Vitamin D supplementation of critically ill patients can save lives

Many critically ill patients lack vitamin D to an extent that can be life-threatening. This also goes for patients hospitalized with COVID-19. A large meta-analysis concludes that supplementation with vitamin D can lower all-cause mortality and reduce the duration of patients’ stay in intensive care. In the meta-analysis, the researchers look at the mechanisms that enable vitamin D to regulate inflammation and oxidative stress, which can lead to organ failure in critically ill patients.

The effect of giving vitamin D supplements to critically ill patients has remained unclear due to differences in treatment methods and their outcome. In a new meta-analysis that is published in Critical Care, a group of scientists wanted to study the effect of giving supplements of various forms of vitamin D to patients with critical disease. They trawled through various databases and ended up including 16 clinical studies with a total of 2,449 patients. The patients were given vitamin D in different ways – orally, intravenously, through intramuscular injections, or enterally.
Vitamin D supplementation had the following effect:

• It lowered all-cause mortality by 30 percent
• It reduced the duration of intensive care by 70 percent
• It reduced the time spent on ventilators by 54 percent

Moreover, intravenous vitamin D supplementation was superior to enteral vitamin D supplementation when it came to reducing mortality in general.
The scientists conclude that vitamin D supplementation given to critically ill patients can reduce the time they spend in intensive care, including the time spent on a ventilator. Also, vitamin D supplementation lowers the risk of dying. The scientist also concluded that intravenous vitamin D has a better effect than enteral vitamin D for improving survival.
Moreover, the scientists mention that oral intake of vitamin D in the form of calcifediol (25(OH)D) is a promising alternative because this form of the nutrient is easier to absorb and utilize. Calcifediol is also the form of vitamin D that is measured in blood tests. Some studies have been made with rather large doses of intravenously administered calcifediol for a faster effect.
The type of vitamin D that we synthesize when we are exposed to sunlight or take in supplement form is called cholecalciferol. The liver must convert this form into calcifediol, which is then converted into the active steroid form of vitamin D called calcitriol. This conversion takes place in the kidneys, the immune cells, and various other places. Many older people and people with illnesses have difficulty with absorbing and utilizing cholecalciferol and therefore benefit more from calcifediol, which they can absorb and activate much faster.

How does vitamin D affect critically ill patients?

Dysfunctions in the immune system, inflammation, and oxidative stress er all important factors in the development of critical illness and can eventually result in organ failure and death. Most chronic diseases are actually associated with chronic low-grade inflammation that causes oxidative stress, which is an imbalance between harmful free radicals and protective antioxidants. Oxidative stress causes free radical damage to tissues like the circulatory system and various organs.
People who suffer from chronic low-grade inflammation are more vulnerable to different infections, including COVID-19. A derailed immune defense tends to overreact by launching cytokine storm and hyperinflammation in the endothelial cells of the lungs, causing acute respiratory distress syndrome (ARDS). Dangerous hyperinflammation can also occur in the epithelial cells of the blood vessels and in other organs, leading to circulatory failure and death.
Blood poisoning, which is one of the major cases of death, is also associated with cytokine storm and hyperinflammation.
It is the derailed immune defense, inflammation, and oxidative stress that are the actual cause of most chronic diseases, blood poisoning, and potentially lethal COVID-19 infections, and the authors therefore point to vitamin D’s importance for a well-functioning immune defense that can handle infections in a normal fashion without overreacting. Vitamin D regulates inflammatory processes and shuts them down before they get out of hand and cause damage to blood vessels and organs. According to the study authors, vitamin D has the following protective roles in connection with COVID-19:

• It regulates cytokine storm
• It regulates the activity of neutrophilic granulocytes (a type of white blood cells)
• It helps maintain the pulmonary epithelial barrier
• It stimulates the body’s repair of damaged epithelial cells

The also refer to a number of different studies where calcifediol (25(OH)D) administered to critically ill COVID-19 patients reduced their need for intensive care admission, ventilator use, and mortality risk.

Dose and timing of vitamin D plays a major role

Although the results of intravenous and intramuscular vitamin D supplements look promising, there is still some uncertainty when it comes to finding the optimal dose. This must be clarified with future studies. Intravenous therapy with high doses of vitamin D is especially relevant for patients with severe vitamin D deficiency, who do not respond to oral intake of the nutrient.
Also, there is some uncertainty with regard to intramuscular vitamin D therapy, which may be a problem for patients on blood thinners.
The scientists see a much greater potential in using oral supplementation with calcifediol because it is easy for the body to absorb, even for people with impaired intestinal absorption of nutrients.
The timing of vitamin D supplementation is also vital because it takes around 2-3 day to convert inactive calcifediol into active calcitriol, the steroid form of vitamin D.
Vitamin D supplementation should ideally be initiated as soon as a patient is admitted to intensive care and preferably within 14 hours. That way, the active form of vitamin D can dial down the life-threatening cytokine storm and hyperinflammation in the critical phase – before it’s too late.

Reference:

Administration of vitamin D and its metabolites in critically ill adult patients: an updated systematic review with meta-analysis of randomized controlled trials. Critical Care volume 26, Article number: 268 (2022)