You may have heard that vitamin A was good for your eyes and you're not wrong, however it does so much more than help us with night vision and remind us to eat our carrots. Did you know that vitamin A originally was called “the anti-infective vitamin"? I didn't either until I wrote this blog. The list of ways it benefits our immune system would literally require a 2-ton book. It turns out our immune system is pretty weak without vitamin A because of its importance in boosting the function of the immune system, especially in the skin and the mucosal cells that line our airways, digestive tract and urinary tract (1). We commonly overlook the barriers (skin and mucosal lining) as the most important part of our immune system. Keeping pathogens out is actually the most important part, as this is our first line of defense. We also don't want our white blood cells (WBCs) to have to initiate a response at all if it can be avoided.
Vitamin A is actually a generic term that refers to fat-soluble compounds found as preformed vitamin A (retinol) in animal products and as provitamin A carotenoids in fruit and vegetables (carrots). The three active forms of vitamin A in the body are retinol, retinal, and retinoic acid (2).
#1: Vitamin A Boosts Immune Cell Function
Vitamin A is produced (as retinoic acid) by our immune cells (APCs, macrophages and dendritic cells) that live in the mucosal linings of our airways, gut, our entire lymph system and have quick access to the skin should an invader try to break in. One of these cells called a dendritic cell (dendrite = branch), has many tiny arms like an octopus that allow it to engulf and literally eat foreign particles. Dendritic cells also display antigens (toxins, proteins, sugar coated molecules) that stimulate an immune response either by signaling WBCs to spring into action, by signaling for more help from other cells or by signaling the the production of antibodies. A simple way to think of an antibody is a "tag" that disarms viruses and bacteria and that WBCs look for to attack. Vitamin A allows dendritic cells to grow, move (or migrate) and properly display antigens so our immune system can remove it safely (3).
Vitamin A (retinoic acid) is also required for young CD4 T-lymphocytes cells to turn into regulatory T-lymphocytes (Tregs). The significance of this is that CD4 cells call all the other immune cells into action (sort of the battlefield general), and Tregs also balance out that immune response by suppressing it so it doesn't escalate to an autoimmune level and attack everything without regard for collateral damage. Vitamin A regulates the genetics of the cells that develop into Tregs, literally controling their growth and maturity, which is crucial to maintain the function of mucosal strength in the gut and airways. On the flip side, our body sometimes needs the ability to immediately spring into action and fire up inflammation to it's highest level. Vitamin A also plays a role in flipping the switch by turning young CD4 cells into T-lymphocyte--type 1 helper (Th1) cells (all-trans-RA/RARα signaling pathway), rather than Tregs, which drives inflammatory proteins (cytokines) to be produced so the infectious invader can be destroyed quickly. Vitamin A is required to prevent autoimmunity, as well as promote a precise attack when needed. It plays a crucial role in ramping up, or dampening the inflammatory response and keeping it from getting out of control and damaging our body's own tissue (3).
#2: Vitamin A Boosts Barrier Function
The first line of defense is the most important, especially when we consider that 95% of infections are initiated in the gut, airways, urinary tract, and even more than that when we include our skin, eyes and ears as well. When our body has a viral infection our demand for vitamin A increases substantially. Part of the reason for this increased need is that vitamin A is required for our body to make secretory IgA, the main antibody found in our bodily secretions (what a gross word) that are produced by our plasma cells. IgA disables viruses and bacteria making them harmless and literally attaches a target on the pathogen's back. The more secretory IgA we produce the quicker we kill viruses. Vitamin A is also essential to the production and secretion of mucous produced in our gut, airways and urinary tracts, and also essential to ensure the proteins between the cells in our skin, gut and urinary tract stay locked together tightly (4,5). Without vitamin A our barriers are weakened and their primary functions are left vulnerable which allows pathogens to enter deeper layers of defense and get closer to entering our bloodstream.
#3: Vitamin A Prevents a Virus from Spreading
Vitamin A has been studied extensively for its association with infectious diseases. Essentially what these associations reveal is that those who are deficient have a much higher risk of infection with a variety of viruses and pathogenic bacteria (6). How does vitamin A contribute to our body's innate defenses? One major mechanism is by it's influence on the gut microbiome.
An emerging mechanism shows the ability of vitamin A to use the gut microbiome (Lactobacillaceae, Allobaculum, Aggregatibacter, Bifidobacterium, Dialister, and Enhydrobacter) to promote the growth of good strains that kill the virus/pathogen. Another mechanism is vitamin A's ability to activate genes that allow our cells to produce weapons of defense. These weapons scramble the signals the virus needs to spread and reproduce and allows our immune cells to remember the virus so it can be killed when it's encountered in the future.
Vitamin A also activates the RIG-1gene, which produces type 1 interferon, (protein molecule that keeps neighboring cells from being infected) balances immune cell responses and activate immune system memory (via T- and B-Cells). Vitamin A compounds also closely regulate the growth and genetic expression of the cells that line our airways and these compounds have been known in part to regulate the mechanisms that control the activity of viruses, potentially allowing them to become more or less potent (7). Without vitamin A our body would allow viruses to hijack our cells, continually sneak in undetected and infect the cells that literally provide our body with important barriers from the outside world.
Vitamin A and Infectious Disease Prevention
Avoiding vitamin A deficiency is important but maintaining sufficient amounts during infections is equally important as well. Poor vitamin A status or deficiency makes people prone to infections and this super nutrient has quite a bit of evidence that shows that it lives up to it's "anti-infective vitamin" name. In fact vitamin A deficiency can be considered a nutritionally acquired immunodeficiency disease (11,12). To highlight this importance I wanted to point out the role vitamin A plays in reducing major infections with links to multiple studies on each:
-Antiviral Mechanisms: 1, 2, 3, 4, 5, 6
Recommendations:
Many of us have trouble turning carotenoid pre-vitamin A forms such as beta carotene in fruits and vegetables to the activated retinoid form called retinol. The efficiency of this conversion depends on people's genetics (8,9). The best dietary sources of vitamin A include liver and fish oil. However even with poor conversion it is still important to consume orange fruits and veggies such as sweet potatoes, carrots, squash, apricots, peaches and peppers.
Here's a list of the top 10 foods to consume for vitamin A:
The RDA is the estimated amount of vitamin A that the vast majority (about 97.5%) of people need to meet their daily requirements. The tolerable upper intake limit (UL), is the highest level of daily intake considered safe for 97.5% of healthy people (10).
The recommended daily allowance (RDA) for vitamin A: 3,000 IU (900 mcg) for adult men and 2,333 (700 mcg) for women. For children, it ranges from 1,000 IU (300 mcg) to 2,000 IU (600 mcg). Of course under a doctor's supervision higher doses may be recommended for individual clinical scenarios.
References
1. https://pubmed.ncbi.nlm.nih.gov/20774205-vitamin-a-as-an-anti-infective-agent/
2. Groff JL. Advanced Nutrition and Human Metabolism. 7th ed. St. Paul: West Publishing; 1995.
4. https://www.frontiersin.org/articles/10.3389/fimmu.2013.00185/full
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3936685/
6. https://pubmed.ncbi.nlm.nih.gov/11781377-nutrients-and-their-role-in-host-resistance-to-infection/
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162863/
11. https://pubmed.ncbi.nlm.nih.gov/11375434-vitamin-a-infection-and-immune-function/
12. https://pubmed.ncbi.nlm.nih.gov/9168553-vitamin-a-and-human-immunodeficiency-virus-infection/
