Vitamin C, Nutrition and Disease

Y. Li is a graduate student and Dr. Schellhorn is a Professor, Department of Biology, McMaster University, Hamilton, Ontario, Canada.

Most of us know about the perils of too little vitamin C from our studies of history: the stories of the explorers, sailors and colonists who, deprived of fresh fruits and vegetables on long sea voyages, developed scurvy, which often caused serious illness and death. During the period of European colonial expansion, finding a cure for scurvy was not only a major medical problem but also a military and economic imperative for any nation with global ambitions.

It also proved to be difficult, despite the enormous attention devoted to it, because of medicine's poor understanding of the disease. Today we know that the answer turned out to be Vitamin C, a simple substance that not only cures and prevents scurvy but also has other potential therapeutic effects, which are still being discovered today.

Vitamin C is a generic term used to describe all ascorbate compounds, including ascorbic acid, dehydroascorbic acid and ascorbate salts. (The term "vitamin" comes from "vital amine," a term coined in the early 20th century. This is somewhat of a misnomer because these we know now that these compounds do not have any amino groups. However, the term "vitamin" has gained such popularity that it has stuck.)

'Nothing emphasizes the importance of vitamin C to human beings more than the effect of being without it for a relatively short time.'

Because of its effect against an array of diseases, vitamin C has been credited with almost magical properties. Although using it to treat diseases such as cancer and heart disease remains controversial, the importance of vitamin C in human health is universally recognized. As one authority rightly put it, "Nothing emphasizes the importance of vitamin C to human beings more than the effect of being without it for a relatively short time."

Animals Do It; We Can't

L-ascorbic acid, a naturally-occurring and biologically active form of vitamin C, exists as white crystals and is freely soluble in water. Most non-human animals can make their own vitamin C, but humans cannot. We must rely instead on eating foods that contain vitamin C in order to survive. This state of affairs — in effect a nutritional defect of our species — was caused by a genetic mutation estimated to have occurred around 40 million years ago.

The fact that this mutation spread throughout the human population raises the question of whether or not this "nutritional defect" is associated with certain evolutionary advantages. While the answer to this question is unknown, several hypotheses have been proposed. For example, some scientists speculate that the ultimate cause was a prehistoric viral infection that caused genetic damage which knocked out our ability to manufacture vitamin C. But because our ancestors lived in warm climates that were extremely rich in foods containing vitamin C, the nutritional consequences of this defect didn't really show up. As this theory has it, this inability to produce vitamin C internally likely caused an accumulation of free radicals within the body (as discussed below), which, in turn, resulted in an increase in the mutation rate of bodily cells, which, in turn, sped up the evolutionary transition to modern day Homo sapiens.

This idea of ascorbic acid influencing the rate of mutation and, consequently, evolution is supported by the fact that increased levels of free radicals are known to promote HIV replication, whereas ascorbic acid slows down the replication cycle.6 This could be one reason why natural selection favored the loss of our ability to synthesize vitamin C, especially when vitamin C is available from diet. By reducing human longevity, the loss of vitamin C producing-ability may also have selected against aging populations and made more food available for younger and more fertile individuals within early human populations, perhaps in a time of food shortages — in effect, thinning the human herd to the ultimate benefit of the survival of the species.

What Vitamin C Does for Your Body

The healing power of foods containing vitamin C had been understood long before the discovery of the vitamin itself. As early as 17th century, more than three hundred years before the chemistry of ascorbic acid was known, lemon juice was used by some to help prevent scurvy and treat the tooth loss, broken blood vessels and impaired wound healing associated with it. These symptoms are the result of a collagen deficiency brought on by a lack of vitamin C.

Vitamin C affects mood and energy levels. Depression and hypochondria are common symptoms of vitamin C deficiency. These are caused by norepinephrine deficiency, which results from the inadequate conversion of dopamine to norepinephrine in the absence of ascorbic acid. Vitamin C deprivation often also leads to a condition that impairs fatty acid metabolism and produces fatigue and lethargy.

Vitamin C is also essential for the absorption of iron by our bodies. Lack of vitamin C can lead to iron deficiency anemia, which is characterized by pallor, fatigue and weakness.

How We Process Vitamin C

When we take vitamin C, it is absorbed in the small intestine and enters the circulatory system from there.While circulating in the blood, vitamin C is filtered by the kidneys. The filtered vitamin C is then reabsorbed into the blood.

