New Research Findings On Vitamin C Safety: An interview with Dr. Balz Frei
Part 1: The Pro-Oxidant Myth


Richard A. Passwater, Ph.D.


As mentioned in last month's interview with Dr. Sharon McDonnell, of the Centers for Disease Control and Prevention, on iron overload disorders, this interview will be with Dr. Balz Frei on the fact that vitamin C is one of the best antioxidants in vitro and in vivo (in the body) and also appears to protect against oxidative damage in the presence of iron overload in vivo.

As we were conducting the interview, a surprising and alarming news story was broadcast which incorrectly warned about alleged dangers of vitamin C supplements. Fortunately, the timing of this interview permits us to bring you the correct facts from one of the world's leading experts on the antioxidant activity and safety of vitamin C at an early date and before too many people are harmed by unadvisedly discontinuing their protective vitamin C supplements.

Balz Frei, Ph.D., the director of the Linus Pauling Institute, is well-qualified to discuss the antioxidant chemistry and safety of vitamin C. He received his Master's (1983) and Ph.D. (1986) degrees in biochemistry from the Swiss Federal Institute of Technology in Zurich. His post-doctoral research with Dr. Bruce Ames at the University of California at Berkeley from 1987-1990 involved quite a bit of antioxidant mechanistic research as you will see in this interview. Dr. Frei has also studied at The Heart Research Institute in Sydney, Australia.

Dr. Frei has held several academic positions that have permitted him to investigate both antioxidants and safety (toxicology). He was both assistant professor of nutrition in the Department of Nutrition and assistant professor of toxicology in the Department of Molecular and Cellular Toxicology at the Harvard School of Public Health. Before accepting the position of director at the Linus Pauling Institute, as well as professor of biochemistry and biophysics at Oregon State University, he was associate professor of medicine and biochemistry at the Boston University School of Medicine.

He also was the editor of Natural Antioxidants in Human Health and Disease (Academic Press, San Diego, 1994) and has served oil the editorial boards of Archives of Biochemistry and Biophysics (1993-1996), Redox Report (1996-present) and Free Radical Biology Medicine (1997-present).

In 1993, 1 recognized Dr. Frei's report in the Journal of Biological Chemistry pointing out that the result of vitamin C biochemistry was an antioxidant effect even in the presence of metal ions to bc of major- importance as it was a seminal paper that eventually would lead to a clearer understanding of the effectiveness and safety of vitamin C. I made it a practice to always carry a copy of that report in my briefcase and it came in handy many times.

My first meeting with Dr. Frei was at the FDA Conference on "Antioxidant Vitamins and the Prevention of Heart Disease and Cancer," which was held at the National Academy of Sciences in November 1993. When we were introduced to each other, I think it surprised him that I could bring forth a tattered copy of his report from my briefcase.

The Linus Pauling Institute was established at Oregon State University in August 1996 under an agreement reached between its antecedent organization, the Linus Pauling Institute of Science and Medicine, and Oregon State University. Oregon State University established the Linus Pauling Institute to honor its remarkable 1922 alumnus. Dr. Pauling died in 1994 at the age of 93. 1 think that this is the first time that I have been able to write about him since that time. I still have two unpublished interviews with him that I probably will never bring my self to publish because of the sadness it brings to my mind.

Passwater: Dr. Frei, congratulations on becoming the director of the Linus Pauling Institute. This is a very coveted position. Several of my academic friends applied, but no one can think of anyone better than you to assume this responsibility. Thank you for caring enough to take it on. With the Linus Pauling Institute moving "home" to Oregon State University and you leading the way, what can we now expect from the Linus Pauling Institute?

Frei: Thank you for those kind words. I am indeed excited to have the opportunity to lead the Linus Pauling Institute in the coming years. I believe the Institute has great potential to become a leading research institute in the area of nutrition and micronutrients and their role in human health and disease. In fact,' the mission of the Linus Pauling Institute is to investigate the role of micronutrients, microconstituents of food and phytochemicals in maintaining human health and preventing and treating disease; and to advance our knowledge in areas that were of interest to the late Dr. Linus Pauling.

As you know, Dr. Linus Pauling is the only scientist ever to will two unshared Nobel prizes, one in Chemistry in 1954 and the Nobel Peace Prize in 1962. His interests spanned from chemistry to molecular biology to orthomolecular medicine and nutrition. The research pursued at the Institute will focus primarily on Dr. Pauling's major interest in die last 20 to 30 years of his life, i.e. to determine the optimal concentrations and functions of micronutrients and other dietary factors in the human body We are, of course, talking about the field of orthomolecular medicine.

