Can You “C” a Difference?

Thirty years ago, Nobel Prize-winning chemist Linus Pauling, PhD, shook the health community with his book Vitamin C and the Common Cold, in which he proposed that large doses of C, or “megadoses,” could cut the duration of the common cold in half. The book sparked a continuing controversy over the doses and benefits of vitamin C, and helped spawn a multi-billion-dollar industry.

Less known is the pioneering work of Fredrick R. Klenner, MD, who in the late 1940s was said to have cured more than 60 cases of polio and other types of life-threatening viral infections with megadoses of ascorbic acid. His work was well-documented in a number of peer-reviewed medical journals. Contemporary MDs such as Abram Hoffer, Robert Cathcart, Hugh Riordan, and others continue this research and use megadoses of vitamin C as integral parts of effective treatment for health conditions as mild as seasonal allergies or as serious as advanced cancer, and in the prevention of diseases as disparate as sudden infant death syndrome in the beginning stages of life and Alzheimer’s toward the end.

In 1968, Pauling coined the term “orthomolecular” medicine to describe a nutrition-based approach to health intended to balance elements naturally present in the human body. While there is universal agreement among orthomolecular physicians that people must supplement their diets with vitamin C to remain healthy—and that the USRDA standards, developed by the U.S. Academy of Sciences, are far too low—there is considerable disagreement over what levels need to be maintained, and what forms of vitamin C are most beneficial.

A quick trip to a natural food store reveals that vitamin C is available in an overwhelming number of forms. There are capsules and powders, time-release pills and chewables. Pill potencies range from 100 mg to ten times that amount. Vitamin C can come as simple ascorbic acid or in “buffered” forms of mineral ascorbates, such as calcium ascorbate, magnesium ascorbate, and so on. There are also dozens of different C-based supplement formulas, with added minerals, other vitamins, or naturally occurring cofactors such as bioflavonoids. And the range of prices for vitamin C products is as great as the number of forms they come in.

To treat life-threatening illnesses, many alternative physicians administer vitamin C intravenously in order to achieve extremely high levels in the blood plasma and tissues (although they often combine this with an oral product regimen). The reason for this is that when vitamin C is ingested orally, the body regulates how much can be absorbed from the gastrointestinal tract into the bloodstream and utilized by cells. These are issues of bowel tolerance (a limiting factor for absorption) and bioavailability (how much is actually used by the cells, as opposed to how much is simply excreted through the kidneys). The differences among all the available vitamin C products are primarily focused on improving these two factors.

When individuals take more than a certain amount of vitamin C within a short period of time, it can cause diarrhea. The basic mechanism of bowel tolerance seems to be a function of the acidity of ascorbic acid, or simple vitamin C. Like any acidic food, when we ingest ascorbic acid, the body neutralizes it by combining the acid with minerals—in this case, most commonly with potassium or sodium. The ascorbic acid becomes a salt—potassium ascorbate or sodium ascorbate—which attracts water into the colon, creating loose bowels to expel it from the body.

The amount of vitamin C it takes to reach the threshold of bowel tolerance varies tremendously from individual to individual, and even within the same individual, depending on his or her condition. Many studies indicate that the sicker a person is, the more vitamin C he or she will naturally tolerate, by an astounding factor of ten or more.

Forms of Vitamin C

Ascorbic acid

The most common form of vitamin C is simple ascorbic acid. This is a naturally occurring, water-soluble, acidic compound that comes in pills, powders, and as an ingredient in multivitamins. In two recent peer-reviewed scientific studies on humans, health results did not significantly differ between natural ascorbic acid (such as the C in orange juice) and the synthetic ascorbic acid of vitamins, or between powders, tablets, time-release capsules, or chewables. Those studies are listed at the website of the Linus Pauling Institute (

To offset the acidity thought to cause the gastrointestinal problems associated with the vitamin, Pauling added baking soda (a base) to his doses. However, within the federally recommended maximum levels of up to 2,000 mg per day, ascorbic acid shouldn’t cause a problem for most people.