There are limits, however, to the amount of vitamin C that the body can process. Excess vitamin C, as a water-soluble vitamin, is simply excreted into the urine. For this reason, taking large quantities of vitamin C orally cannot raise and maintain ascorbic acid levels in the blood. The bottom line is that vitamin C cannot be stored for long periods in our bodies. We need to take in a consistent supply of vitamin C through our diet.

The current recommended daily allowance (RDA) for vitamin C, set by the Food and Nutrition Board of the U.S. National Academy of Sciences, is 75 mg per day for adult women and 90 mg per day for adult men. This value is derived from the estimated average requirement or vitamin C, which is the amount of vitamin C required by half of the healthy population at a certain life stage.

Another RDA, however, based on the adequate intake (AI) value, has also been proposed. The AI value is calculated from a group of healthy individuals and so is more useful for establishing the best levels of nutrient intake for individuals. Based on this value, it is recommended that 200 mg of vitamin C should be taken per day. This equals about 5 servings of fruits and vegetables. At this level, our bodily tissues will soon absorb the maximum amount of vitamin C that is possible. Although vitamin C can come from a variety of sources, including dietary supplements, the best way to get vitamin C is directly from the food we eat. Therefore, 5 servings of fruits and vegetables are recommended for all healthy individuals under normal conditions ).

People who smoke and those who are exposed to cigarette smoking need more vitamin C than those who don't smoke or are not exposed. Cigarette smoke contains free radicals which deplete vitamin C.

Vitamin C and Cigarettes

People who smoke and those who are exposed to cigarette smoking need more vitamin C than those who don't smoke or are not exposed. Cigarette smoke contains free radicals which deplete vitamin C. Smoking can reduce serum vitamin C levels by up to 40%. Nevertheless, taking moderate doses of vitamin C supplements can efficiently restore proper vitamin C levels in smokers.24

Vitamin C and Iron

Vitamin C facilitates our body's absorption of iron. While this is definitely a good thing, a small percentage of the population suffers from a condition called hereditary hemochromatosis, which can cause them too absorb too much iron, which in turn can damage cells and tissue. In most cases, these people should avoid taking vitamin C supplements. The frequency of hereditary hemochromatosis in Caucasian populations is 0.4-1%, and it can be identified with a simple test. Your doctor should run one of these tests before recommending that you or a loved one take extra vitamin C.

Kidney Stones

One of the byproducts left over after the body metabolizes ascorbic acid is a substance called oxalate, which can help cause a type of kidney stones. While studies on the question of whether or not taking vitamin C leads directly to kidney stone formation have been inconclusive, people who are prone to kidney stones should talk to their doctor before taking vitamin C.

The Best Sources of Vitamin C

Fresh fruits and vegetables are the best sources of vitamin C. Some of the more common dietary sources of vitamin C are listed in Table 1. It should be noted, however, that vitamin C content can depend on how food is stored and prepared. For example, boiling vegetables may result in 50% to 80% vitamin C loss. Lack of freshness can also significantly reduce vitamin C content.

Table 1.

Dietary Sources of Vitamin C.

Source (Size)	Vitamin C, mg
Fruit
Strawberries (1 Cup, sliced)	95
Kiwi fruit (1 medium)	75
Orange (1 medium)	70
Cantaloupe (1/4 medium)	60
Mango (1 Cup, sliced)	45
Watermelon (1 Cup)	15
Juice
Orange (1 Cup)	100
Grapefruit (1 Cup)	70
Fortified Juice
Grape (1 Cup)	240
Apple (1 Cup)	100
Cranberry cocktail (1 Cup)	90
Vegetables
Pepper, red or green Raw (1 Cup) Cooked (1 Cup)	130 100
Broccoli, cooked (1 Cup)	120
Brussels sprouts, cooked (1 Cup)	100
Cabbage Red, raw (1 Cup) White, raw (1 Cup)	40 20
Cauliflower (1 Cup)	50
Potato, baked (1 Medium)	25

Levine et al. 1999. Criteria and Recommendations for vitamin C intake JAMA. 281:1415-1423. (used with permission).

