by Steve Hickey
Dr. Pauling’s contribution is crucial to the story of vitamin C. Strangely, his starting point was to claim that vitamin C could prevent and treat the common cold. From here, he went on to argue that all infectious diseases could be helped with the vitamin: high-dose vitamin C could be considered analogous to an antibiotic, but it would work on viruses as well as bacteria, and would strengthen the immune system. Going further, he claimed that all disease could be helped by vitamin C. Atherosclerosis, the underlying cause of heart disease and stroke, he explained, was caused by vitamin C deficiency. Finally, Dr. Pauling stated that cancer patients would live far longer, or might even be cured, with a sufficient intake of vitamin C.
Since such claims are far beyond the day-to-day experience of most physicians, it is hardly surprising that the medical profession thought Dr. Pauling had lost his way. These ideas, however, did not begin with him—several independent scientists and physicians had witnessed the remarkable properties of vitamin C. Dr. Pauling’s contribution was to place these observations within an evolutionary context and to stake his scientific reputation on vitamin C.
The Case for High Vitamin Doses
Dr. Pauling considered how animals use vitamin C. Animals that synthesize vitamin C make relatively large amounts; for example, rats reportedly make 70 mg per kilogram of body weight each day. If a rat is stressed, the amount of ascorbate it produces increases, to about 215 mg per day.57 However, this is insufficient to maintain vitamin C levels in sick animals, and as blood levels fall, urinary excretion increases by a factor of ten.58 An injection of vitamin C—a dose roughly equivalent to about 5 grams (5,000 mg) in a human—restores the plasma ascorbate level, blood pressure, and capillary perfusion to normal, while inhibiting bacterial growth. Other animals also increase their vitamin C production when stressed.59 A plausible explanation is that sick animals increase both the manufacture of vitamin C and its excretion. The rate of ascorbic acid production in the rat is equivalent to a dose of between 5 grams and 15 grams per day, given intravenously, to a 154-pound (70 kg) adult human. Similar rates of production are found in goats and other animals. Domesticated cats and dogs produce somewhat less (human equivalent, 2.5 grams). By way of comparison, the RDA in the United States is less than 0.1 gram per day, between 50 and 150 times lower. Furthermore, oral vitamin C is only partly absorbed.
A direct comparison between the amounts required by animals and humans could be misleading. Humans might have evolved to need less, for example. Dr. Pauling used an evolutionary argument and estimated that the amount of vitamin C in 110 raw plant foods, supplying 2,500 calories, is at least thirty-five times the RDA. However, there is little data on the diet of early man or other mammals. While it is likely that plants 40 million years ago had similar levels of vitamin C to those we find today, we do not have direct measurements. Our ancestors may have been largely vegetarian, though we cannot be certain about this.
Animals that do not synthesize vitamin C may eat a vegetarian diet, providing a high level of the vitamin. However, we cannot be sure that this is always the case, as we do not have a complete list of such animals. We do know that primates, other than humans, consume large amounts of vitamin C in their mainly vegetarian diet. A pet or laboratory monkey is assumed to need the equivalent of 1 gram of vitamin C per day, far more than governments recommend for humans. A wild gorilla eats vegetation containing about 4.5 grams of vitamin C each day. Despite these reservations, Dr. Pauling assumed a diet similar to that of the great apes and calculated the early human intake of vitamin C as somewhere between 2.3 grams and 9.5 grams per day.60 He suggested that unless it could be shown that our biochemistry is substantially different from our nearest animal relatives, humans should probably be consuming gram-level doses of vitamin C, every day.
Dr. Pauling became convinced that there was a scientific case for high doses of vitamin after listening to Dr. Irwin Stone’s ideas. According to Dr. Stone, people need vitamin C in large quantities to deal adequately with infection and stress. Drs. Stone and Pauling thought vitamin C, as ascorbic acid, is required in the diet because of an identifiable genetic mutation, which could be classed as an inborn error of metabolism.