But that’s a low dose to some vitamin C devotees. Therefore, experts have recommended that people with stomach ulcers or those who experience nausea or other gastric problems with higher doses of vitamin C opt instead for a buffered form, or take lower doses of ascorbic acid with meals. In theory, food helps increase vitamin C absorption by slowing the rate at which the vitamin leaves the stomach—giving it more time to pass into the bloodstream.

Buffered C

Several forms of vitamin C are mixed with buffering agents to make them gentler on the body than pure ascorbic acid. Among those buffering agents are calcium carbonate, sodium carbonate, and magnesium oxide. When combined with ascorbic acid, those buffers create what are known as “mineral ascorbates.” (The suffix “-bic” in ascorbic means it’s an acid, while the “-bate” in ascorbate means it’s a salt.)

Mineral ascorbates are actually the form of vitamin C that is produced in the livers of animals that manufacture their own C. When humans ingest ascorbic acid, our bodies attempt to change it into an ascorbate in the intestines by combining it with minerals. The main mineral ascorbates found in the body are potassium, sodium, calcium, and magnesium ascorbates. Although it occurs within our body naturally, potassium ascorbate is the one form that can be fatal if supplemented at extremely high doses (approximately 18 grams).

Commercial vitamin C products that are already in the form of ascorbates offer protection against excess acidity from the get-go, and save our bodies the trouble of having to draw on minerals to make the conversion. Many clinicians recommend taking vitamin C as a mixture of the various mineral ascorbates. Among them is Neil Riordan, CEO of the Aidan Clinic in Tempe, Arizona, which treats cancer patients with very high doses of IV vitamin C. Aside from being less acidic, Riordan says, a mixed ascorbate offers the added benefit of other nutrients, such as calcium. “For someone who is taking 500 mg to 1 gram a day, that gives them some other minerals as well.”

Calcium ascorbate is the most common of the mineral ascorbates on the market. Richard Passwater, PhD, author of Supernutrition, calls calcium ascorbate the “ideal” form of vitamin C for two reasons: It eases digestion and replenishes calcium.

Vitamin C at megadose levels binds with metals like lead, mercury, and cadmium, and flushes them from our systems. That process, however, can also end up flushing out essential minerals like calcium, magnesium, iron, copper, and zinc. Passwater notes that most people who are deficient in vitamin C are already suffering from reduced levels of calcium, so the use of calcium ascorbate solves two problems at once.

Pure calcium ascorbate provides 57 mg of calcium per 500 mg of ascorbic acid, and calcium in this form appears to be easily absorbed, according to the Linus Pauling Institute. The recommended dietary calcium intake for adults is 1,000 mg to 1,200 mg daily (not to exceed 2,500 mg), according to the National Academy of Sciences. An added benefit of calcium ascorbate, Passwater says, is that calcium helps the body absorb ascorbate—the productive part of vitamin C—by temporarily protecting it from oxidation.

Besides calcium ascorbate, sodium ascorbate is also available in powder form, but has the drawback of raising blood pressure. Sodium ascorbate generally provides 65 mg of sodium per 500 mg of ascorbic acid. People with high blood pressure are usually advised to keep sodium intake to less than 2,500 mg per day from all sources.

With cofactors

Several nutrients are thought to help vitamin C work more efficiently, making lower doses possible. While authorities such as the Vitamin C Foundation and Dr. Robert Cathcart stand by Pauling’s theory on the subject—that additives such as rose hips or flavonoids are more of a marketing gimmick than anything else—many health food stores and natural vitamin producers steer customers to supplements containing flavonoids, vitamin K, and the B vitamins niacin and biotin.

Also known as bioflavonoids, flavonoids are a class of water-soluble plant pigments that occur naturally in fruits and vegetables and act as antihistamines and anti-inflammatory and antiviral agents. Sometimes referred to as vitamin P, flavonoids have been used to treat a number of health conditions, including capillary fragility and bruising. Flavonoids, in general, are thought to prevent the destruction of vitamin C in the body by oxidation. Citrus flavonoids, specifically, are thought to help in vitamin C absorption.

