Is Vitamin C Dangerous?

“Study Finds Peril in Taking High Vitamin C Supplement”. So read the 2-column headline of a report by Jane Brody in the New York Times (April 5, 1998). Millions of people are bound to follow such statements as: “500 mg a day could damage people’s genes.” and “Americans must get over their love affair with vitamin C.” I felt my own credibility challenged by such statements, packaged persuasively with research conclusions from the British Journal, Nature.

As I read the article and realized how questionable are the conclusions, I wondered why was it featured so strongly. Then I caught the name, Dr. Victor Herbert, the once accomplished researcher in nutrition medicine, who has become a crusader against nutrient supplementation. Could it be that this article is propaganda? Is it but a coincidence that English health authorities currently are seeking to regulate vitamin B6 and the Food Minister has announced vitamin C is his next target?

In the 1970s Dr. Herbert claimed that vitamin C was dangerous because it oxidized and destroyed vitamin B12 in the test tube. However this was discredited when later research reversed this simply by the addition of acid, to mimic the acid conditions of the stomach. More recently Dr. Herbert emphasizes the pro-oxidant effects of vitamin C because it generates free radicals in test tube tests with copper and iron. But in reality it is well known that this reaction is used by white blood cells (neutrophils) to kill bacteria by means of the free radical hydroxyl ions so produced. This is an important part of our immune defenses. The fact is that vitamin C is used for both oxidation and reduction, in reactions that are directed by the wisdom of the body.

The vitamin C-gene damage claim came from a six-week study of 30 healthy men and women who were given 500 mg of vitamin C daily. The researchers then tested the white blood cells for oxidized adenine and oxidized guanine, two of the nucleic acid bases. They found an increase in oxo-adenine, but there was also a big decrease in the amount of oxidized guanine. A net decrease over-all; but they interpreted these findings as damage to the genetic material of DNA. The report ended with the usual call for more research, but only to study the effects of lower doses because “it would be unethical to test higher levels.”

I couldn’t believe my eyes when I caught that innuendo. How could they be that smug? What if oxo-adenine is not a sign only of damage to the genetic material of the cell? Even though their measurement technique supposedly isolates intra-cellular material from DNA, there is a possibility of other sources. For example, adenosyl methionine is found within the mitochondria of cells, where oxidation reactions are most intense. Other adenosyl molecules are found in intra-cellular enzymes, such as NAD and FAD and PAPS and this might expand the production of oxo-adenosine. The regulatory guanosine bases, on the other hand are almost entirely in the G proteins of the cell, where oxidation is less active than in mitochondria.

So I went to the scientific research literature and found that I was not alone in my doubts. Bruce Ames, professor of biochemistry, University of California at Berkeley, agrees that the Podmore study is fraught with error and that the oxo-guanine values reported by Dr. Podmore are 10 to 30 times higher than those obtained by other techniques. Dr. Ames was critical of the fact that Podmore did not acknowledge the ongoing debate about artifact and error in this area of research. He concludes: “we believe that the results.are an ex vivo artifact (in the test tube). In the context of the huge literature supporting the health benefits of vitamin C, the conclusions of the study are unwarranted.”

To say that vitamin C causes genetic damage flies in the face of evolution, in which vitamin C at larger doses offers a survival advantage. For example, a 500 mg dose is within physiologic range and vegetarians commonly exceed that amount just from food. Health statistics do not indicate damage to their nucleic acids as a result; quite the contrary, they have lower cancer rates and greater longevity. On the other hand, Jack Challem and Will Taylor suggest that lack of vitamin C might accelerate evolution by speeding up the rate of mutations, i.e. genetic damage. It makes more sense to expect that vitamin C deficiency, not excess, promotes nucleic acid damage. This theory is supported by research in living humans, not in the test tube.

The effect of vitamin C supplementation is about as perilous as breathing, which for sure exposes us to a pro-oxidizant: oxygen. The pro-oxidant effects of vitamin C are well directed and our bodies are protected. Thus the research of Dr. Balz Frei, Director of the Linus Pauling Institute at University of Oregon, clearly documents a lack of pro-oxidant interaction with iron in vivo. Here is a direct quote from Dr. Frei’s presentation at the February, 1998 meeting of the Society for Orthomolecular Medicine: “even in iron-overload plasma and in the presence of potentially redox-active...iron, vitamin C acts as an antioxidant towards lipids, not a pro-oxidant.”[i]

In other studies, Dr. Balz Frei found that both ascorbic acid and oxidized ascorbic acid (also called dehydroascorbic acid) both strongly inhibit LDL-cholesterol oxidation, even in the presence of copper, which is an oxidizer. In fact, copper binds strongly to LDL, about 30 ions per LDL particle; but in the presence of ascorbic or dehydroascorbic, up to 70 percent of the bound copper is released from LDL cholesterol due to oxidation of amino acid oxo-histidine residues, which weakens the electrical charge of the molecule, thus releasing copper to bind with circulating vitamin C for which it has a strong attraction.