“The Vitamin C Man”
A small number of nutritionists do not regard ascorbic acid to be vitamin C, but instead talk of a “vitamin C complex.” There is no supporting evidence for this approach, as L-ascorbic acid given alone will both prevent and cure scurvy. The finding of explanations in the simplest possible form is a central part of the scientific method. Occam’s razor, from William of Ockham in the fourteenth century, is applied to both philosophy and science: Put simply, it states that all things being equal, the simplest explanation is preferred. Suggestions that vitamin C is some ill-defined mixture of natural substances is unscientific, although it may be profitable to the commercial organizations concerned.
People consuming the low RDA levels of vitamin C may be considered deficient. Authorities who claim that we only need such small amounts should be required to provide solid data to show that low doses are optimal. Unless such data is produced, official advice may be subjecting millions of people to unnecessary ill health.61 There is a bias at the heart of conventional nutritional advice. The original hypothesis for a vitamin was that it was a substance required in small amounts to maintain good health. This definition has carried through into modern medicine and it has come to be regarded as fact. People have forgotten that the idea that vitamins were needed in only small amounts was a relative measure, comparing the amount of vitamins to the proportion of fat, protein, and carbohydrate in typical foods. We are now in the unfortunate position where the idea has become a medical dogma.
For decades, it was assumed (without any supporting evidence) that acute scurvy was the only vitamin C deficiency disease. The idea that long-term deficiency could result in chronic illnesses, such as cataracts, heart disease, or arthritis, was largely ignored because there was no “proof” for this suggestion. Dr. Pauling argued for an increased requirement for vitamin C, using comparative biochemistry and evolutionary data. He believed that people had enough vitamin C in the diet to prevent them dying or becoming sick from acute scurvy, but insufficient to prevent disease in the longer term.
Linus Pauling brought the claims for high-doses of vitamin C to the public and named a new form of nutritional therapy—orthomolecular medicine. After a stellar career as one of the greatest scientists ever, he was happy to be known as “the vitamin C man.”
These and other scientists and medical doctors have fought over the decades to make a case for high doses of vitamin C to fight disease. While they remained marginalized by the conventional medical community, their courageous struggle has brought the many benefits of vitamin C to the attention to a wider public and, in the process, saved many from needless suffering.
CHAPTER 3
Taking Vitamin C
“What makes ascorbate truly unique is that very large amounts can act as a non-rate-limited antioxidant free radical scavenger.”
—ROBERT F. CATHCART III
Many nutritionists refer to the Recommended Dietary Allowance (RDA) by an alternative name—“ridiculous dietary allowance.”1 The rationale behind the official RDA for vitamin C is the prevention of acute scurvy, but it ignores the mounting evidence that higher doses provide more optimal health. A general assumption used in deriving the RDA was that people’s individual requirements do not vary greatly. Thus, the RDA does not cover the needs of the sick, the elderly, or others who may need far greater amounts. Having sufficient vitamin C to prevent acute scurvy means that collagen synthesis is sufficient to provide the body with a minimal structural integrity. However, this level of intake, which prevents sickness and death in the short term, has little relevance to the question of the optimal intake for disease prevention. People consuming RDA levels may be endangering their well-being, and even their lives, because of a chronically deficient intake of vitamin C.
The core dispute that has made vitami
n C so controversial over the years concerns the optimal intake. Scientists have been unsure how much a person needs for the greatest health benefits. Fortunately, recent research has thrown light on this dark corner of nutrition. One confounding factor is that each person is biologically unique. It may be impossible to specify a single intake to cover the needs of a large population. A second factor is the age and state of health of the individual. Some healthy people might tolerate only a couple of grams (2,000 mg) of vitamin C but, when physiologically stressed, that tolerance might increase 50-fold, or even 100-fold.
Errors in Determining the RDA
A few milligrams a day of vitamin C will prevent acute scurvy. In the short term, a person consuming this small amount will not become ill or die through scurvy. This fact forms the basis of the argument that humans need only a few milligrams a day for good health. Since prevention of the deficiency disease requires only micronutrient amounts of ascorbate, it was classified as vitamin C.
