NB: The author of this article is not a medical doctor and none of the information contained herein should be taken as medical advice. Copyright 2005, all rights reserved by the author. No reproduction of this article, in whole or in part, permitted without permission.
At the end of the 15th century, as Europeans developed the technology that allowed them to sail far away from shore and begin to explore the globe, a mysterious and deadly disease began to plague the sailors on these long distance voyages. Men were afflicted with blackened, ulcerated skin, fatigue, soft rotting gums and tooth loss, and in the late stages, uncontrolled bleeding including excruciating hemorrhage from the blood vessels serving the bone marrow. The disease was fatal for many of the men who accompanied explorers like Magellan, Vasco de Gama and others and could result in a loss of up to 80% of a ship’s company on a long voyage. Called the “scourge of the sea” by some and scurvy by others, its cause and, more importantly, its cure, were a complete mystery.
While the causative agent was unknown, the pattern of a scurvy outbreak was familiar to the sailors and medical professionals of the day. The disease would appear only after a ship had been at sea for several weeks and it would only continue until landfall was made again. Men afflicted with scurvy, and on death’s doorstep, would improve spontaneously once the ship had made port. Was this a disease caused by something in the open sea? Was it caused by the close quarters on the ship? Eventually, a connection with diet was made by a Scottish naval surgeon named George Lind in the middle of the 18th century. Lind observed that citrus juice could both cure and prevent the onset of scurvy. Based on his findings, the British navy began to provide each sailor with a daily ration of lime juice. Scurvy disappeared from the British navy who were thereafter known by many as Limeys.
Although the British had demonstrated that daily consumption of citrus could prevent scurvy, even in the early parts of the 20th century the disease was still an issue for people with highly restrictive diets including Robert Scott’s doomed expedition to the South Pole in 1912. It wasn’t until 1928, almost one hundred and seventy-five years after Lind published his findings, that the actual active compound was discovered. It was named ascorbic (anti-scurvy) acid by the team that discovered it. Ascorbic acid was later called vitamin C when, in 1933, it became the first vitamin to be synthesized and produced artificially.
How does vitamin C prevent and cure scurvy? It turns out that vitamin C is essential for collagen synthesis by hydroxlating the amino acids proline and lysine into the procollagen, the substrate for all types of collagen formation. Without this action, the body cannot repair collagen as it breaks down. Given the widespread occurrence of the various forms of collagen in everything from skin down to internal organs, an interruption in collagen synthesis will result in the horrific, and eventually fatal, symptoms of scurvy.
Fortunately, only a very small daily dose of vitamin C is required to keep collagen synthesis working, at least at the level needed to ward off clinical scurvy. A daily dose of 50-60mg is all that is required. Modern western diets usually achieve this with little difficulty through fruit drinks, fortified cereals or uncooked fruits and vegetables. Most multivitamin formulas contain at least this much ascorbic acid, and standalone vitamin C tablets are inexpensive and widely available in a variety of dosages.
In addition to its function in the collagen synthesis reaction, vitamin C also functions in the body as an antioxidant. Two of the byproducts of aerobic cellular metabolism are what are known as reactive oxygen species and free radicals. Because of their high reactivity potential, these metabolic byproducts can be damaging to tissues and human DNA.1 While the human body is capable of producing its own antioxidant chemicals, it also depends for on exogenous antioxidants like ascorbic acid, tocopherol (vitamin E), and retinol (vitamin A). The latter two vitamins are fat soluble while vitamin C is water soluble, meaning that they exert their respective antioxidant effects in different areas of the body depending on the lipid environment.
One of the oldest, and still leading, theories on human aging holds that it is caused by the cumulative damage done to our cells and DNA by free radicals.2 If this in fact true, it is also then possible that the provision of adequate amounts of free radical quenching compounds like vitamin C may mitigate this damage and prevent, or at least slow down, the aging process.
The US Recommended Daily Allowance (USRDA) for vitamin C is less than 100mg/day for all people. This is the dose required to prevent clinical scurvy. However, we now understand that vitamin C has other functions beyond supporting collagen synthesis. The question then becomes: what is the optimal dose of vitamin c and can doses above mere deficiency protection provide additional benefits? While this question is difficult to answer directly, there is certainly indirect evidence that the optimum dose for ascorbic acid in humans is a good deal higher than the current RDA.
