by Steve Hickey
People visiting a physician expect to receive clear, unbiased information about what ails them and its treatments. More importantly, they need to know what they can do to prevent disease. Patients would like to have the information necessary to make informed choices, but in many cases, this information is not provided, and even doctors are often unable to evaluate the information they need to make decisions that are optimal for patients’ interests.19 People often disregard the advice of conventional experts and supplement their diet with gram-level doses of vitamin C and other antioxidants. Perhaps surprisingly, diverse groups of independent individuals can often produce more accurate solutions than those obtained by selected committees of experts.20 Thus, this popular decision could be a sign that medicine has gone astray and is refusing, unable, or unwilling, to respond rationally to the evidence.
Gram-level doses of vitamin C may prevent many diseases, but much higher doses are required for treatment of illness. The massive doses needed for therapy are often greeted with disbelief. When we inform doctors that 50–100 grams (50,000–100,000 mg) of vitamin C per day may be required to treat a common cold, their skepticism is transferred from the efficacy of the treatment to the size of the dose. Most clinical studies have considered doses of a single gram. A dose 100 times larger has very different properties.
One reason for the vitamin C controversy is contradictory clinical results from trials that used inadequate doses, doses that are 100 times too small and have consistently broken the basic rules of pharmacology.21 For an analogy, imagine a study in which 20,000 fertile young women are placed on the contraceptive pill to prevent pregnancy. The researchers want to show the pill has no effect, so they give one pill a month, instead of one a day, as designed. Control subjects take one sugar pill (placebo) per month. Now, suppose the results of this five-year trial indicate that, when taking a contraceptive pill once a month, the women became pregnant at the same rate as those on the sugar pill. No reasonable person would accept the claim that “the trial shows the pill does not prevent pregnancy.” You cannot expect a daily pill given monthly to have the same effect as the daily dose. However, this methodology is equivalent to studies of “high-dose” vitamin C, which have purported to show it is ineffective.
An optimal intake of vitamin C is the amount that prevents disease while minimizing the potential risk. It is a huge assumption to think that an intake to prevent acute scurvy will be adequate to prevent other diseases. Furthermore, there is substantial evidence that the intake of vitamin C needed to prevent chronic illness is much greater than the RDA. Unfortunately, direct studies on chronic disease and high-dose vitamin C intakes have not been undertaken, so we have to base our conclusions on an insufficient knowledge base. Typically, prospective studies provide the most direct information. In a prospective study, vitamin C intake is estimated in large numbers of subjects, who are then tracked over time to see if they develop specific chronic diseases. Such studies are expensive and often imprecise. For example, the vitamin intake may be estimated by a questionnaire and approximated from typical proportions found in particular food items. People’s diets may change with time and content tables do not take account of specific items—fresh, organic carrots contain more vitamin C than those found in cans, for example. To get an accurate estimate of the optimal intake, it would be necessary for these studies to include intakes of vitamin C ranging from 50 mg up to at least 10,000 mg per day, and this has not been done. Some researchers suggest strangely that vitamin C from food is somehow more effective than the same molecule contained in supplements. However, an alternative explanation is that the methods used to estimate vitamin C intake from food have limited accuracy. Another possible explanation relates to the fact that we eat several times a day and vitamin C is released from food more gradually than from supplements.22
Scurvy
Many people connect the word scurvy with history lessons rather than modern day health. The British Admiralty finally, after a delay of fifty years, enacted James Lind’s 1747 finding that consumption of citrus fruit could prevent scurvy. In the intervening period, thousands of sailors died. Unfortunately for them, the cost of providing citrus fruit was greater than the cost of a press gang. Then, as now, economic considerations often took priority over science or people’s well-being.
People with acute scurvy eventually suffer bruising, bleeding into their joints causing swelling and severe pain, and loss of hair and teeth. These symptoms are, as we have explained, a result of collagen shortage. Earlier onset symptoms include fatigue, arising from the reduced ability to make carnitine, and susceptibility to stress because of lower levels of adrenaline and noradrenaline.
