This is a myth. No supplement is a pure antioxidant. 

At the November 1-3, 1993 Food and Drug Administration (FDA)  
Conference on Antioxidant Vitamins in Cancer and Cardiovascular  
Disease (1), there was essentially unanimous agreement that  
vitamins C, E, and Beta-carotene are mischaracterized by  
describing them solely as "antioxidants" (fighters against harmful  
free radicals). They in fact are redox agents, antioxidant in some  
circumstances (often so in the physiologic quantities found in  
food), and prooxidant (producing billions of harmful free radicals)  
in other circumstances (often so in the pharmacologic quantities  
found in supplements). 

Excessive antioxidant action can adversely affect key physiological  
processes (1). Pharmacologic amounts of "antioxidant" vitamins  
have chemical actions that are neither antioxidant nor prooxidant  
(1, 2). For example, protection by pharmacologic amounts of  
vitamin E against heart attacks may have more to do with the  
prohemorrhagic action of megadoses of vitamin E and, being  
prohemorrhagic, in some circumstances vitamin E may promote  
excessive bleeding (2-4). 

Large doses of vitamin E enhance immune activity and thus may  
promote progression of immune and autoimmune diseases (e.g.,  
asthma, food allergy, diabetes, rheumatoid arthritis, multiple  
sclerosis, and lupus) (5). Large doses of vitamin C can promote  
kidney stones (2). 

Vitamin C is especially dangerous in the presence of high body  
iron stores, which make vitamin C violently prooxidant (1, 6, 7).  
For genetic reasons (7), more than 10% of American whites and  
perhaps as many as 30% of American blacks have high body iron. 

For consumer protection, every advertisement and label for vitamin  
C and/or iron supplements should warn: Do not take this product  
until your blood iron status has been determined. Six percent of  
Americans are in negative iron balance, and this product may help  
them. Twelve percent of Americans are in positive iron balance  
and this product may hurt them. 

Iron status is determined by measuring serum ferritin and, if it is  
high, also measuring serum iron. Alternatively, it is measured by  
determining percent saturation of the serum iron-binding capacity.  
Measuring serum ferritin alone is inadequate, because each  
molecule of serum ferritin may have anywhere from no iron to  
4500 atoms of iron on it (6). 

In 1963, we demonstrated in a patient with scurvy and folic acid  
deficiency that 1 gram of vitamin C mobilized into his blood  
enough iron from high body stores to saturate his iron-binding  
capacity (8). In iron overload due to transfusion therapy of patients  
with thalassemia or sickle cell disease, vitamin C can mobilize  
enough iron from body stores to overwhelm the iron-binding  
capacity of iron-binding proteins, with the resultant free iron  
producing death within minutes to hours from iron-induced cardiac  
failure (9). 

The 1993 report of a group of 29 584 vegetarian Chinese with a  
high frequency of esophageal cancer (10) has been represented as  
evidence that "antioxidant" supplements protect against cancer.  
This is not so. The study showed three things, none of them new:  
1) their vegetarianism did not protect the Chinese against cancer,  
2) nutrient deficiencies promote the development of some cancers,  
and 3) correcting those nutrient deficiencies reduces the frequency  
of those cancers. 

It has been known for many years that nutrient deficiencies  
promote cancers. The Plummer-Vinson syndrome, caused by iron  
deficiency, has been known for more than half a century to  
promote the development of esophageal cancer (10). The Chinese  
study subjects were deficient (i.e., their intakes were below  
minimal daily vitamin requirements to sustain normal metabolism)  
in so-called "antioxidant" vitamins A, Beta-carotene, and E.  
Supplements, containing Beta-carotene and vitamin E, by raising  
intakes above the minimum daily requirement, eliminated the  
deficiencies that promoted the cancers, thereby reducing the  
frequency of those cancers. Interestingly, vitamin C supplements  
were worthless against cancer (11), just as they (and Beta-carotene)  
proved worthless against heart disease (12, 13). 

