The Role Of Vitamin C In Immunity

Most of us know that vitamin C helps to fight colds, flus and other infections. You don’t have to look further than your cold medicine or cough drops to see that they contain some vitamin C. But have you ever wondered why vitamin C is so important?

The breadth of impact vitamin C has on our immune system may surprise you. If you are interested in underlying mechanisms like I am, you’ll enjoy today’s article. If you enjoy the bigger picture view, I have you covered too.

Keep reading to learn more about:

• Vitamin C basics for cell function
• The various roles vitamin C plays in immune health
• How vitamin C is essential for methylation balance (spoiler, it has to do with de-methylation)
• New research about vitamin C’s role in maintaining genetic stability in regulatory T cells (Tregs)
• How to know if you are getting enough vitamin C and when to add in a supplement

Let’s jump in! 

What Is Vitamin C? - Vitamin C Functions

Vitamin C, also referred to as l-ascorbic acid or ascorbate, is an essential water-soluble vitamin. While most animals synthesize their own vitamin C, humans need to obtain it from food. Without enough vitamin C, you may see negative impacts to the skin, poor immune function, and, in extreme cases, scurvy.

Vitamin C plays many important roles in the body, as a cofactor in metabolic processes, an antioxidant and a player in gene expression. Some of the main functions of vitamin C include:

• Cofactor in collagen biosynthesis, required for the structure and integrity of the skin, bones and connective tissues
• Cofactor in carnitine synthesis, required for energy production
• Cofactor in the production of catecholamine hormones: dopamine, epinephrine and norepinephrine
• Powerful antioxidant that protects cells and DNA from free radical damage and reduces oxidative stress. Important for cardiovascular health
• Helps to regenerate vitamin E, another important antioxidant
• Increases the bioavailability of dietary iron
• Regulates gene expression through de-methylation. More on this below. (Source 1)

For more information about the role of vitamin C in the body as well as the benefits, please read the article Science of the role of vitamin C in the : Benefits Beyond the Common Cold. 

Vitamin C and Immunity

While the benefits of vitamin C are far reaching, immune benefits get a lot of attention and for good reason! Vitamin C is essential for immune health and favorably impacts the immune system in several ways.

Vitamin C is important for both innate and adaptive immunity. The innate immune system is the body’s first line of defense against pathogens and provides general or non-specific immune function. Think: natural killer cells (NK cells), a specialized lymphocyte T cell, that can detect and destroy invaders directly.

Adaptive immunity is specialized and specific; it identifies a specific pathogen and then accurately destroys it. Think: B-cells that produce highly specific antibodies to a viruses and label them to be destroyed by cytotoxic T-cells. (Source 2) 

Because of these roles, vitamin C is considered and antiviral nutrient.

Here are some specific roles that vitamin C plays in immune function:

• Vitamin C creates a barrier. By promoting collagen production, vitamin C is important for maintaining the skin barrier that protects against pathogens. It is also important for the epithelial barrier of the lungs and gut, as examples, and may help to heal leaky gut. (Source 3, 4)

• Vitamin C accumulates in phagocytes, such as neutrophils, affecting neutrophil function. These are cells that ingest harmful particles, pathogens or dead cells. Vitamin C enhances chemotaxis (movement of cells), phagocytosis (engulfing of cells), generation of reactive oxygen species (used to attack) and the general killing of microbes. (Source 4)

• Vitamin C supports apoptosis (cell death) and the clearing of these cells from the site of infection. (Source 4)

• Antioxidant actions of vitamin C protects cells (including immune cells) and tissue from oxidative damage caused by the pathogen itself or the immune response to the pathogen. (Source 4)

• Vitamin C enhances the production and differentiation of immune cells, including both B cells and T cells, as well as helps these cells proliferate (multiply). Immune cells include leukocytes, macrophages and more. This effect is likely due to the gene regulating effects of vitamin C, which I will discuss shortly. (Source 4) 

Of note, B cells are immune cells that mature in the bone marrow and produce antibodies, while T cells are immune cells that mature in the thymus and help to remove pathogens from the body.

