The coronavirus disease 2019 (COVID-19) has become a global pandemic and severely affected our everyday life. At this time, there is yet any clinically proven drugs or treatments to prevent or cure COVID-19.
With the novel coronavirus, about 80% of the infected had mild to moderate symptoms (mild symptoms up to mild pneumonia), about 15% developed severe disease (shortness of breath, low blood oxygen, or >50% lung involvement), and 5% became critically ill (respiratory failure, shock, or multi organ dysfunction).
Patients with severe COVID-19 illness and adverse outcome are mostly older, have diabetes, heart disease, prior stroke, hypertension, chronic respiratory disease, and/or chronic lung disease. In many cases, these patients’ immune system, in an attempt to fight the virus, becomes dysfunctional and go into overdrive, resulting in a deadly effect known as a “cytokine storm”.
Cytokines are an important part of your immune response. Your body release them as a response to an infection to trigger inflammation for your protection. A cytokine storm happens when the body releases excessive or uncontrolled levels of cytokines, causing hyper inflammation, which may lead to serious complications and even death.
Why does the immune system go haywire? How come it occurs more in patients who are immunocompromised or with preexisting conditions? How can we have a stronger, better functioning immune system?
By now, most of us are well aware of the important role nutrients like vitamin D, vitamin C, zinc, and probiotics play in regulating the immune system and keeping us healthy. Not enough has been said about vitamin A though.
For the past several decades, scientists have been studying the impact of dietary vitamin A on human health. It is well established that vitamin A is an essential nutrient and is responsible for many vital functions in the body:
- It protects the eyes from night blindness and age-related decline.
- It reduces the risk of certain cancers.
- It supports a healthy immune system.
- It reduces the risk of skin problems like eczema and acne.
- It supports bone health.
- It promotes healthy growth and reproduction.
In the following, we will look at how vitamin A can help reduce the incidence and severity of infectious diseases, how the immune system works against infectious agents like viruses, and the role vitamin A plays in regulating a healthy immune response. Lastly, we will discuss how you can get enough vitamin A to complement your immune protocol.
Understanding Vitamin A
Vitamin A is a group of compounds found in both animal and plant foods. It comes in two forms: preformed vitamin A and provitamin A carotenoids.
- Preformed vitamin A is known as the active form of the vitamin, which the body can readily use. It is fat-soluble and found in animal foods, like liver and eggs, and includes retinoid compounds like retinol, retinal, and retinoid acid.
- Provitamin A carotenoids include carotenes (like alpha-carotene and beta-carotene) and xanthophyll (like astaxanthin, lutein, and zeaxanthin). These are the inactive form or precursors of the vitamin found in plants such as sweet potatoes and carrots. These compounds are water-soluble and have to be converted to the active form before the body can use it. For example, beta-carotene is converted to retinol in the small intestine. However, the ability to convert provitamin A into the active form is impaired in many people. More on this later.
Vitamin A Reduces Incidence And Severity Of Infectious Diseases
Research studies over the past several decades have well established the beneficial effect of vitamin A on infectious diseases.
- It was dated back to the ancient Egyptians that vitamin deficiency and disease were first correlated. They applied liver (which is rich in vitamin A) extracts to the eyes of people affected by nutritional night blindness.
- In 1892, it was suggested that diet could have an impact on susceptibility to infectious diseases based on the observation that children suffering from measles or whooping cough also developed blindness produced by vitamin A deficiency.
- Later studies indicated that supplements with carrots (which are rich in beta-carotene) could reduce the number and severity of respiratory infections.
- More recent studies have shown that deficiency of vitamin A is associated with heightened incidence of infectious diseases, including respiratory diseases, malaria, tuberculosis, HIV and others.
- Studies showed that high dose vitamin A supplementation in children with measles increased the number of circulating T cells (a type of immune cells), and also that vitamin A supplementation could reduce the incidence of respiratory infections in children.
How The Immune System Works
Our immune system can be broken down into the innate immune system and the adaptive immune system.
Innate immune system
This is the dominant defense system in the body and it relies on the use of physical barriers like the skin and mucous membranes, coupled with first responder defenders called leukocytes (white blood cells). Leukocytes include phagocytes (which engulf foreign invaders) and natural killer cells.
The innate immune system response is why you get a stuffy nose and sneeze when you have a cold, or why a scrapped knee gets red, hot, and inflamed, or filled with pus. For people who contract COVID-19 and have no symptoms or only mild symptoms, their innate immune system is effective and working well against the coronavirus.