At the time, there was no convincing evidence to show that doses higher than milligram levels were needed. In the 1990s, Mark Levine, M.D., at the U.S. National Institutes of Health (NIH) showed that a healthy adult taking less than about 200 mg of vitamin C each day would have a deficient blood level. By giving varied doses to medical student volunteers, Dr. Levine was able to show that the body attempts to maintain a minimum level in the blood (the body retains 60–80 μM/L in blood plasma). If the intake falls below this level, molecular pumps in the kidney reabsorb vitamin C to prevent loss in urine. These pumps are highly effective: it takes between one and six weeks without vitamin C to reduce the blood concentration to half its original value. These pumps are essential to prevent acute scurvy in times of vitamin C shortage.
The NIH stated that these levels of retention in the blood suggest a required intake of about 200 mg of vitamin C per day. As well as blood plasma levels, Dr. Levine also measured the vitamin C in white blood cells. These cells have molecular pumps in their outer membranes, which are similar to those in the kidney. A white blood cell can accumulate a higher level of vitamin C than the surrounding plasma by actively absorbing the molecule. Dr. Levine found that white blood cells were less sensitive than plasma to intakes of vitamin C. Indeed, compared to plasma, white blood cells need only about half the vitamin C intake (100 mg) to reach their anti-scurvy retention level. This level was used for the RDA and, superficially at least, it appeared to be a rational basis for the new value. However, we need to examine the issue further.
The body has two lines of defense against scurvy. First, the kidney pumps retain a minimum level of vitamin C in the body. However, some tissues, such as brain, adrenal glands, and white blood cells, are more sensitive to vitamin C loss. These cells, which have a specific and essential requirement for vitamin C, have special vitamin C pumps that allow them to preserve higher levels than other tissues. In times of shortage, these tissues maintain their high internal concentrations, whereas blood plasma and less sensitive tissues become deficient. As a person loses vitamin C, most of their body tissues become deficient, though the critical cells and tissues that need it most are protected. Only late in the illness will these essential tissues become greatly deficient. By this time, the person will be suffering severe symptoms and will be close to death.
The use of specialized tissues such as white blood cells for determining the RDA is a gross error.2 In a person consuming these recommended low intakes of vitamin C per day, the majority of tissues may be deficient. Indeed, the plasma level could often fall below the threshold levels sustained by the kidneys. Had Dr. Levine used red instead of white blood cells, the recommendations would have been completely different. Red blood cells are more numerous than white cells and are not specialized in their use of vitamin C. Red blood cells do not become “saturated” with vitamin C at daily intakes of 100 mg, but would continue to absorb the vitamin at much higher intake levels. Red blood cells are affected by scurvy sooner than white cells. They provide a more appropriate estimate for the RDA, as they are similar to the majority of the body’s tissues. A dietary allowance based on red blood cells would prevent earlier signs of scurvy. If scientists need an easily obtainable tissue to determine the optimal human intake, red blood cells would be more suitable than white cells.
Risk-Averse Experts
For over fifty years, governments have felt it necessary to provide nutritional guidance to their populations. Unfortunately, they possessed insufficient data to make a considered argument for many of the nutrients, especially vitamin C. Governments are not particularly good at admitting ignorance and typically select their committees from scientists who support the status quo. Furthermore, scientists on such committees may feel that they are required to be conservative. Rather than making an objective assessment of potential health benefits, committee members may think they are steering on the side of safety by recommending an intake that is as low as possible without an individual being at risk of acute scurvy.
By recommending a minimal dose, governments risk specifying a grossly inadequate intake. Healthy people who consume just a few milligrams a day will not die or suffer the acute effects of scurvy. At intakes of 40–60 mg per day, specialized tissues such as brain and white blood cells may maintain high internal levels. Thus, government scientists in the United Kingdom, being suitably conservative, set the Dietary Reference Intake (DRI) for adults at 40 mg per day.3 Their aim was presumably to use the precautionary principle in order to avoid people being poisoned by higher doses. (There is no evidence for such effects from vitamin C, however.) The U.S. Food and Nutrition Board also based their RDA on the amount needed to prevent acute scurvy. The RDAs exclude people with special needs, which may be anyone who is elderly, ill, or stressed. However, they are applied generally to the whole population.