The first evidence we have is a quirk of evolutionary biology. The vast majority of mammals can and do produce their own ascorbic acid from glucose. Humans have only three of the four enzymes required for the conversion reaction and cannot produce ascorbic acid internally. Aside from humans, among mammals, guinea pigs, fruit bats and some species of ape also cannot produce their vitamin C and must obtain it from diet alone. For the non-human members of this list, their vegetarian/high fruit diets provide copious amounts of ascorbic acid, likely much more than the equivalent of 1mg/kg needed to prevent clinical scurvy.3 If we examine the rate at which most mammals produce ascorbic acid and extrapolate to human size and metabolic rate, we find that an equivalent exogenous dose of ascorbic acid for a 70kg human would be something between four and six grams/day.4,5
Some more direct evidence for an optimal daily ascorbic acid dose in the multigram range comes from clinical experience with these doses in humans. Scurvy is essentially unknown in the United States today because almost all Americans consume at least 100mg frequently enough in their daily diet. It is somewhat telling, however, when people consuming this “typical” (and supposedly sufficient) dose are compared to those consuming much more. The clinical data suggests strongly that high dose (>1g/day) vitamin C appears to produce a wide variety of beneficial effects in humans.
Improved Vascular Tone
Vitamin C appears to improve the response of blood vessels to the vasorelaxant nitric oxide by protecting it from the effect of oxygen-derived free radicals. The impact of vitamin c supplementation on blood pressure has been mixed, but this is probably due mainly to the small doses (<500mg/day) used in many studies. In animal and some human studies, large dose ascorbic acid supplementation improves hypertension. 6,7,8
Plasma ascorbic acid levels are inversely related to the development of degenerative joint pain and osteoarthritis even when all other factors are controlled for. Individuals with the highest plasma AA levels are the least likely to suffer from joint degeneration probably due to the salutary effect of vitamin C on the formation and repair of collagen rich connective tissue. Antioxidants like vitamin C may also potentiate natural pain controlling chemicals called endorphins.9,10
Improved Reaction to Stress
High dose ascorbic acid has been demonstrated to mitigate some of the negative effects of both intense physical and psychological stress.11,12,13
Improved Resistance to Death and Disease
An epidemiological study published in 2000 showed that adults with high blood plasma ascorbate concentrations had a 57 percent reduced risk of dying from any cause and a 62 percent reduced risk of dying of all cancers compared to adults who had low plasma levels. Another large study involving over 6,000 participants showed a 27% reduction in the incidence of coronary heart disease and a 26% reduction in the incidence of stroke among those individuals with saturated plasma ascorbic acid levels compared to those individuals with the lowest plasma levels. Another European study involving close to 20,000 participants showed a 50% reduction in deaths from all causes among those with the highest plasma ascorbic acid levels independent of blood pressure, smoking habits and serum cholesterol levels. Finally, a ten-year US study published in 1992 involving over 10,000 participants showed that vitamin C supplementation was particularly beneficial for men. Those in the study who consumed more than 750mg/day saw a 35% reduction in mortality from all causes, a 22% reduction in cancer mortality and a 42% reduction in cardiovascular disease mortality.14,15,16,17
Improved Mood and Social Ability
A small, but well designed, study demonstrated that when compared with placebo, 3g/day of ascorbic acid improved mood and sexual frequency which the researchers attributed to lessened social inhibitons.18
We can see that vitamin C supplementation well in excess of the what is needed to prevent scurvy clearly has a wide range of positive effects. But what about perhaps the most common use of high-dose ascorbic acid supplementation, namely to prevent and treat the common cold? Although anecdotal evidence for its efficacy as a treatment for the common cold abounds, clinical studies do not support its use. A 2004 meta-analysis of 29 placebo-controlled studies showed little or no efficacy of vitamin c in treating the common cold.19 However, a more recent European study did find that “…vitamin C supplementation [of 500mg/day] significantly reduces the frequency of the common cold but had no apparent effect on the duration or severity of the common cold.”20 So while it probably won’t help once symptoms appear, prophylactic use of vitamin C may make sense.
Is taking hundreds or thousands of milligrams of ascorbic acid safe? Being water soluble, vitamin C does not accumulate in human tissues like some fat-soluble vitamins can. A number of studies have demonstrated that ascorbic acid intake by humans of up to 20g/day is safe and has no adverse health consequences aside from possible gastrointestinal upset which can largely be avoided by using a time-release supplement. A contention made in the journal Nature in 1995 that daily intake of more than 500mg of ascorbic acid could cause DNA damage has since been convincingly refuted and the long held theory that high doses of vitamin C will lead to kidney stone formation has yet to be established through clinical studies.
In short, ascorbic acid appears to be a safe and inexpensive way to help optimize the overall performance of the human body and reduce the incidence of disease.
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