Vitamin C's Effects on Cancer

The potential anti-cancer effect of vitamin C is a controversial topic. Using vitamin C for cancer prevention and treatment was first proposed in 1949, and was supported by a number of physicians and scientists, (including Linus Pauling), who showed that the survival rate of terminal cancer patients could be improved by giving them high-dose, intravenous vitamin C. However, a later study at the Mayo Clinic, using randomized, placebo-controlled methodology, cast doubt on the effectiveness and reliability of megadose vitamin C therapy.

Some of the difference in these findings may be attributable, at least in part, to the difference in how the vitamin C was given. In the 1974 study, vitamin C was delivered by mouth and intravenously, whereas in the Mayo Clinic study it was administered by mouth only. As we have said, there is a limit to how much vitamin C can reach the bloodstream when it is taken orally. Much higher levels can be achieved, however, if the vitamin C is administered intravenously. Therefore, it is likely that higher effective vitamin C concentration was achieved in the earlier study than in the Mayo Clinic study.

Despite extensive research and public attention over the years, vitamin C has not yet been proven effective in treating cancer.

Recent research has, however, identified mechanisms that may explain whatever anti-cancer properties vitamin C may have. As a potent antioxidant, vitamin C protects cells from oxidative DNA damage, a known cause of cancer. In addition to its direct antioxidant effects, vitamin C makes cancerous cells more susceptible to apoptosis, or programmed cell death. Vitamin C also helps prevent uncontrolled cell proliferation, which contributes to cancer growth.

This research shows how vitamin C could function as an anti-cancer agent. In light of these new developments, an interventional study using high-dose intravenous vitamin C in the treatment of cancer in human subjects was approved by the FDA and entered phase I trial in 2007. This is the first officially-conducted interventional study examining the anti-cancer] effect of vitamin C and its findings, which are expected in 2009, should yield information that will help determine the value of this vitamin as a cancer fighter.

Vitamin C's Effects on Cardiovascular Disease

Since oxidative damage also contributes to cardiovascular disease, ascorbic acid may have a positive effect on heart disease. Epidemiological studies have confirmed that eating vitamin C-rich foods such as fresh fruits and vegetables is associated with a reduced risk of cardiovascular disease. However, because people who eat healthy diets tend to live generally healthy lifestyles (not smoking or drinking to excess, for example), it is unclear whether vitamin C is really the causal factor in the reduction of heart disease. Some studies have actually found the opposite.

Epidemiological studies have confirmed that eating vitamin C-rich foods such as fresh fruits and vegetables is associated with a reduced risk of cardiovascular disease.

As with cancer, in recent years scientists have changed their focus from trying to find a "cure" to identifying possible mechanisms by which ascorbic acid might interfere with heart disease-inducing processes.

Cardiovascular disease often begins with oxidative damage from naturally- occurring substances such as reactive oxygen (ROS) or reactive nitrogen species (RNS). Accumulation of these substances in the body has several detrimental effects on the cardiovascular system. First, they modify low density lipoprotein (LDL), leading to the formation of highly reactive oxidized LDL (oxLDL) cells, which are more likely to clog blood vessels, promote inflammation, and cause the death of cells lining the blood vessels. These events are the precursors of artery-clogging atherosclerotic lesions.

Vitamin C interferes with these processes in a number of ways. For example, ascorbic acid reduces the amount of ROS and RNS in the blood. It makes LDL more resistant to oxidation and thus slows the formation of oxLDL. Vitamin C also counteracts oxLDL-induced inflammation and cell death, preventing the formation of lesions within the blood vessels.

The anti-atherosclerotic properties of ascorbic acid are significantly increased when it is combined with vitamin E. The cooperative interactions between these two vitamins form the basis for co-antioxidant therapy in the treatment of heart disease, which is becoming increasingly accepted by the medical community.

Conclusions

While vitamin C is essential for the healthy functioning of the human body, its role in treating diseases such as cancer and heart disease has not yet been proven. Nevertheless, intensive research has shed light on the molecular mechanisms by which vitamin C interferes with disease-related processes. For example, the ability of vitamin C to selectively target and kill cancer cells, among other things, suggests that vitamin C may be a potential anti-cancer agent.

In addition, completely unexpected functions of vitamin C that may have important medical implications have recently been discovered. For example, ascorbic acid stimulated transformation of mouse embryonic stem cells into cardiac muscle cells, which may ultimately result in cardiac tissue regeneration for heart transplantation. While in the early stages, the applications of this new knowledge regarding vitamin C hold great promise.

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