Dr. Frei and his colleague, Dr. Bruce Ames, professor of biochemistry at University of California at Berkeley, co-signed a letter of criticism to the journal, Nature, regarding Dr. Podmore’s research. The key point, they say, is that the Podmore study had 1000-fold higher oxo-adducts than ever before reported. On that basis, they question Podmore’s methods and suggest that the oxo-adenine was “ex-vivo.” In other words, it formed in the test tube, not in the human body.

Stephen Fowkes, editor of Cognitive Enhancement News, wrote a particularly intelligent article for Vitamin Research News (May 1998) in which he explained the fact that DNA damage is known to occur at the rate of about 10,000 to a million damaging events per day. Our survival depends on the efficiency of our DNA repair enzymes which are designed to remove oxidized bases from the double strand helix structure of DNA. These oxidized bases are indeed markers for DNA damage—and also for DNA repair! We do not yet know whether vitamin C might enhance DNA repair, but that is very likely.

In my own review of the scientific research in this field, I was most impressed by a 1992 research at Massachusetts institute of Technology, wherein Drs. Wood and colleagues found oxo-adenine at least ten-fold less mutagenic than oxo-guanine.

Theirs was a research in a bacterium, but the point is that oxo-guanine induced defects at a frequency of 0.3%, while oxo-adenine had almost no effect on the genome. They concluded that oxoadenine is at least an order of magnitude less mutagenic than oxo-guanine in E. coli bacteria with normal DNA repair capacity.

When we apply these facts to the Podmore study, where vitamin C was associated with decreased oxo-guanine, our conclusion ought to be that the decrease in oxo-guanine more than offsets the increase in oxo-adenine. The publicity given to this research and its warnings against the use of vitamin C do a disservice to all who share an interest in health. The public has few medical sources to reassure them and is strongly influenced by information in the newspapers. As a physician and President of the Society for Orthomolecular Health Medicine, I write this rebuttal on behalf of ordinary people, who are more likely to be harmed by giving up on nutrient supplements, than by continued use of vitamin C.

Dietary ascorbic acid protects human sperm from endogenous oxidative DNA damage that otherwise affects sperm quality and increases risk of genetic defects, particularly in populations with low ascorbate status, such as smokers.

Oxo8dG is an abbreviation for 8-hydroxyguanosine, and it is a marker for DNA damage. Urine oxo8dG rises in experimental antioxidant deficiency states. In the present research, oxo8dG excretion doubled when dietary ascorbate was lowered from 250 to 5 mg per day. Meanwhile, semen ascorbate dropped by 50 percent. Increasing the ascorbate to 20 mg per day did not prevent further drop in sperm ascorbate concentration. Repletion to 250 mg per day restored seminal ascorbate to 422 mcro Mol but decreased oxo 8dG only a third (36%). Higher than expected endogenous oxidative damage to sperm means that the ascorbate offers critical protection against birth defects and infertility. Antioxidant stress puts the genome at risk; thus the increased leukemia and lymphoma in offspring of smokers may be due to damaged sperm and incomplete repair by ova-derived DNA repair enzymes.[ii]

The author observed that seminal plasma iron and copper are bound and thus unavailable to initiate lipid peroxidation. As evidence he cites the fact that oxidative damage is lowered in the presence of increased seminal ascorbic acid and incubation of semen with 60 to 1400 uM of ascorbate did not result in increased oxo8dG, as would be expected if transition metals were available to catalyze this oxidation reaction. Thus, at high levels, iron and copper are well protected in semen and ascorbate does not become pro-oxidant, even when it too is at high concentration.

How fitting that vitamin C protects the genome from mutation and enhances fertility. Linus Pauling was right again! Jack Challem has taken this insight a step further. In a brilliant analysis, published in Medical Hypothesis, he introduces the idea that the genetic disease, hypoascorbemia, has hastened human evolution. Dr. Fraga’s paper confirms that idea: DNA materials are indeed increased in animals with low concentrations of ascorbate.

That Dr. Fraga chose to dedicate this research 7 years ago to the memory of Linus Pauling on his 90th birthday is a touching gesture, both personally and intellectually. I think it means that the mind of this researcher is in agreement with the orthomolecular philosophy. The scientific genius and integrity of Linus Pauling inspired many fine scientists to conduct their research. On the other hand, the emerging orthomolecular health-medicine movement is as a peanut compared to the mountain of the medical establishment, which that is supported by governmental and industrial leaders and the media.

