In 1970, double Nobel Prize laureate Dr. Linus Pauling published Vitamin C and the Common Cold, in which he posited that consuming large amounts of vitamin C could reduce the duration and severity of the common cold. The book effectively put vitamin C on the nutritional map, establishing it as a cure-all in the collective minds of the lay public. Nearly a decade later, Pauling published clinical data suggesting that high dose intravenous administration of vitamin C showed promise as a supportive treatment for cancer as well as a strategy to mitigate the side effects of chemotherapy. Pauling's work was heavily criticized in the scientific community, however, due to a lack of proper controls and standardization. Since then, countless studies have tested Pauling's theories about vitamin C, colds, and cancer (and many others), and a substantial body of evidence has emerged, identifying critical roles for vitamin C in immune function, cardiovascular and respiratory health, cognitive development and preservation, and many other aspects of human health.
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Bioavailability of vitamin C
The absorption, distribution, metabolism, and excretion of vitamin C are complex and differ considerably from other low molecular weight compounds. Consequently, the bioavailability of vitamin C is both frequency- and dose-dependent. But the form of vitamin C impacts bioavailability, too. For example, oral vitamin C is absorbed in the small intestine via specialized transporters that are subject to saturation, but intravenous vitamin C bypasses the gut, achieving blood and tissue concentrations that are markedly higher than those achieved with the oral form. In fact, in healthy adults, intravenous administration of vitamin C can reach blood concentrations that are 30 to 70 times higher than equivalent oral doses.
Vitamin C as antioxidant
Much of vitamin C's effectiveness arises from its capacity to serve as an antioxidant – readily donating electrons to oxidized molecules, thereby quenching reactive oxygen species and preventing oxidative stress. This is perhaps best demonstrated in neutrophils, a type of immune cell that actively participates in eliminating pathogens from the body. Neutrophils generate large quantities of reactive oxygen species, putting them at risk for oxidative stress-induced DNA damage. Vitamin C is highly concentrated in neutrophils, however, with concentrations averaging roughly 50 times higher than plasma concentrations. In a strange paradox, the high levels of vitamin C present in neutrophils protect them from reactive oxygen species-induced DNA damage while simultaneously promoting the molecules' production.
Vitamin C as anti-infectious agent
After more than 50 years of research, the evidence supporting vitamin C's effectiveness against the common cold is still variable, likely due to widespread inconsistencies in study methodologies that span an extensive range of protocols. Despite these inadequacies, meta-analyses broadly demonstrate a protective effect, particularly with higher doses. However, even under the most rigorous testing, vitamin C likely shortens or lessens the duration of the common cold by hours, not days. Some populations, such as children and endurance athletes – who tend to have more colds than the average person – seem to benefit more from vitamin C's effects, especially when taken prophylactically.
Other data suggest that vitamin C reduces the risk of a litany of viral infections, from chickenpox to shingles to HIV. Perhaps more compelling are the data supporting vitamin C's use in the treatment of sepsis, a life-threatening condition that can arise when the body responds to a bacterial or viral infection. Sepsis ravages the body, provoking severe injury to multiple tissues and organs, often resulting in death. Recent evidence indicates that SARS-CoV-2, the novel coronavirus that causes COVID-19, induces sepsis. Interestingly, people who have sepsis often exhibit low vitamin C levels, which might be predictive of increased risk for organ failure. Vitamin C might be an effective treatment for sepsis because it modulates the proinflammatory state associated with sepsis and preserves organ function.
The beneficial properties of vitamin C extend beyond its ability to support immune function support and prevention of colds, conferring a wide range of salubrious effects on multiple organ systems, including respiratory, cardiovascular, neurological, and reproductive systems.
Vitamin C as lung defense
The innate immune system of the lungs is an integral component of the body's defense system, protecting the body against exposure to inhaled oxidants and pathogens. Vitamin C participates in this protective role by boosting immune cell function and reducing oxidative stress. Vitamin C's lung defense capacity is evidenced by robust data suggesting that vitamin C intake protects against chronic obstructive pulmonary disease, pulmonary fibrosis, and other respiratory illnesses, including lung cancer.
But this characteristic takes on special relevance in light of recent concerns about complications associated with COVID-19, such as pneumonia and acute lung injury, which often necessitate mechanical ventilation support. Epidemiological and observational data indicate that higher vitamin C intake is associated with a lower risk of developing pneumonia, and the vitamin has also proven to be effective at decreasing the duration for which patients are kept on mechanical ventilation, especially among patients who require more than 24 hours of breathing support.