Adaptive immune system
When the innate immune system is not strong enough to combat the foreign invaders, it sends out signals called antigens to call on the second line of defense – the adaptive immune system. This system uses special types of leukocytes called lymphocytes, namely the B-cells and T-cells.
This is typically when the inflammatory response gets kicked into a higher gear and you develop a fever and body aches. The adaptive immune response not only identifies and fights off viruses, it also remembers them so it can quickly and effectively combat and neutralize them in the future, thus creating immunity. This is also how vaccines work.
COVID-19 And Cytokine Storms
The coronavirus tends to target the respiratory system by attaching and infiltrating the lung cells where it can more effectively hide from the immune system and reproduce. The infected cell will then produce more of the coronavirus and the process repeats itself.
When the immune system detects this, it kicks off its response. The T-cells are then activated and they release cytokines. A cytokine is a hormone of the immune system. The body produces cytokines to help fight bacteria, viruses, and other invading organisms. Cytokines can be pro-inflammatory when they attract white blood cells to the site of an infection. Cytokines can also be anti-inflammatory when they try to ramp down an immune response once the threat has been neutralized.
The release of cytokines triggers additional T-cells to be made, which then release even more cytokines. One type of T-cells called cytotoxic T-cells roam the body and kill infected cells. When the immune system is working well, the cytotoxic T-cells only target infected cells to be killed and move along.
A cytokine storm happens when the immune system goes haywire. This is when the body’s immune response gets so amped up that it stops differentiating between infected and healthy cells. In other words, the lung cells are now attacked by both the coronavirus as well as the immune system.
With COVID-19, the cytokine storm focuses on the lungs, causing acute respiratory distress syndrome (ARDS) and damage to the walls and lining cells of the alveoli (air sacs) in the lungs.
Normally, the wall of the alveolus is super thin, so oxygen can easily get from the air space in between into the red blood cells. In this case, both the wall and lining cells as well as the capillaries are destroyed. The debris that accumulates from all that damage lines the wall of the alveolus. The damage to the capillaries also causes them to leak plasma proteins that add to the wall’s thickness. Eventually the wall becomes so thick that it is hard to transfer oxygen, hence, the feeling of shortness of breath.
Many people who get ADRS need help breathing from a ventilator. As fluid collects in the lungs, they carry less oxygen to the blood. That means your blood may not supply your organs with enough oxygen to survive, resulting in the lungs, liver, and kidneys to shut down and stop working.
Additionally, doctors found that once the coronavirus gets to the lungs, it may travel to the bloodstream and infect the endothelium, lining of the blood vessels, causing endotheliitis. It is, therefore, no surprise that people who have conditions like high blood pressure, diabetes, and heart disease that put a lot of stress on the endothelium are also the ones who get the sickest when they catch the coronavirus.
COVID-19 does not merely cause lung problems. Many severe patients also develop widespread blood clots as a result of the hyper-inflamed state of cytokine storm, leading to strokes, heart attacks, and organ failure. What’s more, doctors have noted an alarming trend as they treat more and more COVID-19 stroke patients who are in their 30s and 40s without risk factors. These people are at least 15 years younger than usual stroke patients without the virus.
Vitamin A Regulates Immune Responses
The effect of vitamin A on immune function is wide-reaching:
- It promotes and regulates both the innate and adaptive immune systems and the development of healthy immune responses.
- It plays an important role in the regulation of different white blood cells (neutrophils, monocytes, macrophages, natural killer cells, and lymphocytes) and influence the generation of cytokines by the immune cells.
- Deficiency of vitamin A favors the production of more pro-inflammatory cytokines.
- Research on vitamin A deficiency in children found that it damages the mucosal barrier, which is the natural defense of the respiratory tract, allowing bacteria and viruses to proliferate.
Are You At Risk For Vitamin A Deficiency?
Vitamin A deficiency may lower your immune function, thereby raising your risk of complications from infectious diseases.
A blood test can determine if you are severely vitamin A deficient. Vitamin A is stored in the liver. Normally, the body will always try to maintain a healthy blood vitamin A concentration (a process called homeostatic regulation). However, when the body’s reserves of vitamin A are significantly compromised, vitamin A concentration in the blood can drop below normal range.
Signs of mild deficiency
- dry eyes
- poor night vision
- hormonal imbalances
- irregular periods
- vaginal dryness
- low energy and fatigue
- mood disorders
- frequent throat and chest infections
- bumpy skin
- eczema and acne
- thyroid dysfunction
Strict vegans who avoid all animal-based foods and alcoholics are more prone to vitamin A deficiency.