The Linus Pauling Institute cites only two clinical studies on the potency of vitamin C in conjunction with flavonoids, which have conflicting results. One showed no difference in potency at all. But one study by Joe A. Vinson, PhD, published in 1988 in the American Journal of Clinical Nutrition, showed that 500 mg of synthetic ascorbic acid in a natural citrus extract containing bioflavonoids, proteins, and carbohydrates was absorbed more slowly—and thus more efficiently—than pure ascorbic acid. Yet the Institute points out that the study had a 4:1 ratio by weight of bioflavonoids to ascorbic acid—a much higher amount than that contained in most commercially available products.

To many people, it just makes sense to take supplements in forms as close as possible to how they occur in nature, and the vitamin C that occurs in nature is always a form of ascorbic acid accompanied by a number of bioflavonoids and other cofactors. Thus, many vitamin C manufacturers add not only bioflavonoids to their formulas, but vitamin C-rich whole-food concentrates, such as rose hips or acerola cherries. There seems to be no definitive clinical data that this approach actually makes the products work better. However, it has been well-established that the actions of many nutrients are not due to one isolated element, but the synergistic interactions of a whole range of elements. So, even if the synergistic mechanisms are not understood, taking supplements with cofactors is a safe way to hedge one’s nutritional bet.

Neil Riordan is one who believes in the use of cofactors. He says he has achieved dramatic results by using alpha-lipoic acid, vitamin K, and selenium to enhance the effects of his clinic’s vitamin C therapies. In an article published in the June 2001 British Journal of Medicine, Riordan explained the clinic’s findings that alpha-lipoic acid could potentiate the effects of vitamin C fivefold in an IV solution. As a result of those findings, Riordan says the clinic now uses a pill called IVC-Max, which combines alpha-lipoic acid, vitamin K, and selenium, for its patients. It also sells the pills to physicians who administer high dosage vitamin C therapies to their own patients.

Many health food stores recommend a trademarked version of C known as Ester-C, which addresses both the ascorbate and cofactor issues. Ester-C is made up of calcium ascorbate, with the bioflavonoids quercetin, rutin, and proanthocyanidins. On its website, NutriCology, a supplier of Ester-C products, contends that its studies indicate that Ester-C is absorbed faster into the bloodstream and by white blood cells, and that it maintains higher blood and tissue levels than other forms of vitamin C. However, according to the Linus Pauling Institute, the only published peer-reviewed study on the topic found no difference in the absorption of Ester-C and ascorbic acid tablets. Nevertheless, many nutritionists claim superior anecdotal results using Ester-C.

Other technologies

Just coming on the market now is a product by BioImmune Inc. called Ascorbic-C. The company has tested it by supplying it to clinics employing high-dose vitamin C therapy, including the Robert Atkins Center in New York and the Livingston Foundation Medical Center in San Diego, California. According to BioImmune president Arnold Takemoto, the secret of Ascorbic-C is a special micro-encapsulation of pure, beet-derived ascorbic acid within extremely stable membranes of essential phospholipids. Takemoto claims that this process prevents bowel intolerance, because the ascorbic acid is not released in the GI tract. The product’s phospholipids are the same material as intestinal villi and are so small—able to be seen only with an electron microscope, he says—that they easily pass into the bloodstream, and can enter cells and cross the blood-brain barrier. The capsule only starts to gradually break down in the bloodstream and in cell tissues, says Takemoto, giving it a time-release function that allows the body to maintain high levels for extended periods of time.

Ascorbic-C comes in jars of 2 fluid ounces, containing 10 grams of ascorbic acid. The micro-encapsulation process is expensive, which puts this product on the high end of the price range. Again, there are no studies substantiating that the product does produce extended levels of high vitamin C concentrations in blood plasma or tissues. However, the clinics that have been using the product report good results. Douglas Brodie, MD, in Reno, Nevada, who has used vitamin and mineral infusion as part of his practice for many years, says, “So far, Ascorbic-C seems to be living up to its claims.”