Overall, vitamin C is involved in defending the body from foreign invaders by both stimulating white blood cells and protecting them, and you, from damage. In addition, by balancing cytokine levels, vitamin C may also play a role in inflammation.

When levels of vitamin C are low, immunity is impaired and susceptibility to infectious diseases increases. Vitamin C is important for the individual and is also an incredibly important nutrient from a public health perspective.

Vitamin C and De-Methylation

As mentioned above, one of the ways that vitamin C is important for immunity is because of its effect on gene expression, or epigenetic regulation. 

To understand this, let’s quickly review methylation. For a more in-depth explanation, read my article The Methylation Cycle. 

Methylation involves the addition of a methyl group (a molecule with one carbon and three hydrogen atoms, i.e., -CH3) onto another molecule. This process, which requires folate and vitamin B12 among other cofactors, is foundational for millions of chemical reactions happening in every cell of the body. 

As an example, an enzyme called Cathecolamine-O-Methyl-Transferase (COMT) use these methyl groups to deactivate stimulating neurotransmitters like dopamine, norepinephrine and epinephrine, so that we are not on high alert constantly. 

Methylation is also required for detoxification, glutathione production, hormone production and metabolism, neurotransmitter synthesis as well as genetic expression we are discussing here. Methylation needs to be balanced, especially when it comes to DNA methylation: too little methylation impairs these systems and too much methylation is also an issue and may drive cancer. 

Just as there is methylation, there is also de-methylation, or the removal of a methyl group from another molecule or DNA. While methylation usually turns gene expression “on” and  is dependent upon B vitamins, de-methylation typically turns gene expression “off” and requires vitamin C. (Source 5)

Vitamin C, Tregs and TET Proteins

Regulatory T cells, or Tregs for short, are important immune T cells that help to control (decrease) inflammation and can increase immune tolerance preventing autoimmunity.  

Tregs contain Ten-Eleven Methylcytosine Dioxygenase Translocation de-methylation enzymes, or TET for short, which are important enzymes for maintaining the genetic stability and function of the Treg cells. (Source 5) 

And, TET proteins need vitamin C! 

Recent research from the La Jolla Institute for Immunology and Emory University School of Medicine shows that vitamin C and TET proteins work together to support maturation and proper function of Tregs that are grown in the lab. Previous attempts at in vitro (in culture) Treg production failed to produce stable cells, but vitamin C may change that, potentially leading to immune treatments for autoimmune disease and organ transplant. 

This study analyzed the gene expression (or epigenetics) in the iTregs (in vitro Tregs) and showed that vitamin C enhances the activity of the TET protein enzymes through de-methylation, making these cells more similar to the mature, properly functioning Tregs in the body which regulate autoimmunity. 

When methyl groups are removed from the DNA in the iTreg cells, the methyl groups become available to the TET enzymes, helping to maintain a favorable genetic expression. TET enzymes in the presence of abundant vitamin C also made Tregs more responsive to a peptide called Interleukin-2 (IL-2) which is responsible for proliferation and proper functioning of Tregs. (Source 6)

A balance between methylation and de-methylation is required for immune cell health and epigenetic regulation. Vitamin C is a key factor in de-methylation, playing an important role in the proper functioning of Treg cells which in turn regulate autoimmunity. 

Do You Need More Vitamin C?

Despite the availability of vitamin C in the diet, vitamin C deficiency is the fourth common nutrient deficiency in the United States. (Source 7) You may be at risk for low vitamin C levels if you don’t eat many fruits or vegetables, abuse alcohol, smoke cigarettes or have a disease that increases your requirements for this nutrient. (Source 4)

The recommended dietary allowance RDA for vitamin C is 90mg per day for adult males and 75mg per day for adult females. Scurvy occurs with intakes under 10mg per day. (Source 1)

However, amounts around 100-200mg of vitamin C per day may be required to maintain adequate levels in the blood for prevention of infection. Much larger dosages may be required to treat an infection because of the metabolic demand for vitamin C and increased inflammation under these circumstances. (Source 4)

Adequate levels can often be maintained by regular consumption of vitamin C rich foods and moderate supplementation based on individual needs. 

