COVID-19: Four meta-analyses confirm vitamin D’s protective effect

Since December of 2021, two large meta-analyses have revealed that having low levels of vitamin D in your blood increases the risk of COVID-19 infections, severe disease, admission to intensive care, and death. A third meta-analysis has shown that only 12 percent of COVID-19 patients who took supplements of vitamin D were admitted to intensive care, compared to 26 percent of the non-supplemented. Finally, a fourth meta-analysis shows that supplementation with vitamin D significantly lowers the risk of life-threatening COVID-19 infections. This is particularly relevant during the winter period and among people at risk of being vitamin D-deficient, including groups such as seniors, people with dark skin, overweight people, and the chronically ill. There is an alarming need for increased focus on vitamin D supplements to prevent and treat COVID-19 and other virus infections by optimizing blood levels of the nutrient. It is also important to get plenty of magnesium, a nutrient the body needs to activate vitamin D.

Coronavirus is a family of RNA viruses that constantly mutate, and this limits the effect of vaccines. The most common coronavirus is the one that causes the simple cold. COVID-19 is a more recent variant that attacks the lower respiratory tract and can lead to bronchitis and pneumonia combined with fever. In most cases, COVID-19 develops mild to moderate symptoms or no symptoms at all. In severe cases, the immune system overreacts with cytokine storm and hyperinflammation that can cause acute respiratory distress syndrome (ARDS). This potentially life-threatening condition is the reason why the weakest patients succumb.
Most people who develop serious complications because of COVID-19 are above the age of 80 years or already suffer from comorbidities such as hypertension, diabetes, or other chronic diseases. A thing that both ageing and a variety of chronic diseases have in common is chronic low-grade inflammation in the body. It is therefore a weak and derailed immune defense that makes COVID-19 dangerous, not the coronavirus itself.

Vitamin D’s role in the immune defense

Vitamin D is considered a hormone. It regulates around 10 percent of our genes by way of different on-off switches that also include our highly-developed immune defense. Vitamin D is of vital importance to our innate immune system that handles most germs without us noticing. In our airways, we have many white blood cells (macrophages) and antibiotic peptides that need vitamin D to kill off virus. Our T cells, the special troops of our immune defense, also need vitamin D to help them divide explosively, attack virus, and establish effective immunity afterwards. If we lack vitamin D, we are much more vulnerable to infections. Also, a vitamin D deficiency may disrupt the communication between white blood cells, causing them to launch a cytokine storm and hyperinflammation, both of which make infections complicated and, in worst case, life-threatening.

Vitamin D’s therapeutic role in COVID-19

The first of the four meta-analyses (“Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-analysis”) was published on December 11th, 2021. The scientists wanted to study how vitamin D deficiency affected the severity and mortality of COVID-19. They also wanted to look at vitamin D’s therapeutic potential. The meta-analysis included 72 observational studies and 1,976,099 patients who were eligible for inclusion. Compared with patients who had plenty of vitamin D in the blood, those patients who lacked vitamin D had a:

• 1.46 times greater risk of getting COVID-19
• 1.9 times greater risk of serious complications
• 2.7 times greater risk of death

Because the studies had different ways of defining vitamin D deficiency and severe complications, it was difficult for the scientists to make proper comparisons. Nonetheless, the multitude of observational studies with nearly two million patients revealed that, not only does being vitamin D-deficient increase the risk of a COVID-19 infection, it also increases the risk of it becoming complicated and life-threatening. Apparently, more than half of those who died of COVID-19 lacked vitamin D.

Vitamin D status and COVID-19 severity

The other meta-analysis (“Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes”) was published on December 22th, 2021. Here, the researchers wanted to study if blood levels of vitamin D were related to severe COVID-19 symptoms (ARDS), admission to intensive care, and death. Their meta-analysis included 54 observational studies and 1,403,715 patients. Blood levels of vitamin D were categorized as:

• Insufficiency – less than 75 nmol/L
• Deficiency – less than 50 nmol/L
• Severe deficiency – less than 25 nmol/L

Seventeen of the 54 studies reported a relation between low vitamin D status and COVID-19 infection. Nine of the studies reported a relation between low vitamin D status and hospitalization. 27 of the studies reported a relation between low vitamin D status and admission to intensive care. The relation between the degree of vitamin D deficiency and the risk of being admitted to intensive care was as follows:

• Severe deficiency – 2.63 times higher risk
• Deficiency – 2.16 times higher risk
• Insufficiency – 2.83 times higher risk

The scientists conclude that in patients with low levels of vitamin D in their blood, the COVID-19 infection is more likely to develop into ARDS that requires admission to intensive care. The risk of dying of the infection is also much higher.