In developed countries, acute scurvy is rare, as consuming a few milligrams of vitamin C daily prevents the illness, while outbreaks of scurvy are more frequent in the Third World. However, even in developed areas, people with chronic illness, the infirm, elderly, and children can be at risk, and low blood levels of vitamin C are common.23 Chronic scurvy may arise if a person has sufficient vitamin C intake to prevent a painful death in the short-term, but not enough to keep them healthy.
Preventing Heart Disease and Stroke
Many prospective studies indicate that low intakes of vitamin C are associated with an increased risk of cardiovascular disease. Despite such studies not including an investigation of higher intakes, it was assumed wrongly that approximately 100 mg of vitamin C per day gives a maximum risk reduction. The first National Health and Nutrition Examination Study (NHANES I) estimated that the risk of death from cardiovascular diseases was 25 percent lower in women and 42 percent lower in men who supplemented with vitamin C.24 The average intake of supplemental vitamin C was 300 mg per day.25
A review of nine studies, covering 290,000 adults, found that those who supplemented with more than 700 mg of vitamin C per day had a 25 percent lower risk of heart disease. These subjects had apparently healthy cardiovascular systems at the start of the ten-year study.26 A study of over 85,000 female nurses over a period of sixteen years found that higher vitamin C intakes helped prevent heart disease.27 Once again, high intakes of vitamin C from supplements (average of 359 mg per day) were linked to a 27–28 percent reduction in risk of heart disease. Notably, nurses who did not take supplements did not benefit from this risk reduction.
Similar results have been obtained with vitamin C and stroke. One study covered a twenty-year observation period documenting 196 cases of stroke (including 109 infarctions and 54 hemorrhages). The subjects with the highest vitamin C blood levels had a 29 percent lower risk of stroke than those with the lowest levels.28 This study of a Japanese rural community followed 880 men and 1,241 women aged forty years and older who were initially free of stroke when examined in 1977. Not surprisingly, those people who ate vegetables nearly every day had a lower risk of stroke than those who ate them two days a week or less. Blood plasma levels of vitamin C increased with fruit and vegetable intakes. While it is possible that some other component of the fruit and vegetable intake contributed to the reported benefit, there is no evidence to support this suggestion. There is also no evidence that people who ate fruits and vegetables may have benefited from associated behaviors or lifestyle. A more scientific approach is to note that even the plasma levels in this study correspond to deficiency and were below the well-nourished baseline. One may wonder how low the incidence of stroke could have been had these subjects been provided with appropriate vitamin C supplementation.
As might be expected from such a blunt experimental procedure, some prospective epidemiological studies have not revealed a lower risk of cardiovascular disease with vitamin C supplement use.29 Taken as a whole, however, these results suggest that in order to lower heart attack risk, vitamin C intakes may need to be high enough to maintain the body pool.30 It is also possible that much higher intakes of vitamin C could effectively eradicate heart disease from the population.
Preventing Cancer
People generally accept that eating fruits and ve
getables reduces the risk of many types of cancer.31 Vegetables contain a large number of phytonutrients and other cancer-preventing substances, so it is not obvious how much of the benefit might be a result of increased vitamin C intake.
