by Steve Hickey
The margin of safety for large doses of vitamin C is much greater than that for aspirin, antihistamines, antibiotics, pain medications, muscle relaxants, tranquillizers, sedatives, and diuretics. In other words, vitamin C is far safer than commonly used drugs. However, harmful effects have been wrongly attributed to vitamin C, including hypoglycemia, rebound scurvy, infertility, mutagenesis, and destruction of vitamin B12.28 We have not found a single validated report of a healthy person dying from a vitamin C overdose in the scientific literature. Not one.
As Safe as Milk
Vitamin C is generally recognized as safe (GRAS). This means that U.S. Food and Drug Administration (FDA) experts consider it can be safely added to food and cosmetics. In the case of food, this is a sensible approach, as without it we would die. Nevertheless, too much vitamin C, like an overdose of water, could be harmful. Taken in excess, water can lower the concentration of sodium in the blood and cause the brain to swell. To put the safety of vitamin C in context, we consider that it might be easier to commit suicide by overdosing on pure water than by eating too much vitamin C.
A review of twenty-three years of U.S. poison control center reports, from 1983 to 2005, indicates that vitamins have been connected with the deaths of only ten people. Indeed, poison control statistics confirm that more Americans die each year from eating soap than from taking vitamins.29 Even including intentional and accidental misuse, the number of alleged vitamin fatalities is strikingly low, averaging less than one death per year for more than two decades. The American Association of Poison Control Centers (AAPCC), which maintains the U.S. database of information from sixty-one poison control centers, has noted that vitamins are among the most reported substances. The small number of fatalities does not, therefore, reflect a lack of reporting. In sixteen of twenty-three years, the AAPCC reported that there was not a single death due to vitamins.
These statistics specifically include vitamin A, niacin (B3), pyridoxine (B6), other B-complex vitamins, vitamins C, D, E, other vitamins such as vitamin K, and multiple vitamins without iron. Minerals, which are chemically and nutritionally different from vitamins, also have an excellent safety record, but not quite as good as vitamins. On the average, one or two fatalities per year are typically attributed to iron poisoning from gross overdosing on supplemental iron. Deaths attributed to other supplemental minerals are very rare. Even iron, although not as safe as vitamins, accounts for fewer deaths than laundry and dishwashing detergents.
The occurrence of even one death should be taken seriously. However, the background details of these reported events are not provided. A human death from an oral overdose of vitamin C in a healthy person does not appear to have been established in the literature. Moreover, a brief consideration of some medical mortality figures places this into context.
Let us consider just those deaths and injuries caused by the effect of aspirin-like drugs (nonsteroidal anti-inflammatory drugs or NSAIDs) on ulcers in older people alone. Note that this is a rather severe restriction in terms of stomach effects and it excludes other age groups. These drugs are often also used for slight headache, muscle strain, and arthritis. Every year, about 41,000 older adults are hospitalized in the U.S. The average stay in the hospital for peptic ulcer in elderly persons is over a week (8.5 days), but about 350,000 unnecessary days in the hospital occurred in 1987 due to NSAIDs.30 In fact, 3,300 people die every year from these complications.31 These figures are a challenge to anyone who claims high doses of vitamin C are a health risk. Furthermore, they are only a small fraction of the large number of unnecessary deaths each year from prescription and over-the-counter drugs.
Vitamin C is one of the least toxic substances known. There have been one or two allegations, but nothing confirmed about alleged deaths from vitamin C. The acute safety of a drug is described by the therapeutic index—the toxic dose divided by the therapeutic dose. The Lethal Dose 50 (LD50) is the dose at which 50 percent of the subjects would die. For example, a substance with a therapeutic dose of 1 gram, and an LD50 of 2 grams, would have a therapeutic index of 2. Such a low therapeutic index indicates a dangerous drug, with little margin of safety. This kind of drug would be suitable for treatment in only the most severe, life-threatening conditions. The therapeutic index of vitamin C for a 154-pound (70 kg) person taking 1 gram is at least 350, which indicates a high degree of safety. A person who ate a half-pound of vitamin C (227 grams) at a single sitting would probably have trouble with stomach acidity and diarrhea. However, they would be likely to survive.