In addition to performing and sponsor-ing research at Oregon State University, the Linus Pauling Institute will, among other things, organize and support conferences related to nutrition and health, support the Linus Pauling Institute visiting professor, publish a newsletter twice a year and have all outreach program to educate the lay public on issues of nutrition, vitamins and micronutrients.

Passwater: Dr. Pauling was very interested in your work ever since you published the 1989 PNAS paper showing that vitamin C was the most important antioxidant in the bloodstream (Proc. Natl. Acad. Sci. 86:6377-6381). Of all your goals for the Linus Pauling Institute, what research will you, yourself be focusing on?

Frei: The research in my laboratory will continue to focus oil the role of vitamin C and other dietary antioxidants in inhibiting atherosclerosis and other oxidation processes related to heart disease and stroke. We are particularly interested in the role of the intracellular redox state, as determined by vitamin C, vitamin E and glutathione, in the regulation of transcription factors and adhesion molecules, which are important in the recruitment of monocytes to the arterial wall in the early stages of atherosclerosis.

In collaboration with my colleagues at Boston University, we are also continuing to investigate the role of vitamin C in endothelial function in patients with coronary artery disease and have recently shown that both acute (2 grams of vitamin C, 2 hours) and chronic (500 mg of vitamin C/day for 30 days) supplementation improve vasomotor function in patients with coronary artery disease. This indicates that vitamin C can lower the risk of a myocardial infarction (heart attack).

Another focus of my lab is the investigation of the potentially pro-oxidant effects of vitamin C in the presence of iron. As you know, iron and vitamin C exert pro-oxidant effects in vitro, and this has been hypothesized to be of relevance in vivo. However, there is only anecdotal evidence and no scientifically valid data on the pro-oxidant effect of vitamin C in vivo. [As far as I am concerned, this question remains to be systematically and thoroughly investigated.

This issue also currently is of considerable importance because of the discussion of a new RDA for vitamin C by the Food and Nutrition Board of the Institute of Medicine. Therefore, we are doing experiments to either support or refute tli6 hypothesis that vitamin C acts as a pro-oxidant in vivo in the presence of iron over load conditions.

Passwater: Yes, there is a "pro-oxidant myth with vitamin C." Why or how did you become interested in antioxidants and vitamin C?

Frei: I first became interested in the antioxidant role of vitamin C when I was a postdoctoral fellow in Dr. Bruce Ames' laboratory at the University of California at Berkeley. I was investigating the antioxidant defense systems in human blood plasma in different types of oxidative stress and measuring the consumption of endogenous antioxidants in relation to the formation of lipid hydroperoxides. During those studies. I discovered that vitamin C forms the first line of antioxidant defense in human plasma, and, in fact, vitamin C was the only endogenous antioxidant that completely protected the lipids in plasma against oxidative damage.

Initially, I used a chemical radical initiator called AAPH to oxidize plasma, but later I showed that vitamin C also forms the first line of antioxidant defense in plasma exposed to pathologically more relevant types of oxidative stress, such as cigarette smoke, activated neutrophils and the xanthine/xanthine oxidase system. These observations were relevant to the pathogenesis of atherosclerosis, as lipid peroxidation and oxidative modification of low density lipoprotein (the LDL or so-called bad cholesterol) have been implicated as important contributing factors in atherosclerotic lesion formulation. Therefore, my findings suggested that vitamin C can lower the risk of heart disease and stroke through inhibition of LDL oxidation

Passwater: Your first papers seem to be oil calcium release in mitochondria. Does oxidation have a role in this?

Frei: Yes, that is true. During my thesis work in Dr. Christoph Richter's lab at the Swiss Federal Institute of Technology, I investigated the role of oxidative stress in the release of calcium from rat liver mitochondria. We found that organic hydroperoxides, such as tert-butyl hydroperoxide, as well as hydrogen peroxide, can cause the release of intra-mitochondrial calcium by a mechanism involving glutathione peroxidase, glutathione reductase, and an NAD+ glycohydrolase.

This results in ADP-ribosylation of a protein, opening up a calcium gate or channel and leading to the release of calcium from the mitochondria. It is therefore likely that under conditions of oxidative stress mitochondrial calcium release leads to an inbalance in the cytoplasmic calcium concentration, which can have further important downstream consequences; these may include activation of proteases and phospholipases and even cell death.