Higher daily intakes of vitamin C are associated with a reduced risk of cancer in many organs, including the mouth, neck, lungs, and the digestive tract (esophagus, stomach, and colon). In one study, men with an intake of more than 83 mg of vitamin C daily had a 64 percent lower risk of lung cancer compared with those with an intake of less than 63 mg per day. This study followed 870 people over twenty-five years.32 Studies have linked an increased vitamin C intake with a lower risk of stomach cancer. The ulcer-forming bacterium Helicobacter pylori is associated with increased risk of stomach cancer. Since this bacterium decreases the amount of vitamin C in stomach secretions, supplementation has been suggested as an adjunct to antibiotic therapy for ulcers.33
Most large surveys have found little association between breast cancer and the low intakes of vitamin C that are typically studied. However, in one study, overweight women with an average vitamin C intake of 110 mg each day were found to have a 39 percent lower risk of breast cancer compared to similar women with an intake of 31 mg a day.34 The Nurses’ Health Study also suggests an association between low levels of vitamin C and breast cancer. A 63 percent lower risk of breast cancer was found in premenopausal women with an average intake of 205 mg of vitamin C per day compared with similar women who consumed an average of 70 mg each day.35 These subjects had a family history of breast cancer. Unfortunately, once again, data on higher intakes of vitamin C (in the range 1,000 to 10,000 mg) are not available.
Viral Illnesses
Reported results of treatment with massive doses of vitamin C are almost without parallel in medical history. A classic example is the study by Frederick R. Klenner, M.D., on polio. Around 1950, Dr. Klenner claimed that he could cure polio in a few days using vitamin C. This was at a time before polio vaccination and often patients were paralyzed or died, but Dr. Klenner reported that none of his patients died or suffered paralysis.
A research group led by Dr. Jonathan Gould in the 1950s conducted a placebo-controlled trial of vitamin C as a treatment for polio.36 About seventy children were treated in the study; half the children were given vitamin C and the remainder a placebo. All the children given vitamin C recovered. However, in the placebo group, approximately 20 percent had residual impairment. Dr. Gould did not report his conclusions because the Salk vaccine for polio had just been announced and, at that time, there was great hope and expectancy for the benefits of vaccination. However, if the report was correct, these results with vitamin C are more fundamental.
Vitamin C may act as a general “antibiotic” against all forms of viral disease. People still die of polio and many cases have occurred because of the use of live polio vaccination.37 Researchers have not found any comparable treatment for the unfortunate individuals who contract polio or other viral diseases each year. Astoundingly, similar claims by reputable physicians for vitamin C treatment of a wide range of viral illnesses continued over the following half century without being subject to clinical testing.
Heavy Metal Toxicity
Heavy metal toxicity is a continuing problem. Lead has been a problem for humanity for thousands of years and, for a time, was thought to be responsible for the fall of the Roman Empire. One idea was that the toxic properties of lead pipes caused widespread mental deficits. It is more likely that such effects were small, but produced a loss of vigor and fitness relative to other competing civilizations.38 Lead pipes had been used for several centuries before the fall of Rome and continued to be used in England, for example, until they were gradually phased out in the twentieth century. The toxic effect was not strong enough to prevent the burst of intellectual activity leading to and propelling the Industrial Revolution.
Recent problems of heavy metal poisoning involve lead from car exhaust, aluminum in water, and mercury in fillings.39 We will use lead poisoning as an example of the protective role of vitamin C. This poisoning is occasionally seen in pregnant women, in whom it can induce abnormal growth and development of the fetus. Children chronically exposed to lead suffer behavioral problems and learning disabilities. In adults, lead toxicity can produce high blood pressure and kidney damage. In older men, higher blood vitamin C levels are associated with lower lead concentrations in the body. A study of lead levels in 747 elderly men showed that oral vitamin C intakes of less than 109 mg per day were linked to higher lead in blood and bone than those consuming 339 mg or more each day.40 This result was supported by a study of 19,578 people, which indicated that higher serum vitamin C levels were linked with significantly lower blood lead concentrations.41
The response of blood lead levels to moderate intakes of vitamin C can occur in a matter of weeks. A placebo-controlled study of the effects of vitamin C supplementation (1,000 mg daily) on blood lead concentrations in 75 adult male smokers measured significant reductions (81 percent) in lead levels within a month.42 Lower intakes (200 mg per day) did not affect blood lead concentrations.