By way of comparison, the widely available painkiller paracetamol (acetaminophen) has a therapeutic index of about 25. The recommended dose of paracetamol is 1 gram and doses as low as 4 grams can cause serious liver damage.32 In the U.S., paracetamol overdoses cause about 56,000 emergency room visits and 26,000 hospitalizations each year.33 Paracetamol causes 458 deaths in these patients each year, many from unintentional overdoses.
At least 16,500 people die each year in the U.S. because of over-the-counter painkillers, and over 100,000 may be hospitalized by their side effects.34 Medical error is a leading cause of death, reportedly killing at least 100,000 people a year in the U.S.35 In addition, 12,000 cases of unnecessary surgery, 7,000 errors in giving drugs, 80,000 hospital infections, 106,000 adverse drug reactions, and 20,000 other errors, all lead to avoidable death.36
The media give high prominence to vitamin C scare stories, based on little evidence. They often fail to highlight more substantial medical facts, if such information could disturb the status quo.
Potential Side Effects
Does Vitamin C Cause Kidney Stones?
There is no evidence of adverse effects from large amounts of vitamin C.37 One of the most frequent scare stories is the idea that vitamin C causes kidney stones. Although this originally may have seemed a plausible hypothesis, in practice, high rates of kidney stones are not found in people taking large amounts of vitamin C. Vitamin C has even been proposed and used as a treatment for kidney stones.38
The main argument for increased kidney stones relates to those stones formed from calcium oxalate. Unlike some other stone types, these can form in acidic urine, and vitamin C is a weak acid. Calcium oxalate stones make up about three-quarters of all kidney stones. Excess calcium in the urine promotes calcium oxalate stone formation and magnesium inhibits it.39 High carbohydrate intakes can also increase excretion of calcium.40 Some researchers have claimed that vitamin C increases the excretion of oxalate in the body slightly, but other studies show no increase in oxalate excretion.41 It now appears that the higher oxalate levels in some studies are a result of inadequate preservation of samples.
There is a more fundamental problem with these studies of urinary oxalate and calcium. Researchers generated a means of estimating the risk of calcium oxalate formation from the chemical composition of urine.42 However, this model does not include the effect of vitamin C: the presence of vitamin C in the urine, as expected with high intakes, would lower the risk estimate. The theoretical connection between ascorbate and oxalate stones is based on the Tiselius equation, which relates stone risk to calcium and oxalate and inversely to magnesium. It does not directly include vitamin C. The true situation is that large doses increase ascorbate in urine and this would lower the risk by binding calcium. It is strange indeed that the base argument for vitamin C–associated risk excludes the molecule in question from the analysis. If you include ascorbate at high concentration, the result would be a lower risk of oxalate stones! Thus, many doctors have overestimated the dangers of high-dose vitamin C, which could be protective.
There are additional reasons to suspect that vitamin C may protect against kidney stones. For example, in high doses, it increases urine flow: fast moving rivers deposit little silt. Furthermore, kidney stones appear to form around a nucleus of infection and, since vitamin C at high concentrations is bactericidal, it may remove the focus for stone formation.
Epidemiological evidence suggests vitamin C does not increase k
idney stones. A 14-year prospective study of 85,557 women revealed no evidence that vitamin C causes kidney stones.43 People taking less than 250 milligrams per day and those taking 1.5 grams or more had similar rates of kidney stones. An earlier study of 45,251 men suggested that those taking more than 1.5 grams of vitamin C per day had a lower risk of kidney stones.44
There are other, less frequent, types of kidney stones, such as those composed of calcium phosphate and struvite (magnesium ammonium phosphate), which can occur in infected urine but which dissolve in acid. Acid urine is produced by vitamin C, which once again may be preventive. Vitamin C is not directly involved in the formation of uric acid stones, found in gout, or cystine stones in children.
Other Side Effects?
