Vitamin C for Immune Function

There have been remarkably competent and influential advocates of the positive effects of consuming high doses of vitamin C. Of these, Linus Pauling stands out, not only because he won the Nobel Prize but also because he was so adamant that vitamin C can treat many health problems. In the grip of the COVID-19 pandemic, interest in vitamin C has surged again due to this micronutrient’s roles in immune system regulation, and nowadays vitamin C is one of the most used supplements in the world. In the next couple of blogs, we’ll consider whether it’s worth supplementing vitamin C. We’ll explore the more consequential and interesting aspects of vitamin C, starting with the importance of vitamin C for immune function. Grab yourself a satsuma and let’s get to it.

 

Key takeaways

• Vitamin C deficiency results in scurvy, a disease characterised by fatigue, increased susceptibility to infections, impaired wound healing, depression and more.
• Vitamin C is key to many aspects of immune function, in part through its roles as an antioxidant.
• Vitamin C is also important to the integrity of barriers in the immune system (e.g., skin), helps some immune cells both move to sites of infection and kill pathogens, is involved in halting immune activity when it’s no longer beneficial, and can ultimately help generate antibodies that oppose foreign bodies.
• Regularly supplementing at least 200 mg vitamin C per day doesn’t generally reduce risk of getting a cold. However, taking 250 mg to 1 g per day about halves risk if you’re taxing yourself physically (e.g., doing strenuous endurance training).
• Regularly supplementing at least 200 mg vitamin C per day reduces how long colds last by about 8 % in adults and 14 % in children.
• If you don’t usually supplement vitamin C, it’s possible that taking very high vitamin C doses (e.g., 8 g per day) at the onset of cold symptoms and continuing for at least 5 days reduces the length and severity of colds.
• Giving critically ill COVID-19 patients vitamin C doesn’t seem to affect their risk of dying, but it might reduce risk of blood clots.
• It’s plausible that giving certain cancer patients mega doses of intravenous vitamin C helps halt cancer progressing by raising blood vitamin C levels well above what’s possible by oral intake.

  

Vitamin C deficiency and insufficiency

Vitamin C (ascorbic acid) is an essential micronutrient, meaning you won’t be able to survive long without it. The reason is that unlike plants and many animals, we humans lack an enzyme (gulonolactone oxidase) needed in the chain of steps that converts glucose or galactose into vitamin C. As a result, insufficient vitamin C intake can lead to deficiency (scurvy) over time, a disease characterised by symptoms including fatigue, increased susceptibility to infections, bleeding gums, impaired wound healing, increased bruising, skin problems, depression and more. Left untreated, scurvy is ultimately fatal. The role of vitamin C in treating scurvy was first documented in the mid-18^th century by Sir James Lind, a British Navy surgeon who cured this disease by giving men on board the HMS Salisbury citrus fruits. But it wasn’t until 1932 that scientists directly attributed this to vitamin C.

While scurvy is now relatively rare in “developed” countries, low levels of plasma vitamin C (“hypovitaminosis C”) are quite common, and vitamin C deficiency (defined as less than 11 µmol vitamin C per L blood plasma) is the fourth most prevalent nutrient deficiency in the US. I find this somewhat surprising, for many readily available and inexpensive foods contain lots of vitamin C – just a half cup of red pepper and an orange each day should more than meet government recommendations for even the neediest adults.

 

Vitamin C is an antioxidant

As seen in scurvy, insufficient vitamin C intake leads to poor immune function and high susceptibility to infections. Furthermore, infections lead to inflammation and increased metabolic rate, which tax your body’s stores of vitamin C at higher rates. The reason is that vitamin C is a water-soluble, non-enzymatic “antioxidant”. You needn’t dwell on the details, but this means vitamin C can donate an electron to highly reactive molecules named reactive oxygen species (e.g., singlet oxygen, superoxide, peroxides). During the process of donating an electron, vitamin C is transformed into an ascorbyl radical and then dehydroascorbate, which can finally be recycled back to vitamin C. Importantly, vitamin C can also help recycle other antioxidants (e.g., α-tocopherol, glutathione) and spare their oxidation. 

Optimal levels of reactive oxygen species are important to signaling in cells and help you improve your ability to tolerate the stress of things like exercise and heat. However, as they are short on electrons, reactive oxygen species seek electrons from structures in your body (e.g., DNA) and are therefore prone to damaging your cells. Reactive oxygen species therefore become harmful when they exceed your body’s capacity to counter them, so vitamin C’s antioxidant actions help defend your cells against this “oxidative stress” when under duress.

 

Vitamin C and the immune system

Vitamin C is not just an antioxidant. It supports both the branch of your immune system you’re born with (the “innate” branch) and the branch you develop as you interact with the world (the “adaptive” branch). The innate branch is made up of physical barriers (the skin, the gut lining, respiratory tract, etc), mucus layers, the cells that sweep the mucus (e.g., in the gut) and various types of cells and products released by these cells. Regarding physical barriers, vitamin C is a cofactor for enzymes that stabilise the structure of collagen, the most abundant protein in your body’s connective tissue. This effect on collagen in part explains how vitamin C supports wound healing. Beyond this structural role, vitamin C has antioxidant actions at immune system barriers. For example, vitamin C is actively transported into your skin cells, where it helps scavenges reactive oxygen species (e.g., due to air pollution).

Moving on to innate immune cells, the main cells are phagocytes. There are many of these, but neutrophils are the most abundant and are among your immune system’s first responders to injury or infection. Vitamin C improves how well neutrophils move in response to chemical signals and helps these cells kill foreign invaders. Vitamin C also helps neutrophils eventually exit sites of infection or undergo programmed cell death when they’ve done their jobs, which is important because neutrophils can otherwise die in a way that can damage nearby structures. 