Plant-grown or cultured C

Expanding on the whole-food concept, another novel approach is taken by two companies—LifeStar Millennium and NewChapter—that offer what LifeStar calls “plant-grown” and NewChapter calls “cultured” vitamin C. Joe Bentley, founder of LifeStar Millennium in San Rafael, California, maintains there is a huge difference between taking single chemical compounds and taking vitamins alongside other nutrients. Using yeast found naturally in grapes, the company grows an array of vitamins in what Bentley says is the natural state for human consumption. The approach produces a vitamin pill with nutrients that would occur naturally alongside vitamin C. As a result, he says, our bodies perceive it as a natural product instead of a foreign item to be discarded as waste. This addresses the issues of both bowel tolerance and bioavailability.

Bentley has testimonials from customers who have taken up to 50 grams over a 24-hour period with no stomach upset or diarrhea. And he claims that because the vitamin C is contained in the yeast, it is a whole food, able to be stored in our systems for about a week. That’s compared to 24 hours for most ascorbic acid.

There is no clinical data to substantiate this claim, but LifeStar does have a study on its website showing that its vitamin C has several times more antioxidant activity than pure ascorbic acid and certain other vitamin C products. This 1997 study was commissioned by the developer of the plant-grown process, and compared the ability of four different products to inhibit the oxidation of low-density lipoproteins—otherwise known as “bad” cholesterol. The study shows that the plant-grown form of vitamin C had 11.1 times more antioxidant activity than pure ascorbic acid. Therefore, theoretically, taking just one 500 mg pill of plant-grown C has the equivalent antioxidant protection of 5,500 mg of synthetic C.

Doses for Daily Health

It seems that everyone has a different opinion on how much vitamin C adults should take. At the most conservative end are the USRDA recommendations, which now advise 90 mg per day for healthy adult men and 75 mg for women, while urging smokers of both genders to add 35 mg to those amounts. 

Other medical authorities contend that 90 mg only starts to meet our biological needs. Recent studies at the National Institutes of Health have found that a dose of 150 mg to 200 mg is optimal for raising the vitamin to full capacity in the bloodstream of healthy, nonsmoking adults. Above that, researchers contend, people simply excrete the rest in what is sometimes referred to as “expensive urine.”

The natural health community generally suggests much higher doses, in part because it recognizes that most of us aren’t as healthy as the 22-year-old men in the studies. At the high end of the spectrum is Owen Fonorow, who in 1995 co-founded the Vitamin C Foundation in Texas. Fonorow sticks by Pauling’s recommendation of 3 gm per day for healthy adults, although he, like Pauling, routinely takes 18 grams. Fonorow says the federal recommendations are aimed at the wrong target. “Everybody agrees [the USRDA has] done a good job eliminating clinical scurvy,” he says. “Where it’s missed the boat is determining the optimal level of vitamin C for good health.”

Many health advisers and scientists operate in the middle ground between the government’s 90 mg and Pauling’s 18,000 mg. The Linus Pauling Institute recommends that healthy adults consume at least 200 mg each day of vitamin C. Interestingly for a foundation named for a man who consumed 90 times this amount on a daily basis, the Institute says that 200 mg can be provided by five servings of most fruits and vegetables, and recommends additional supplementation only for vitamin E, selenium, and, in some cases, calcium.

Many alternative-thinking scientists now frequently recommend a range of 500 mg to 1,000 mg per day—preferably in two or three doses with meals. But that’s when you’re healthy. While studies do not prove that vitamin C prevents the common cold, scientists have found that large doses taken at the onset of a cold can shorten its duration by 23 percent, on average. Those studies recommend taking between 1,000 mg and 8,000 mg daily at the first signs of a cold, in doses of up to 1,000 mg a piece. With regard to cancer, Riordan’s research indicates that some cancer patients are approaching clinical scurvy (a side effect of chemotherapy treatments), and therefore need far higher doses. A common recommendation is 20,000 mg of oral vitamin C supplements per day for cancer patients, or whatever their bodies can handle.