So great is the disparity that there would be little point to discussion were it not for the fact that in recent years the orthodox establishment doctors and bureaucrats are losing favor with their own constituency! Legislators are shifting funds into new health care delivery systems that are weighted in favor of economics rather than hope. It is a vote of no-confidence in orthodox medicine. And patients are seeking out alternative health practitioners instead of orthodox physicians.

This is not a minor trend. In fact, over half of all medical consultations in America now involve chiropractors, acupuncturists and non-psychiatric (non-M.D.) mental health workers. If nutritionists and massage therapists were included in the surveys, the disparity would be even greater. In the eyes of the public, modern medicine has failed as a source of health information and healing! Over half of the public now take vitamins to treat themselves—because their medical doctors are not prepared to do the write a nutrition prescription.

That means almost 170,000,000 Americans have decided they cannot rely on their physicians for everyday health information. Instead they are finding “alternative practitioners who offer nutritional services along with whatever else may be their special interest: massage, body movement, hypnosis, past lives, astrology, channeling, bone cracking. Holistic medicine is the combination of non-specific traditional therapy and nutrition therapy.

The most powerful factor in alternative medicine is nutrition. It is so powerful, in fact, that health food clerks and untrained personnel are sometimes able to help patients whose doctors fail them. And yet, medical authorities continue to discredit this factor, and in a recent survey on alternative medicine published in the New England Journal, nutrition was mentioned only in regards to weight loss and fitness, training, not medical treatment. The buzzword, “orthomolecular,” which refers to medical nutrition or scientific nutrition was not even mentioned in the survey.

The fact is that nutrition has been mostly excluded from consideration in the diagnosis and treatment of diseases other than a handful of fatal deficiency diseases, such as scurvy, pellagra and beriberi for the past 50 years or more. Any physician who treats with vitamins and minerals is still considered somewhat of a quack by his colleagues and is often subjected to ridicule and censure. For this reason physicians have relegated nutrition to the ‘alternative practitioners’ including chiropractors, who have attained real status in the medical arena as healers. Nutrient therapy is a major part of chiropractic practice and a reason why chiropractors have gained credibility.

Acupuncture has become popular in the United States only in the past 20 years but most of these practitioners are also familiar with Chinese herbs, which they administer along with modern nutrient products in their practices as well. Orthodox physicians meanwhile are unfamiliar with these modalities and tend to brush off the questions of their patients—mostly because they lack the training and experience to answer them. The use of the word “alternative” is actually a comfort for the conventional physician, who takes some comfort in the fact that mainstream medicine still dominates the political, economic, and cultural forces.

If this trend continues, “alternative practitioners” will increase and orthodox medicine will gradually be relegated to the emergency room and the surgical ward. Private medical practice medicine will dwindle into an executive-clerical job of dispensing medications according to rules generated by committees and policed by the insurance bureaucracy, who rely on computerized code numbers. Who will buy into such an awkward, impersonal, and soul-less bureaucratic medicine, especially when insurance claims are usually paid off at dimes on the dollar? Meantime, chiropractors and acupuncturists are paid by the self-same insurance companies—but with fewer codes and less flak and proportionately higher coverage!

It is in the context of this downward trend of the status of orthodox medicine, that the orthomolecular peanut is currently overlooked by almost everyone—except a handful of about 1000 physicians and chiropractors who think of themselves as orthomolecular. This is an important word because, while the number of proponents is small, the power of the concept is very great! Dr. Linus Pauling, the greatest scientific figure of the 20th Century, whose genius influenced the development of physical chemistry, biochemistry and molecular biology, devoted the last thirty years of his life to orthomolecular medicine. He defined this as “the use of substances that occur naturally in the human body in the maintenance of health and treatment of disease.”

Yes, Pauling was referring to vitamins, minerals, amino acids, other nutrients, hormones, enzymes and the like. Nutrition by this new name was now a real threat to the medical establishment and the backlash was fierce. Pauling was vilified, his rebuttals went unpublished in medical journals and those physicians who adopted his philosophy were singled out for censure and even delicensure. Nevertheless an orthomolecular medical society was organized and a new model of medical diagnosis and practice is in the making.

Orthomolecular medicine is the most powerful ideology in alternative medicine because it is the only one that unites basic science and clinical practice. The basic science derives from biochemistry, the chemistry of life. Nutrients play a featured role in this science, and an orthomolecular medical practice becomes thereby a practice of applied biochemistry.

[i] Berger, TM, Polidori, MC...Frei, B: (1997) Antioxidant activity of vitamin C in iron-overloaded human plasma. J Biol Chem 272,15656-15660.

[ii] Fraga CG, Motchnik PA et al: Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc Natl Acad Sci, 88:11003-11006. 1991.


©2007 Richard A. Kunin, M.D.