Passwater: You also studied coenzyme Q-10. What did you find?

Frei: I did a limited number of studies oil coenzyme Q-10, and in particular on its reduced form, ubiquinol-10. These studies showed that ubiquinol-10 is a good lipid-soluble antioxidant at physiological concentrations, about as good as or even better than alpha-tocopherol (vitamin E). I'hey also showed that ubiquinol-10 can spare alpha-tocopherol, but not vitamin C. We further showed that ubiquinol-10 forms the first line of antioxidant defense within LDL and is consumed before alpha-tocopherol or the carotenoids when LDL is exposed to oxidative stress.

However, ubiquinol-10 concentrations in LDL are very low, usually less than one molecule per LDL particle, and it is therefore not clear whether tibiquinol-10 contributes significantly to the antioxidant protection of the lipoprotein. This is different from membranes if) particular the inner mitochondrial membrane where coenzyme Q-10 is present a relatively high concentrations and thus likely to play an important antioxidant role, in addition to its function as an electron carrier in the mitochondrial respiratory chain.

Passwater: What I have found to be most exciting about your research are your studies showing that vitamin C results in a net antioxidant effect and not a pro-oxidant effect in the presence of metal ions and in vivo. As a clarification to some of our newer readers, in vivo merely is the biochemist's jargon meaning a process occurring in real living bodies, as opposed to in vitro, which refers to lest tube or glassware experiments. Ex-vivo refers to experiments where compounds removed from living bodies are then treated in laboratory equipment. For those who haven't read this paper yet, the abstract and bibliographic details are presented in Box 1 (see Page 90). What led to your interest in this area?

Frei: In this article, we investigated tile role of vitamin C in protecting LDL against copper-induced oxidation. Copper-induced oxidation is used commonly to assess the resistance of LDL to oxidative modification, although it is not clear whether copper plays a role in LDL oxidation in vivo in the arterial wall. However, recent evidence indicates that ceruloplasmin, a copper-containing protein, can oxidize LDL and is present in atherosclerotic lesions.

Interestingly, as I mentioned earlier, vitamin C may act as a pro-oxidant in the presence of transition metal ions such as iron or copper, at least in vitro, and therefore in our studies we expected vitamin C to exacerbate, rather than inhibit, copper-induced LDL oxidation. Quite to the contrary, however, we observed that physiological concentrations of vitamin C very strongly inhibited oxidative modification of LDL, as assessed by a number of different methods including consumption of LDL-associated antioxidants, lipid peroxidation, apo B modification and increased recognition of LDL by the macrophage scavenger receptors.

The latter is an important endpoint of LDL modification, as uptake of LDL via the scavenger receptor pathway leads to the conversion of macrophages to foam cells in tile arterial wall. Out- data, therefore, strongly suggested that vitamin C can prevent the modification of LDL that otherwise would result in foam cell formation.

Interestingly enough, we also found that the oxidized form of vitamin C, called dehydroascorbate (as compared to ascorbate, which is the reduced form of vitamin C), very strongly protects LDL against copper-induced oxidative modification. While we have not completely elucidated the mechanism of this paradoxical protective effect of ascorbate and dehydroascorbate against copper-induced LDL oxidation, we have evidence that copper in the presence of ascorbate or dehydroascorbate causes oxidation of histidine residues of apo B in LDL to 2-oxohistidine. As copper binding to apo B is a prerequisite for copper-induced LDL oxidation, and histidine residues act as primary copper binding sides oil apo B, tile conversion of these residues to 2-oxohistidine may result in the release of bound copper from LDL and thus inhibition of copper-mediated LDL oxidation.

In support of this hypothesis We have found that incubation of LDL and copper with ascorbate or dehydroascorbate leads to the rapid decrease of bound copper ions per LDL particle from about 30 to 10, which is associated with the inhibition of LDL oxidation

Passwater: Let's talk some more about the "pro-oxidant myth - A critic of vitamin C supplementation has Spent much effort in spouting off with untrue warnings about vitamin C that have prevented many people from taking advantage of this protective antioxidant nutrient This bad advice has harmed those individuals. Let's look at the implications of your research regarding vitamin C's in vivo antioxidant status. Skeptics were concerned that higher vitamin C levels from supplements would increase oxidation by increasing the production of hydroxyl radicals by reacting with "free" unbound iron in the body via Fenton and Haber-Weiss reactions. What are those reactions and what have you found?