Our own group (14) reported that in the area in China with the  
highest frequency of folic acid deficiency (caused by cooking the  
nutrients out of food), vitamin B-12 deficiency (caused by  
vegetarianism), and esophageal carcinoma, we could reverse  
toward normal precancerous esophageal dysplasia, by either  
improving the diets (by less prolonged cooking of food plus adding  
a few ounces of animal protein three to four times a week), or  
keeping the bad diet and administering supplements of vitamin B- 
12 and folic acid. Those esophageal dysplasia cells not yet  
committed to be cancer cells reversed to normal; the committed  
cells did not. 

We recently reported that in the presence of iron, not only does  
vitamin C appear to be worthless against cancer (15), but it  
increased lipoxidation of relatively harmless low-density- 
lipoprotein (LDL) cholesterol to coronary-artery-damaging  
oxidized LDL cholesterol (16). Vitamin C is so potent a redox  
agent in the presence of iron that vitamin E researchers use a  
vitamin C iron mixture to inactivate vitamin E in the test tube (17). 

Strong support for this position is provided by a randomized.  
double-blind. placebo-controlled primary-prevention trial  
comparing daily supplementation with alpha-tocopherol, Beta- 
carotene, both, or placebo. In 29133 male smokers in Finland (18),  
neither vitamin prevented lung cancer. In fact, lung cancer rates  
were 18 higher with Beta-carotene than with placebo, and there  
were more heart disease deaths. As we predicted because of the  
prohemorrhagic action of vitamin E supplements, men taking  
vitamin E had more hemorrhagic strokes. They did have less  
prostate cancer. Total (all cause) mortality was 8% higher among  
those who took Beta-carotene than among those taking placebo. 

A study showing that B-carotene supplements produced 18% more  
lung cancer than a placebo in smokers (18) was to be expected.  
"Antioxidant" vitamin supplements are unbalanced biochemistry,  
i.e., only in the reduced form, which can drive free radical  
generation by catalytic iron (16, 19). A second reason vitamin C  
supplements would be expected to increase lung cancer and  
mortality in smokers is that vitamin C supplements drive nicotine  
out of the blood into the urine (19), causing smokers to reach for  
that next cigarette (more carcinogens) that much faster to sustain  
their nicotine "high." We are now investigating whether beta- 
carotene supplements also drive nicotine into the urine. Vitamin C  
supplements can double cardiac risk (16, 19). 

American diets average 120% of the recommended dietary  
allowances (RDAs) for vitamin A, beta-carotene, and vitamin C  
(2). Dietary vitamin E deficiency has never been reported in the  
United States (2). Thus, has 1994 research confirmed the wisdom  
of 10th Recommended Dietary Allowance Committee authors  
Olson and Hodges (20,21) in lowering the recommended dietary  
allowance (RDA) for vitamins A and C, and rejected that of the  
Subcommittee editors (22) to not only have a high vitamin C RDA  
of 60 mg, but to raise it to 100 mg for smokers. 

The answer to the question, "If I drink orange juice for vitamin C,  
why not take a vitamin C pill for the same effect?" is that the effect 
is entirely different. "Antioxidant" vitamins as naturally present in  
food are balanced biochemistry, i.e., part of a mixture of redox  
agents half in oxidized form and half in reduced form. Every  
supplement pill, including those containing vitamin C, is  
unbalanced biochemistry. 

Insun Kim and her coworkers at the Centers for Disease Control  
and Prevention reported in 1993 (23) that supplements were  
worthless to increase longevity. Supplements help some, harm  
some, and do nothing for most, so the bottom line is a wash. For  
truth in advertising, all supplements should be labeled:  
"Supplements can help some people, harm others, and have no  
effect on most (2)." Apparently not comprehending the meaning of  
all the adverse facts, including those from us (19), presented at the  
FDA conference (1) which she attended, Bonnie Liebman of the  
Center for Science in the Public Interest continued to promote  
"antioxidant" beta-carotene and vitamin E supplements in Nutrition 
Action Healthletter, finally retracting (24) only after publication of 
the New England Journal study (18).  


1. Food and Drug Administration. November 1-3, 1993, FDA  
Conference on Antioxidant Vitamins and Cancer and Cardiovascular 
disease. Washington D.C. Office of Special  Nutritionals. 1993 

2. Herbert V. Subak-Sharpe, G. Hammock DA. eds.,. The Mount  
Sinai School of  Medicine Complete Book of Nutrition. New York: St 
Martin's Press, 1990. 