How Much Is Too Much?

In the estimated 20,000 studies conducted on vitamin C over the last six decades, there are no indications that higher doses are toxic. An excess simply produces diarrhea.

“There are some people who, when they’re sick, can take orders of magnitude more than 3 grams per day with no intolerance,” says Fonorow. He follows the bowel tolerance guidelines codified by Dr. Cathcart: Keep taking approximately a gram every hour until you have to go to the bathroom—at which point you’ve reached your limit.

“If you’ve got diarrhea, you’ve gotten too much,” says Fonorow. “What you’re trying to figure out is, whether this is a 30-gram cold or a 100-gram cold. If you take 100 grams for a 30-gram cold, you’ll be on the pot all day.”

People do need to be aware that if they have been taking large doses of vitamin C to ward off a cold or to fight a serious illness, they should avoid going abruptly from, say, 8 grams a day down to one gram. This can cause what is called the “rebound effect,” leading to symptoms of scurvy. It is thus important for people to wean themselves off megadoses gradually by reducing the amount they’re taking over a period of a week or so.

While there are serious unresolved controversies among experts as to how much and what kind of vitamin C to take, there is no disagreement that an adequate supply of vitamin C is essential to good health. But this begs the question: If vitamin C is so critical to our daily body functions, why don’t our bodies make it naturally? Interestingly, most animals, except guinea pigs and primates, do. Animals produce it naturally in the liver, in quantities proportionate to body weight—the equivalent for a human of 10 to 12 grams per day when healthy and 5 to 10 times or more than that when stressed. But humans lack the enzyme to turn glucose into vitamin C. In the 1960s, Irwin Stone, PhD, developed the theory that some 65 million years ago, our tropical ancestors ate enough fruits and leafy vegetables that were high in vitamin C that we “successfully” mutated away from producing it. This was actually an evolutionary advantage while we lived in trees and gorged on fruit—our bodies were relieved of the necessity of turning glucose into ascorbic acid. But it has turned into a disaster now that we live in a polluted world, eating diets low in C. Stone, and others, view vitamin C supplementation not as simply a matter of addressing an accidental dietary deficiency, but of attempting to correct a species-wide genetic defect that has a most profound impact on our health.

Why do we need vitamin C?

Vitamin C in any of its natural forms is believed to be involved in more biochemical reactions in the body than any other vitamin. In his book, Vitamin C: Its Molecular Biology and Medical Potential, Sherry Lewin, PhD, says that vitamin C is necessary for some 300 functions in the body. It protects the cardiovascular system and prevents heart disease, balances cholesterol levels and plays an important role in the body’s production of collagen. As the protein constituent of our connective tissue, collagen literally holds us together—maintaining our skin, muscles, bones, and blood vessels—and aids in the healing of wounds. Vitamin C is necessary for the operation of our immune systems; our white blood cells cannot function properly without an adequate supply. Vitamin C also plays a key role in the synthesis of neurotransmitters, steroid hormones and metal ion metabolism. It is most widely known, however, as an antioxidant—preventing and repairing cellular damage caused by toxic metabolic byproducts that many 
scientists think are the major cause of many diseases and aging.

Beets vs. Corn

For many years, the only source of vitamin C was food or a synthetic vitamin derived from corn sugar. Recently, though, beet-derived C has caused a buzz in the alternative health community. Critics of beet superiority point out that laboratory analysis shows no difference in structure or action between the two, and that all previous studies on the benefits of vitamin C used corn-derived products. However, a number of well-known MDs, including W. Lee Cowden and Douglas Brodie, say they see better results using beet-derived vitamin C for their intravenous use in cancer therapies. With that in mind, some vitamin suppliers, including NutriCology, specify which forms of their vitamin C are derived from beets and which are from corn.


By Kristen Bole

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