Frei: The pro-oxidant activity of vitamin C in the presence of free iron in vitro is explained by the Fenton and Haber-Weiss reactions. The Haber-Weiss reaction is the metal-catalyzed production of hydroxyl radicals in the presence of superoxide and hydrogen peroxide; it consists of two separate reactions. In the first reaction, the metal ion is reduced from its oxidized form to its reduced form, such as Fe3+ or ferric to Fe2+ or ferrous iron, and this reduction occurs by superoxide, which itself is oxidized to oxygen. It is the reduced metal ion that causes most of the oxidative damage, because in the so-called Fenton reaction the reduced metal ion reacts with hydrogen peroxide to form hydroxyl radicals, which are extremely reactive and can cause oxidative damage. The chemical formula reactions are shown in Box 2 (see above).

Now, the initial reduction of the metal ion starting this chain of events can be done by superoxide or a number of other reductants or antioxidants, including vitamin C, vitamin E, and glutathione. However, whether these same reactions also occur in vivo is not clear. It is a mystery to me why vitamin C always gets singled out as a potential pro-oxidant in vivo, and not also other antioxidants, including vitamin E.

We have done a number of experiments to address this important issue of a potential pro-oxidant effect of vitamin C in biological fluids or in vivo in the presence of excess iron.

For example, we have investigated the blood levels of lipid peroxidation and protein oxidation products in premature infants, many of whom are born with free iron in their blood plasma (J. Biol. Chem. 272:15656 1997). This free iron can be detected by the so-called bleomycin assay. In our study, about two-thirds of the infants had bleomycin-detectable iron in their plasma, whereas the remaining third did not. However, there was no difference in the levels of protein or lipid oxidation products between the infants with bleomycin-detectable iron and those without, indicating that the bleomycin-detectable iron itself did not cause oxidative damage.

In addition, we investigated possible correlations between bleomycin-detectable iron, ascorbate and increased oxidative damage, but again we were not able to find any significant correlations. These data suggest that ascorbate together with bleomycin-detectable iron does not cause oxidative protein or lipid damage in these premature infants.

Furthermore, we recently completed an animal study using iron-overloaded guinea pigs that were fed high or low doses of vitamin C. Guinea pigs were used in these studies because they, like humans, lack the ability to synthesize vitamin C. Again, we measured lipid peroxidation products and found that those guinea pigs loaded with iron did not have increased levels of lipid oxidation products in plasma or liver. However, those guinea pigs that were fed high vitamin C levels had less lipid oxidative damage than those guinea pigs that were fed the low levels of vitamin C, independent of iron loading. These in vivo studies, therefore, indicate that vitamin C acts as an antioxidant against lipid peroxidation, even in the presence of massive iron overload.

Finally, we also did experiments using human plasma that was loaded with iron in vitro followed by addition or depletion of ascorbate and measurement of lipid hydroperoxide formation. In confirmation of our guinea pig studies and the analysis of plasma samples from premature infants, these studies with iron-supplemented plasma demonstrated that vitamin C acts as ill antioxidant and strongly protects against, rather than promotes, iron-induced lipid peroxidation.

Taken together, these data show that there is not a pro-oxidant effect of vitamin C and iron on lipids and proteins in biological fluids such as plasma or ill vivo. Therefore, the pro-oxidant effect of vitamin C observed in the presence of iron in vitro does not seem to be relevant to the in vivo situation. We are now following up on these observations, investigating other types of iron loading in guinea pigs as well as doing additional studies in humans.

Passwater: Do the data indicate that there are no pro-oxidant effects in vivo, or do they indicate that the total overall effect is an antioxidant effect rather than all overall pro-oxidant effect?

Frei: That's an interesting question. What we can say with certainty at this point is that Vitamin C protects against iron induced lipid peroxidation and does not cause oxidative protein damage in iron overload conditions in vivo.

We have not specifically investigated the question of whether vitamin C protects against iron mediated DNA damage Several human and animal studies done by other investigators have shown that vitamin C acts as an antioxidative DNA damage in vivo. The mechanism of the overall antioxidant effect of vitamin C against iron-induced lipid peroxidation is not clear, but may involve a pro-oxidant step. We know that in plasma vitamin C reacts with iron, i.e. reduces ferric to ferrous iron, and this may result in hydroxyl radical production by Fenton chemistry. However, these radicals seem to be scavenged by vitamin C, thereby resulting in an overall protective or antioxidant effect.