There may be interactions with vitamin C in some enzyme deficiencies. In glycogen storage disease (type 1), also known as von Gierke disease, excess glucose is stored in the body as glycogen, from which it can normally be released quickly. This disease sometimes arises from an inherited deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD). Some authors claim that this is the most common enzyme deficiency in humans, affecting over 400 million persons worldwide.45 However, the deficiency disease is actually rare, with an incidence of 1 in 100,000 births in the U.S. Since the gene is sex linked and located on the X chromosome, the deficiency is rare in females. The problem occurs more frequently among people of Mediterranean, African, and Southeast-Asian descent. The incidence in non-Ashkenazi Jews from North Africa may be as high as one case in 5,420 people. The low incidence of clinical enzyme deficiency disease indicates that the condition is rather less common than is normally suggested.
People with G6PD deficiency can suffer glycogen storage disease. Before therapies, such as continuous feeding and the use of cooked cornstarch, most people with this rare condition died young. With improved treatments, more patients are living to adulthood. Even with treatment, people with this disorder have short stature and enlarged livers. Often they suffer from gouty arthritis with kidney stones, increased blood fats, hypertension, acute pancreatitis, osteoporosis, and increased bone fractures.
It has been suggested that a person with this enzyme deficiency who takes high-dose vitamin C supplements could be subject to hemolytic anemia.46 There is some evidence for this claim in newborn infants, and occasional anecdotal reports in adults.47 But claims for this side effect have been extrapolated to the extreme and G6PD deficiency causes little risk to healthy people considering high-dose vitamin C.48
People suffering from hemochromatosis, or iron overload disease, are claimed to show side effects with high-dose vitamin C. In apparently healthy individuals, vitamin C does not cause excess absorption of iron.49 However, hereditary hemochromatosis affects about one in 300 people of northern European descent.50 People with this disease could be adversely affected by long-term ingestion of large doses of vitamin C, although this risk has not been clearly established.51 There have been one or two case reports of people with hemochromatosis suffering problems with high doses of vitamin C, but considering the large number of supplement takers these reports could simply reflect a chance association. High blood levels of vitamin C in normal, healthy adults and preterm infants, in the presence of iron, do not appear to cause damaging oxidation. Supplementing with vitamin C may prevent such damage, even in iron-overloaded plasma.52
These objections to the use of vitamin C have been overstated. Dr. Cathcart, who was one of the most experienced physicians with high-dose vitamin C supplementation, reports direct experience of two patients with hemochromatosis, whom he treated with massive doses of ascorbate without problem. In the thousands of patients he has treated, he has never seen any evidence of a damaging iron-related reaction. His clinical experience indicates that vitamin C increases iron absorption when the body needs it, and he suggests that vitamin C may also increase excretion of iron when there is an excess. He proposes that the vitamin in sufficiently high doses might be an effective treatment for hemochromatosis, which is caused by free radical reactions. The chemistry of vitamin C acting either as an oxidant or as an antioxidant in such conditions is not well understood. While some scientists suggest theoretical problems, others propose beneficial effects. In Dr. Cathcart’s words: “This theoretical difficulty concerning C is typical of how the orthodoxy will expand a theory into a fact without any evidence.”53
The Precautionary Principle
For decades, the medical establishment has accepted the idea that we only need low doses of vitamin C for optimal health. Despite the fact that this idea has little, if any, scientific support, it is now promoted by medical and health organizations worldwide. It is therefore deemed necessary to provide scientific evidence for the alternative hypothesis, that people need high doses. This may be absurd, but it is based on the precautionary principle, which states that a policy should not be implemented unless there is a scientific consensus that it would cause no harm to the public.54 The burden of “proof” falls on those who advocate the change. A company wanting to release a chemical into the environment, for example, needs to provide solid evidence that it will do no harm. In the case of a potentially harmful new chemical, such an argument is conservative and is based on appropriate caution.