Cataracts
Considering its role in protection from free radical damage, vitamin C might be predicted to prevent cataracts, one of the leading causes of visual impairment.43 Cataracts arise for a number of reasons, including long-term ultraviolet (UV) light exposure and other ionizing radiation. They are also associated with high glucose levels in diabetics, and increase in frequency and severity with age. The primary effect of cataracts is to denature (deform) certain proteins called crystallins in the lens of the eye.
More severe cataracts are linked with low vitamin C levels in the eye. Unsurprisingly, therefore, increased blood plasma levels of vitamin C are also associated with decreased severity of cataracts.44 Increased vitamin C intake associates with lower cataracts in some but not all studies, presumably because the doses were not frequent enough to consistently raise blood and eye levels.45 A trial of antioxidant supplementation, including vitamin C (500 mg), vitamin E (400 IU), and beta-carotene (15 mg), in 4,629 adults over six years found no effect on the development and progression of cataracts.46 Some possible reasons for this lack of effect are that the vitamin C dose was small and some participants were given copper, which interacts with vitamin C, causing oxidation. Also, the form of vitamin E used was synthetic dl-alpha-tocopherol, which is often used in studies but is less biologically active than natural, mixed tocotrienols and tocopherols.
At some stage, almost every chronic disease has been related to an insufficient intake of vitamin C. The scientific evidence available is sparse and it may take centuries to determine which chronic illnesses are related to a shortage of vitamin C. In the meantime, the optimal amount of vitamin C is a matter of continued debate. It is time that medical scientists realized that attacking and denigrating vitamin C and other nutritional therapies can no longer be tolerated. An open, scientific approach to vitamin C and other nutrients could offer major benefits to humanity.
CHAPTER 2
The Pioneers of Vitamin C Research
“The conventional view serves to protect us from the painful job of thinking.”
—JOHN KENNETH GALBRAITH
“Eat your fruits! Eat your greens! They are full of goodness,” our grandmothers used to say. The advice was excellent, as these foods include essential vitamins that, together with minerals and phytonutrients, help prevent disease and keep us healthy. Current nutritional advice to eat between five and nine helpings of fruit and vegetables is consistent with our grandmothers’ advice, but does not recognize that the science of nutrition has made rapid advances in recent decades. We can now isolate and identify the beneficial substances in food.
The Discovery of Vitamin C
The first vitamins were identified at the beginning of the twentieth century. Christiaan Eijkman and his collaborator, Gerrit Grijns, had shown that rice bran contained small amounts of a substance that prevents disease in chickens. Then, in
1906, British biochemist Sir Frederick Hopkins fed rats a diet of artificial milk, made from protein, fat, carbohydrates, and mineral salts. He found that they did not grow as expected. However, adding a little cow’s milk to their diet allowed the rats to develop rapidly. In order to grow, the rats clearly needed some additional substance in the milk.
In 1912, Dr. Hopkins and Casimir Funk proposed that the absence of sufficient amounts of certain substances in food causes disease. Their “vitamin hypothesis” suggested the existence of four vitamins that provided protection against four diseases:
• Vitamin B1, which prevents beriberi
• Vitamin B3, which prevents pellagra
• Vitamin D, which prevents rickets
• Vitamin C, which prevents scurvy
Drs. Eijkman and Hopkins shared the 1929 Nobel Prize for the discovery that vitamins are essential to maintain health.
When the anti-scurvy substance was given the name vitamin C, no one knew what it was. They knew that it was found in fruit, because pioneers such as James Lind had shown in the eighteenth century that citrus fruit could cure scurvy in sailors. However, there must be a specific chemical in fruit and vegetables preventing and healing scurvy for the vitamin C hypothesis to be correct. By 1928, Albert Szent-Györgyi, M.D., Ph.D., a Hungarian biochemist working in Cambridge, had isolated a strong antioxidant, a white powder found in fruit and vegetables. He realized that he had found the elusive vitamin C, for which he was awarded the 1937 Nobel Prize in medicine. Dr. Szent-Györgyi consistently suggested that people might need gram-level intakes of vitamin C for good health, but his views were in the minority.