Passwater: I also have seen publications by Drs. Gladys Block and Barry Halliwell which support and complement your observations. I fondly remember Dr. Block's editorials in The Journal of the National Cancer Institute (J Natl Cancer Inst. 83 (8):547-550 April 17, 1991) and the Annals of Internal Medicine (Ann Intern Med 114(10):909-910 15 May 1991) that changed how scientists viewed the vitamin C research of Dr. Pauling forever. Until that time, many scientists were ignoring Dr. Pauling's vitamin C research.

Of course, Dr. Block is now at the School of Public Health at tile University of California at Berkeley, but at that time she was with tile National Cancer Institute which helped give vitamin C all official "blessing." The National Cancer Institute and the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a landmark symposium during September 1990 oil the biologic function of Vitamin C and its relation to cancer. In both editorials, Dr. Block, along with her co-authors Drs. Donald Henson and Mark Levine, reviewed the research presented at the symposium. The net effect was that Dr. Pauling's research was taken seriously and it then became OK for "serious" scientists to research the protective effect of vitamin C against cancer.

In fact, I remember that you were still at the Department of Nutrition at the Harvard School of Public Health and you opened the symposium by reporting on your research on vitamin C as the strongest antioxidant in plasma that can completely protect blood lipids such as LDL from oxidation. You later published this in the American Journal of Clinical Nutrition ( Am J Clin Nutr 54:1113S-1118S; 1991). During the symposium, Dr. Block summarized 33 epidemiologic studies showing that vitamin C is significantly associated with reduced cancer incidence and mortality.

Frei: Dr. Gladys Block has published extensively on the epidemiological evidence in support of a protective role of vitamin C in lowering the risk of different types of cancer. In one of her review articles she has summarized the evidence that a diet high in vitamin C, i.e. rich in fruits and vegetables, is associated with a decreased risk of many different types of cancer, in particular cancer of the mouth, throat, esophagus, stomach and pancreas.

She also has recently done a very intriguing study on the association between iron status and vitamin C status in hemochromatosis patients. This study has shown, in agreement with our own studies, that increased iron status is not associated with increased oxidative damage, and that vitamin C intake is inversely associated with markers of oxidative damage in hemochromatosis patients.

Passwater: I remember seeing one of her presentations in which she reported that "high plasma vitamin C significantly (p=0.0008) reduced oxidation damage (lipid peroxidation) rather than increasing it. No other plasma antioxidants were as strongly associated with reduced oxidative damage."

Frei: She also was involved in a study with the National Cancer Institute and the U.S. Department of Agriculture showing that increased plasma ascorbate levels are associated with decreased blood pressure. Finally, in another carefully performed and controlled study she showed that vitamin C status has a significant impact on high-density lipoprotein levels. Previous studies had also indicated that vitamin C intake is associated with increased HDL levels. It seems, therefore, that vitamin C can lower the risk of heart disease through a number of mechanisms, including inhibition of LDL oxidation, lowering of blood pressure and increasing HDL levels.

Passwater: I noticed that Dr. Barry Halliwell, whose home base is at the International Antioxidant Research Centre at Kings College (London), and his colleagues presented a study at the Oxygen Society of California's February meeting in Santa Barbara that examined the co-supplementation of iron with vitamin C in healthy volunteers. They found that initially transferrin saturation increased slightly, but remained in the normal range, but by 12 weeks, returned to the initial level. 'Me interesting point was that blood platelet aggregation (blood stickiness or tendency to clot) significantly decreased in those receiving the higher doses of vitamin C thus decreasing the risk of a coronary thrombosis. Total DNA oxidation markers were at approximately the same as the initial values after 12 weeks of supplementation.

They concluded that "supplementation with iron and vitamin C showed beneficial effects, including decreased sensitivity of blood platelets to aggregation and increased plasma vitamin E levels.

Frei: Dr. Barry Halliwell had collaborated with us on the study mentioned earlier-the one on protein and lipid oxida-tion markers in premature infants, and he has extensively published on the potential role of bleomycin-detectable iron in oxidative damage. He also showed many years ago that under normal conditions, i.e. in healthy subjects, there is no free iron floating around, but instead iron is bound to specific proteins, such as transferrin and ferritin.

Dr. Halliwell also has written many authoritative review articles that very carefully and in great detail examine the scientific evidence in support of a pro- or antioxidant role of vitamin C in vivo. The conclusion of these review articles is that there is no secure evidence that vitamin C acts as a pro-oxidant in vivo, and that there is only anecdotal evidence that this may be the case under very specific conditions and in some isolated cases. However, the overwhelming evidence is in support of an antioxidant, and thus beneficial, role of vitamin C.