The official aim of the RDA or DRI is to recommend the intake with minimum risk of inadequacy and toxicity. Since there is remarkably little danger from high doses of vitamin C, we might expect the data for the recommended intake to be strongly influenced by potential beneficial effects. However, in the bizarre world of bureaucratic logic, beneficial effects are often excluded from the analysis of requirements. Instead of a well-founded approach based on the available data, the recommendations are essentially based on risk analysis. Risk analysis is useful for the dangers of toxic substances in the environment, but is inadequate when considering a substance essential to life. Such recommendations are biased against higher doses, because theoretically they could always be dangerous in some unspecified way.
Science and common sense suggests that a single RDA for vitamin C, or any other vitamin, is unlikely to be adequate for the population. Humans are biologically diverse and such biodiversity implies some people would need far more than the recommended doses. This variation in requirements can also occur within a single individual, as needs may change with illness or age.
Government values do not consider long-term effects of deprivation, although even intakes several times the RDA might be associated with chronic disease. For example, atherosclerosis and heart disease could be a result of chronic subclinical scurvy.4 Governments have no evidence that chronic disease is not a result of their low recommendations. Investigating the long-term effects of vitamin C deprivation is difficult and expensive. Without this evidence, the recommendations rely on the opinions of experts. Yet, if subclinical scurvy causes chronic disease, we will all suffer the consequences of doses that are too low. If governments would admit the level of uncertainty in their recommendations, people would at least be able to reach their own conclusions.
Factors Affecting Vitamin C Absorption
Dr. Levine hoped to solve the problem of vitamin C requirements using biochemistry. He suggested that vitamin C requirements could be found by experiment.5 His idea was to estimate the optimal intake by finding out how much of a dose is absorbed or excreted—someone who is taking in too much vitamin C might not absorb it or might excrete it rapidly.
At that time, scient
ists knew little about how doses of vitamin C traveled around the body. There was some information for healthy, young adults, in whom vitamin C is actively absorbed from the intestine.6 Almost all of a low dose, below about 60 mg, is absorbed.7 The absolute amount absorbed increases with dose, but only slowly: up to 80–90 percent of a single 180-mg dose is absorbed, reducing to 75 percent at 1 gram, 50 percent at 1.5 grams, 26 percent at 6 grams, and 16 percent at 12 grams.8 Only 2 grams of a single 12-gram dose would be absorbed, providing a limit to the intake possible from a single dose. Conversely, only small amounts of low doses are excreted unchanged. As the dose increases, more vitamin C is excreted because the pumps in the kidney are limited in the amount that they can retain.
The NIH proposed an RDA of 200 mg of vitamin C per day for healthy young men. A little later, Dr. Levine obtained similar results for healthy young women. In a series of influential papers, he described the absorption, blood levels, and excretion of vitamin C.9 These papers form the core evidence used for current government recommendations. The NIH suggested that the body was “saturated” at an intake of 200 mg per day. According to this notion, increasing the dose would not sustain blood levels at a higher value than 60–70 μM/L and the majority of larger doses is not absorbed from the gut. This is clearly an error, as sustained blood levels of at least three times this claimed maximum concentration are achievable with repeated oral doses.
As mentioned previously, vitamin C is not confined to the blood plasma, but is selectively pumped into a number of specialized tissues, including the brain, white blood cells, and the adrenal glands.10 The cells and organs that are protected in this way are essential to survival and have higher than normal requirements for vitamin C and its antioxidant protection. White blood cells, for example, have specific requirements for vitamin C in fighting infection. These white cells have a short lifespan and their death is controlled by levels of antioxidants.11 The pumps in these tissues ensure that in times of shortage, the vitamin C levels remain high.