Vitamin C as cardioprotective agent
Large, population-based studies have found that vitamin C confers protection against hypertension – a risk factor for cardiovascular disease and stroke, two of the leading causes of death among people living in the United States. Analysis of data from several randomized placebo-controlled clinical trials involving more than 1,400 participants indicates that oral vitamin C elicits significant reductions in blood pressure among people with hypertension. Furthermore, recent research suggests that intravenous vitamin C can reduce blood pressure in patients diagnosed with prehypertension, a risk factor for hypertension.
Vitamin C is found in high concentrations in the brain, especially in the hippocampus and frontal cortex regions – areas involved in memory consolidation, learning, and aspects of executive function. In fact, in a classic example of the body triaging resources based on needs, the brain retains vitamin C during times of deficiency at the expense of other tissues. This is critical to our survival: Evidence suggests that vitamin C plays roles in the brain throughout the lifespan from development through older age.
For example, studies in humans indicate that vitamin C concentrations are markedly higher in the fetal and newborn brain, and poor vitamin C status reduces hippocampal development. In older age, vitamin C's antioxidant capacity might be beneficial in decreasing the risk of neurodegenerative conditions like Alzheimer's disease, Parkinson's disease, Huntington’s disease, and multiple sclerosis by reducing oxidative damage – a key driver of neurodegenerative disease. Vitamin C is also important for the regulation of neurotransmitters, the formation of neural circuits, and many other key brain functions.
Vitamin C as chemoprotective agent
Vitamin C has been put to the test against many types of cancers, including glioblastoma, melanoma, and pancreatic, ovarian, colorectal, and non-small cell lung cancer. The findings from many of these studies suggest a trend in the overall survival rate for patients administered moderate doses of intravenous vitamin C in conjunction with standard therapies such as chemotherapy or radiation, even among patients with pancreatic cancer and ovarian cancer, two of the deadliest forms of cancer. These results have not been recapitulated with high oral doses of vitamin C, however.
Perhaps an equally important characteristic of vitamin C for people undergoing cancer treatment is its capacity to improve the patients' quality of life. Traditional therapies for cancer often ravage the body, eliciting both acute and chronic physical, emotional, cognitive, and sexual impairments. Terminal cancer patients who have received a combination of oral and intravenous vitamin C have noted marked improvements in their quality of life.
Vitamin C as performance enhancer – or hindrance
Vitamin C appears to enhance exercise performance by reducing the potential negative consequences of excess reactive oxygen species – highly reactive molecules produced during not only normal metabolic processes but also during exercise, as a consequence of exercise-induced immune activation. Excessive exercise-induced reactive oxygen species can promote muscle damage, fatigue, and immune dysfunction, but the extent varies according to the duration and extent of exercise. For example, high-intensity exercise such as long-distance running is linked to an increased incidence of upper respiratory infection.
Conversely, evidence suggests that reactive oxygen species might also mediate beneficial training adaptations as a part of a biologically useful signaling cascade. The downstream consequences of this cascade could blunt the beneficial training adaptations that reactive oxygen species might induce, such as increased mitochondrial number and function, improved insulin sensitivity and glucose utilization, and enhanced immune function, among others.
Vitamin C as potential kidney stone risk: a nuanced discussion
Although vitamin C is safe and well-tolerated in most healthy people, it has been implicated in an increased risk for developing kidney stones due to the formation of oxalate, an end product of vitamin C metabolism. The kidneys typically filter oxalate and excrete it in urine, but when high amounts of oxalate are present, it can form crystal structures with calcium and, in turn, promote the formation of kidney stones in high-risk people, such as those with existing kidney dysfunction. Yet large prospective cohort studies have found that high vitamin C intake increases the relative risk of kidney stones in healthy people. However, these findings were reached only after the creative manipulation of the data to predict theoretical risk, not actual risk. In reality, no association between vitamin C intake and kidney stones was identified.
Vitamin C as victim of less than rigorous study methodologies
The seemingly contradictory findings from much of the research on vitamin C arise from differences in study design, populations, dose, and delivery modalities, as well as a host of other factors. Resolving these inconsistencies presents a conundrum to the research community. Solutions might lie in simply ensuring that future studies utilize consistent, equivocal study designs, and in so doing, can elucidate the full potential of vitamin C in benefiting human health.