Good food sources of vitamin C to include in the diet are:

• Rosehips
• Bell peppers
• Broccoli
• Strawberries
• Oranges
• Grapefruit
• Brussels sprouts
• Tomatoes 
• Kiwifruit

Micronutrient testing may be supportive to determine if your diet is meeting your individual needs or if you would benefit from higher levels of vitamin C obtained through supplementation. 

Vitamin C Supplements – Dosages, Downsides and Liposomal Solution

Vitamin C supplements are available as powders, liquids and as intravenous vitamin C.

Core Med Science’s multivitamin, Liposomal Active B-Complex + Minerals, contains 60mg of vitamin C and should have the daily needs covered for a healthy person who also consumes produce regularly. However, in many cases daily requirements may be higher and taking additional vitamin C as a dietary supplement may be supportive. 

At the very least, I recommend keeping vitamin C on hand to use at the onset of colds, flus, infections or to help with wound healing.

The Institute for Functional Medicine recommends a vitamin C intake of 1-3 grams (1000 to 3000mg) per day as part of a treatment for COVID-19, which is similar to recommendations for other acute immune support. (Source 8)

Two main issues arise with vitamin C supplementation. First, vitamin C supplements are poorly absorbed. And second, high dose vitamin C may produce the side effect of digestive upset and loose stools, making it challenging to achieve a therapeutic dose. 

Liposomal delivery solves these problems by increasing absorption and bioavailability while being well tolerated. 

Core Med Science’s Liposomal Vitamin C packages non-GMO vitamin C (Quali-C brand sourced from Scotland) inside liposomal particles made from non-GMO phosphatidylcholine derived from sunflower. Because these liposomes resemble our own cells, more vitamin C is absorbed and higher dosages are comfortably achieved. You might even have better results with lower dosages when utilizing our liposomal product, which is available as both a liquid and capsule.  

Vitamin C is a nutrient we may not give a lot of thought to daily but is incredibly important for overall health and the proper functioning of the immune system. This deep understanding may lead to new treatments for immune conditions including autoimmune disease, and also helps us to be consistent with vitamin C consumption through food and supplements to optimize personal wellness.  

References

1. Linus Pauling Institute: Micronutrient Information Center. (2018). Vitamin C. Accessed 8/18/21. Available from: https://lpi.oregonstate.edu/mic/vitamins/vitamin-C

2. Institute for Quality and Efficiency in Health Care (IQWiG) (2020). The innate and adaptive immune systems. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279396/ 

3. Guo, Y., Mah, E., & Bruno, R. S. (2014). Quercetin bioavailability is associated with inadequate plasma vitamin C status and greater plasma endotoxin in adults. Nutrition (Burbank, Los Angeles County, Calif.), 30(11-12), 1279–1286. Abstract: https://pubmed.ncbi.nlm.nih.gov/25280405/ 

4. Carr, A. C., & Maggini, S. (2017). Vitamin C and Immune Function. Nutrients, 9(11), 1211. Full text: https://www.mdpi.com/2072-6643/9/11/1211 

5. Camarena, V., & Wang, G. (2016). The epigenetic role of vitamin C in health and disease. Cellular and molecular life sciences: CMLS, 73(8), 1645–1658. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805483/ 

6. Yue, X., Samaniego-Castruita, D., González-Avalos, E., Li, X., Barwick, B. G., & Rao, A. (2021). Whole-genome analysis of TET dioxygenase function in regulatory T cells. EMBO reports, 22(8), e52716. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339674/ 

7. Schleicher, R. L., Carroll, M. D., Ford, E. S., & Lacher, D. A. (2009). Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES). The American journal of clinical nutrition, 90(5), 1252–1263. Abstract: https://pubmed.ncbi.nlm.nih.gov/19675106/ 

8. The Institute for Functional Medicine. (2020). COVID-19 Functional Medicine Resources – The Functional Medicine Approach to COVID-19: Virus Specific Neutraceutical and Botanical Agents. Accessed 8/18/21. Available at: https://www.ifm.org/news-insights/the-functional-medicine-approach-to-covid-19-virus-specific-nutraceutical-and-botanical-agents/