Since vitamin A is stored in the liver, and alcoholics may have existing liver damage, they may be more susceptible to deficiency.
Vegans who rely entirely on plant sources of the precursor to vitamin A need to have the carotenoids converted to retinol, the active form of Vitamin A. However, in a majority of people, the carotene-to-retinol conversion is severely compromised, and in some it may even be as low as 10%.
Factors that inhibit the conversion include:
- genetic variants in the BCO1 gene that impact the conversion of beta carotene
- alcohol use
- certain medications
- toxic exposures
- medical conditions that interfere with the digestion of fat (including Crohn’s disease, Celiac disease, cystic fibrosis, pancreatic enzyme deficiency, and gallbladder and liver disease)
- a low-fat diet – as healthy fats are needed for the efficient conversion of carotenoids to retinol
Sources Of Dietary Vitamin A
From animals (preformed vitamin A):
- Pastured animal liver (liver is an organ that processes toxins, toxins are not stored in the liver but in fats in the body)
- Pastured poultry giblets
- Cod liver oil
- Grass fed ghee and butter
- Grass fed cream and cheese
- Pastured egg yolks
- Sockeye salmon
From plants (provitamin A carotenoids):
- Sweet potato
- Winter squash
- Dark green, leafy vegetables
- Red bell peppers
Vitamin A Supplementation
Ideally, it is best to eat vitamin A-rich animal foods regularly. There is no risk of excessive intake through food. The risk lies in taking mega dose supplements. Symptoms of vitamin A toxicity include changes to vision, bone pain, and skin changes. Chronic toxicity can lead to osteoporosis and liver damage.
Do note that blood vitamin A levels (as indicated in a blood test) may not indicate changes in supplementation because for healthy people blood vitamin A concentrations are always under homeostatic regulation and will stay within normal range. At present, there are no non-invasive ways (requires liver biopsies) to accurately measure the amount of vitamin A stored in the body.
For people who would like to take vitamin A supplements, the Recommended Daily Allowance (RDA) for adult male is 3,000 I.U. (or 900 mcg) and adult female is 2,300 I.U. (or 700 mcg).
The Upper Tolerable Intake Level (UL) is 10,000 I.U. (or 3,000 mcg) daily.
Always take it with food containing fats for optimal absorption.
Remember that vitamin A is available in two different forms: preformed vitamin A and provitamin A carotenoids. The maximum daily dose of 10,000 I.U. per day relates to only preformed vitamin A.
Some supplements contain vitamin A in both preformed and provitamin A carotenoids forms. For these supplements, the amount of preformed vitamin A should be used to determine if the amount of vitamin A is safe.
In some cases, a vitamin A supplement with vitamin A in amounts greater than 10,000 I.U. may still be safe if a portion of the vitamin A is in the provitamin A carotenoids. For example, a supplement containing 23,000 I.U. of vitamin A, of which 60% is provitamin A carotenoids, will still be safe. This is because only 40% of the vitamin A content, or 9,200 I.U., is preformed vitamin A.
Preformed vitamin A may come in two forms – from retinyl palmitate (in tablets) and/or from cod or other fish liver oil (in soft gels). Check the ingredients if you have allergies towards fish or soy.
- If you are pregnant, may become pregnant, or breastfeeding, keep the daily limit to 5,000 I.U.
- If you have a disorder that affects fat absorption, you may not be able to absorb vitamin A properly.
- Do not take vitamin A if you have a type of high cholesterol called Type V Hyperlipoproteinemia.
- Do not take vitamin A if you have liver disease.
- Iron deficiency may affect the body’s ability to breakdown and use vitamin A.
- People with severe protein malnutrition may end up with too much vitamin A in the body.
- People with zinc deficiency may need to take both vitamin A and zinc to improve the condition.
- Use caution if you are taking medications for skin conditions (Retinoids) as they may interact with vitamin A.
- If you are taking antibiotics, do not take a high dosage of vitamin A.
- Medications that harm the liver (hepatotoxic drugs) interacts with vitamin A.
- Warfarin (Coumadin) interacts with vitamin A.
Although nutrients like vitamin A, vitamin D, vitamin C, zinc, and probiotics have been shown to strengthen the immune system, at present, there is no research or study on their efficacy towards preventing and curing COVID-19.