3. Horwitt M. In reference 1 above. 

4. Marshall C. Vitamins and minerals: help or harm? Philadelphia:  
George F Stickley Co. 1985. 

5. Herbert V. Vitamin E supplementation of elderly people. Am J  
Clin Nutr 1991:53:976. 

6. Herbert V. Dangers of iron and vitamin C supplements. J Am  
Diet Assoc. 1993; 93:526-7. 

7. Simopoulos AP. Herbert V. Jacobson B. Genetic nutrition:  
designing a diet based on your family medical history. New York: 
Macmillan. 1993. 

8. Herbert V. Megaloblastic anemia. N Engl J Med 1963-.268:201-3. 

9. Herbert V. Does mega-C do more good than harm, or more harm  
than good? Nutr Today 1993;28(l):28-32. 

10. Wynder EL. Hultberg S. Jacobson F, Bross IJ. Environmental  
factors in cancer of the upper alimentary tract: Swedish study with 
special reference to Plummer-Vinson (Paterson-Kelly) syndrome. Cancer 

11. Blot WJ, Li J-Y, Taylor PR, 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. 1993;85:1483-92. 

12. Steinberg D. Antioxidant vitamins and coronary heart disease,  
N Engl J Med  1993.328:1487-9. 

13. Jialal I, Grundy SM. Effect of combined supplementation with  
alpha-tocopherol, ascorbate. and beta-carotene on low-density 
lipoprotein oxidation. Circulation 1993:88:2780-6. 

14. Ran JY. Dou P. Wang LY, et al. Correlation of low serum  
folate and total B-12, with high incidence of esophageal carcinoma (EC) 
in Shanxi, China. In a high-frequency esophageal carcinoma (EC) area, 
folate and B-12 deficient subjects with esophageal dysplasia (ED) 
improve with added folate and B-12. Blood 1993; 82(suppl 1):532a. 

15. Shaw S, Jayatilleke E, Herbert V. Evidence against  
antioxidant-prooxidant vitamin C supplements protecting against cancer. 
Clin Res 1994;42:172 A (abstr). 

16. Herbert V, Shaw S, Jayatilleke E. Vitamin C supplements are  
harmful to lethal for the over 10% of Americans with high iron stores. 
FASEB J 1994;8:A678 (,abstr). 

17. Herbert V. Diet and cancer prevention. NCAHF (National  
Council Against Health Fraud) Newsletter 1992;15(3):1. 

18. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention  
Study Group. The effects of vitamin E and beta carotene on the 
incidence of lung cancer and other cancers in male smokers. N Engl 
J Med 1994-.330:1029-35. 

19. Herbert V. Shaw S. Jayatilleke E, Stopier-Kasdan T. Most 
free-radical injury is iron-related: it is promoted by iron, hemin, 
holoferritin and vitamin C, and inhibited by Desferoxamine and 
apoferritin. Stem Cells 1994; 1 2:289-303. 

20. Olson JA. Hodges RE. Recommended dietary intakes (RDI) of  
vitamin C in humans. Am J Clin Nutr 1987; 45:693-703. 

21. Olson JA. Recommended dietary intakes (RDI) of vitamin A in  
humans. Am J Clin Nutr 1987,45:704-16. 

22. Subcommittee on the Tenth Edition of the RDAs.  
Recommended dietary allowances. 10th ed. Washington, DC: National 
Academy Press, 1989. 

23. Kim I, Williamson DF, Byers T, Koplan JP. Vitamin and  
mineral supplement use and mortality in a US cohort. Am J Public Health 

24. Liebman B. Antioxidants: surprise, surprise. Nutrition Action  
Healthletter 1994;21(5):4. 

David S. Stodolsky, PhD  * Social *   Internet: 
Tornskadestien 2, st. th.   * Research *    Tel.: + 45 38 33 03 30
DK-2400 Copenhagen NV, Denmark  * Methods *  Fax: + 45 38 33 88 80

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