A standard criticism of the precautionary principle is that it only applies to new ideas. In fact, existing procedures may be equally harmful, if not more so. In effect, the precautionary principle states that even if there is no evidence for a side effect, we should still act as though the side effect is possible. Following this principle, you assume the worst case will occur if too large an intake of vitamin C is recommended, and set the guidelines at a minimum level. For radiation, potentially harmful environmental chemicals, and synthetic drugs, this may be conservative. However, when considering nutrients that we cannot live without and are ignorant of how much a person needs for good health, the approach is inappropriate. In the case of vitamin C, the precautionary principle is being misapplied, as there is no evidence that low intakes of vitamin C are less harmful than higher intakes.
When “Side Effects” are Useful
Scientists agree on only one “side effect” for high doses of vitamin C—a single, large dose of vitamin C can be used as a natural laxative. It provides an alternative to drug-based remedies for constipation. At high doses, diarrhea can occur, although the dose needed to produce the effect varies. The level at which diarrhea occurs is called the “bowel tolerance” level and is an indicator of the body’s need for supplementation. When a person is sick, the bowel tolerance can increase by a factor of 100 times. So, a person with influenza, who in normal health would tolerate 2 grams a day, might consume 200 grams (200,000 mg) without any discomfort.
Strangely, the medical establishment classes the action of vitamin C on the bowel as an adverse side effect, but ignores the massive increase in bowel tolerance in the sick. Implausibly, a maximum recommended intake level has been set based on the smallest dose that might cause loose stools in some people. Given this, it is surprising that there are no government maximum recommended intakes for high-fiber foods such as beans. The U.S. Institute of Medicine had apparently decided that the intake of vitamin C must be limited, but could find no other side effects of large doses of vitamin C in healthy people. They set the maximum intake at 2 grams of vitamin C per day, as at this level almost no one in the population will suffer from diarrhea. Presumably, people have insufficient common sense to notice diarrhea and reduce their own intake. Despite several decades of attempts to find a reason why taking high doses of vitamin C could be harmful, detractors have not found toxicity simply because it does not exist.
CHAPTER 4
Conventional Medicine vs. Vitamin C
“A wealth of information creates a poverty of attention.”
—HERBERT SIMON, COMPUTERS, COMMUNICATIONS AND THE PUBLIC INTEREST
Limitations of Social Medicine
The use of social medicine to investigate the actions and properties of vitamin C
has inflamed and prolonged the controversy. To investigate heart disease, epidemiologists might look at how many people have heart attacks and determine the characteristics of people who are prone to the disease—for example, middle aged, overweight men, who smoke and eat junk food low in vitamin C. An epidemiologist can then determine the factors, such as environment, job hazards, family patterns, and personal habits that are more prevalent in people with coronary thrombosis. However, what epidemiology lacks is a high degree of explanatory power. To explain how a heart attack happens requires physics, biochemistry, and physiology. Without a grounding in these basics, epidemiology can degenerate into what some people have described as pseudoscience.1
An awareness of the limitations of epidemiology gives some perspective when considering the conflicting nutritional advice for good health, such as the requirements for vitamin C. According to popular myth, epidemiology “proved” that smoking causes lung cancer. Population studies certainly alerted scientists to the link between smoking and lung cancer, but this may have given an incorrect impression of the power of the statistical approach. A number of factors need to be in place before epidemiology can identify a potential causative agent.
We can be confident that cigarettes cause lung cancer, but epidemiology played only a small part in the justification. Most importantly, we have a detailed scientific explanation of how smoking causes lung cancer. Burning tobacco releases chemicals that cause genetic mutations, chromosome damage, irritation, and proliferation of cells, as well as oxidation of vitamin C.2 The act of smoking delivers cancer-forming chemicals (carcinogens) to the delicate tissues of the lung and into the blood; they are found throughout the body tissues and are excreted in urine.3 These chemicals have been observed to promote cancer in animal models,4 although it can be difficult to reproduce the disease in healthy animals.5 However, if animals with spontaneous tumors are forced to smoke, they develop increased numbers of lung tumors.6 Thus, from our knowledge of basic pharmacology and biochemistry, the act of smoking can be predicted to increase the incidence of lung and other cancers.