Passwater: Now how's this for timing! As we are chatting, there is news of a "study" published as "correspondence" in Nature that is grabbing the headlines because it alleges that vitamin C supplements may cause harm and even cancer. Have you received your copy yet?

Frei: Yes, this study is poor science, and I am very surprised that it was published in Nature, even if it is "only" in the correspondence section. The study claims that supplementation by humans with 500 mg of vitamin C per day causes oxidative DNA damage, i.e. genetic damage, in a type of white blood cells called lymphocytes. The study has so many flaws, I don't even know where to start. The two biggest ones are its poor design, which is completely unacceptable by current standards and guidelines for testing a compound in a clinical trial, and the methodology for measuring oxidative DNA damage

Passwater: It appears as if they looked at just two biological markers of oxida-tive damage, and one went down (8-oxoguanine) which is good and could help explain how vitamin C is protective, and the other (8-oxoadenine), which is a questionable marker at best, went up. Even if they were equivalent markers, it would be a wash, but the marker of oxidation that improved (decreased) is at least 10 times more mutagenic than the other.

Aren't there about 18 or 20 markers that should be considered, and isn't the methodology for measuring oxidative DNA adducts very tricky? I believe that the senior researcher in the group reporting in Nature, Dr. Joseph Lunec, himself has discussed this ill the literature. The topic of two of Dr. Lunec's papers concerns the artifacts (false results) produced by the method used to extract DNA from the cells. Also, I find it interesting that a Medline search of the literature indicates that two of his papers since 1994 have had "errata" published. They don't even mention this in their "correspondence."

Frei: Yes, measuring oxidative DNA damage is very tricky and, in fact, more I work in progress than a "done deal." The authors of the Nature study are very much aware of the current controversy surrounding the accurate measurement of oxidative DNA damage. They used a method known to lead to massive ex vivo artifacts. As a result, the levels of oxidative DNA damage reported in the Nature study are at least tenfold, but more realistically about one thousand-fold higher than what other scientists have published and is the currently acceptable level of oxidative DNA damage in human lymphocytes. This means that 90%, bill more likely 99.9%, of the oxidative DNA damage in the Nature study was created ex vivo rather than occurring in vivo. Such data are obviously useless.

Passwater: Do you have experience in this type of measurement? If so. What have you and others found with vitamin C and oxidative DNA damage?

Frei: As mentioned earlier, several studies have investigated the roll. of vitamin C in preventing oxidative DNA damage. A number of years ago, Dr. Bruce Ames did a study in collaboration with Dr Bob Jacob at the USDA Western Nutrition Research Center in San Francisco. This research showed that in 10 males vitamin C depletion resulted in oxidative damage to sperm DNA, which was then reversed by vitamin C repletion.

Other studies also have found a protective effect of vitamin C supplementation against oxidative DNA damage, or no effect. Not a single study has found increased oxidative DNA damage with vitamin C supplementation.

In this respect, one animal study is particularly noteworthy. In this study, there was a 60-fold difference in liver vitamin C levels between vitamin C-fed and vitamin- C-depleted guinea pigs, but no difference in the levels of oxidative DNA damage.

Passwater: With all of this uncertainty, I wonder why they felt compelled to rush this out as correspondence rather than confirming their observations and going through the normal peer review process--especially when there are hundreds of research reports indicating that vitamin C is protective against cancer and safe to use as a supplement even at high doses?

Frei: One has to wonder. Indeed, I have heard rumors that the decision to publish was a political one rather than a scientific one. The result is that Nature and Dr. Lunec and his group have lost credibility and] respect among their scientific peers. Also, the public is scared about a nonexistent danger. That's the real damage that this study has done.

Remember, too, that once the message has been released by the press in an unfiltered fashion, it is almost impossible to get it straightened out.

Passwater: There is no question about that. Nevertheless, we must try to get wrong stories righted, and your willingness to participate in interviews like this one play an important part in this effort

Dr. Frei, let's break the conversation at this point. Next month in Part 2, we'll go into more detail oil the relationship between vitamin C and iron overload disorders, in addition to discussing some of the future plans for the Linus Pauling Institute.

Copyrighted 1998 by Whole Foods magazine , Whole Foods Incorporated. Reprinted with the permission of the copyright owner. No distribution of any kind permitted without the permission of the copyright owner or Solgar Vitamin & Herb Co., Inc.