And then there’s your adaptive immune system. If whatever your body is fighting isn’t cleared by the innate branch, the adaptive one kicks in. The latter detects components specific to individual pathogens, eventually producing antibodies against them. These antibodies are the basis of long-term memory in your immune system, and you’ve probably heard and read about them when finding out about COVID-19. Vitamin C’s roles in the adaptive immune system aren’t very well established, but vitamin C appears to help B and T cells proliferate and differentiate, supporting the manufacture of large numbers of antibody-producing cells.

During activity in either branch of the immune system, inflammatory processes help coordinate immune cells and amplify their responses when needed. While inflammation can be lifesaving, it’s a double-edged sword, for dysregulated inflammation can lead to tissue damage that underlies much chronic disease. Certain cytokines are particularly important to intensifying inflammation and are released by immune cells (and other cells) to call on additional immune cells for help. As adequate vitamin C helps normalise cytokine production and thereby match inflammation to needs, it prevents excessive inflammatory responses. Histamine is another chemical involved in inflammation, hence the use of antihistamines for allergies, and vitamin C can also dampen histamine responses to allergens.

  

Vitamin C for the common cold

Since it has so many roles in immune function, you’d probably expect vitamin C intake to influence the risk or severity of colds. Perhaps the best analysis of this to date found that when people from the general population supplement with at least 200 mg vitamin C each day, their risk of catching a cold doesn’t really change. However, when the scientists looked specifically at people doing demanding activities (marathon running, skiing, and military exercises), they found that supplementation with 250 mg to 1 g per day about halved risk of getting a cold. They also reported that vitamin C supplementation reduced how long colds lasted by 8 % in adults and 14 % in children, but only if supplementation was routine as opposed to beginning only after onset of a cold. Nevertheless, there is some evidence that taking mega doses of vitamin C (e.g., 8 g per day) starting on the day of onset of symptoms of the common cold and then continuing for at least 5 days can reduce the length and severity of colds.

  

Vitamin C for COVID-19

More recently, many of us have been interested in whether vitamin C supplementation can counter COVID-19. As has been true of many supplements and drugs, people have written speculative review articles hypothesising that additional vitamin C intake is a good idea during the pandemic. However, the actual studies aren’t very convincing. While COVID-19 patients have only about a fifth of the plasma vitamin C levels of healthy people, when researchers pooled findings from 6 studies that added vitamin C to treatment of COVID-19 patients, they found no effects on time spent in hospital, need for mechanical ventilation, or risk of dying. Interestingly, however, more recent work did show some positive effects in critically ill patients: adding 1 g per day of vitamin C to patients’ treatment did not affect mortality but did reduce the odds that patients would develop blood clots. So it might be that vitamin C is advantageous, just not necessarily in ways that some people expected.

I’ll add that there are ongoing clinical trials to determine whether intravenous vitamin C (as opposed to oral supplements) improves COVID-19 outcomes. My expectations are low, but we do know that the effects of oral vitamin C intake can differ from those of intravenous vitamin C – more on this below.

  

Vitamin C and cancer

While cancer is not an infection, immune system dysfunction can contribute to the development and progression of cancer. In part through its roles in the immune system, vitamin C might have some anti-cancer properties. For example, vitamin C’s antioxidant actions can oppose cancer-propagating oxidative damage. Vitamin C might reduce formation of some substances (e.g., nitrosamines) that promote cancer too. And some people believe vitamin C can halt cancer by hindering the ability of cancerous cells to use sugar for energy, for mega doses actually increase oxidative stress in malignant cells, inhibiting an enzyme (glyceraldehyde-3-phosphate dehydrogenase) that helps generate energy from glucose. 

This is all interesting, but the important question is whether vitamin C influences cancer risk and progression in humans. In general, people who report higher vitamin C intakes have lower risk of various cancers (e.g., breast, gastrointestinal and respiratory cancers). Predictably, cancer patients also tend to have lower blood levels of vitamin C. However, supplementing vitamin C (often alongside other micronutrients) doesn’t seem to affect risk of developing cancer.

Regarding the treatment of cancer, it isn’t yet clear whether vitamin C is helpful. Much of the early research produced contradictory findings, which probably related to how vitamin C was given to patients. Specifically, when you consume vitamin C orally, you absorb about 70 to 90 % of it at modest doses. But as the dose increases, absorption decreases such that above 1 g absorption is less than 50 % as the rest is excreted via urine. As a result, mega doses (3 g every 4 h) only raise blood vitamin C to about 3 times the level reached via a typical diet. In contrast, intravenous vitamin C affects blood levels in a much more linear way, and delivering vitamin C directly into a person’s veins can produce blood levels more than 100 times higher than taking mega doses by mouth. The significance of this is that the resulting blood levels of vitamin C appear to increase oxidative stress in a way that is selectively toxic to cancer cells, which could explain case reports of cancer patients living unusually long lives when given vitamin C in this way.

Please note that I’m not recommending this approach, and we don’t know much about how it might interact with other treatments including chemotherapy and radiation therapy. It’s surely a subject worth exploring though.

  

Until next time 

In the next blog we’ll look at whether vitamin C can help improve everything from diabetes to depression, and we’ll also review why inappropriate vitamin C supplementation can occasionally be a bad idea. I’ll end by sharing some thoughts on smart ways to supplement with vitamin C.

Stay tuned!