The effect of vitamin D supplements is convincing

The third study (“The Effect of Vitamin D Supplementation on Mortality and Intensive Care Unit Admission of COVID-19 Patients: Systematic Review, Meta-Analysis, and Meta-Regression”) was published in May, 2022. Six of the included studies involved 860 COVID-19 patients in intensive care. Three hundred and sixty-nine of the patients were given vitamin D, while 491 patients did not receive vitamin supplementation. Among the supplemented patients, 12 percent were admitted to intensive care, compared with 26 percent of the non-supplemented. In other words, supplementation more than halved the risk of being admitted to intensive care. All the data from the six studies revealed that vitamin D supplementation has a positive effect on the treatment of patients with severe COVID-19. It is, needless to say, essential to optimize blood levels of vitamin D as fast as possible, but the optimal vitamin D dose has not yet been established. In some studies, scientists have started by administering very high doses, while other studies have used supplements with calcidiol (25-hydroxyvitamin D3) that is both easier and faster for the body to absorb and utilize.

Vitamin D, COVID-19, severity, and mortality

The fourth and last meta-analysis (“Vitamin D and SARS-CoV-2 Infection, Severity and Mortality: A Systematic Review and Meta-analysis”) was published on July 6th, 2022, in PLoS One. Here, the researchers looked at levels of vitamin D in the blood and supplementation. The meta-analysis included 38 studies, two of which were randomized, controlled studies. The meta-analysis included more than 200,000 patients and showed that vitamin D supplementation was significantly related to a lower risk of severe COVID-19 complications and subsequent death. The scientists observed a particularly positive effect on older patients living at northern latitudes.

Vitamin D and comorbidities

The multitude of data shows that factors like old age, overweight, diabetes, hypertension, and other chronic illnesses make it more likely for COVID-19 to become complicated and life-threatening. As a result of the different comorbidities, patients die with – and not of – COVID-19. The scientists assume that being vitamin D-deficient is also a comorbidity. A host of studies show that ageing and the above-mentioned diseases are linked to chronic vitamin D deficiency.

Vitamin D supplementation and optimal utilization

The official recommendations for vitamin D call for daily intake of 5-20 micrograms, where the vulnerable groups should strive to have the highest intake. These are older recommendations that primarily aim at preventing osteoporosis. However, they are not guaranteed to provide the optimal vitamin D intake for immune defense and other body functions. It is therefore better to try to have optimal blood levels of vitamin D all year round and throughout life. According to leading scientists, the vitamin D blood level should lie in the range of 100-120 nmol/L.
There are different high-dosed vitamin D supplements that contain up to 100 micrograms of vitamin D and are perfectly safe to take. Make sure to get plenty of magnesium, as well. Different magnesium-dependent enzymes are needed for the body’s conversion of inactive cholecalciferol from sun exposure and supplements into the active form of vitamin D (1,25 dihydroxyvitamin D3). You make better use of your vitamin D supplement if you get plenty of magnesium from coarse and green foods or from supplements.
It takes some time for levels of vitamin D to reach their optimum in the blood and in cells. Also, beware that we are not able to synthesize vitamin D in the skin during the winter period, at least not at northern latitudes

Vitamin D’s mechanisms in relation to COVID-19

• Strengthens the innate immune defense that tackles germs without us noticing
• Strengthens the T cells that provide us with the best immunity against virus
• Strengthens the B cells that produce antibodies
• Regulates cytokines and inflammation
• Maintains the integrity of endothelial cells. Dysfunctional endothelial cells contribute to inflammation in the blood vessels and disruptions of the coagulation processes that are hallmarks of completed COVID-19 infections
• Increases the concentration of ACE2 (angiotensin-converting enzyme 2) that prevents virus from entering cells via the ACE2-receptors

References:

Harsha Anuruddhika Dissanayake et al. Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-analysis. The Journal of Clinical Endocrinology & Metabolism. 11 December 2021

Lacopo Chiodini et al. Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes. Frontiers 22. December 2021

Nikolaus Tentolouris et al. The effect of vitamin D supplementation on mortality and intensive care unit admission of COVID-19 patients. A systematic review, meta-analysis and meta-regression. Diabetes Metab. Res Rev. 2022 May

Constanza Gavioli et al. ” Vitamin D and SARS-CoV-2 Infection, Severity and Mortality: A systematic Review and Meta-Analysis. PLOS ONE. July 6, 2022

Mercola. Meta-Analyses Confirm Vitamin D Defends Against COVID. www.mercola.com. September 05, 2022

Mohsen Nabi-Afjadi et al. The effect of vitamin D, magnesium and zinc supplements on interferon signaling pathways and their relationship to control SARS-CoV-2 infection. Clinical and Molecular Allergy. 2021

Daniel Chauss et al. Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells. Nature Immunology. 2021

Purdue University. Researchers study the link between vitamin D and inflammation. ScienceDaily 2021.

Krishna Sriram et al. What is the ACE2 receptor, how is it connected to coronavirus and why might it be key to treating COVID-19? The Conversation. 2020

Qi Dai et al. Magnesium status and supplements influence vitamin D status and metabolism: results from a randomized trial. The American Journal of Clinical Nutrition. 2018

Nikki Hancocks. Diet and supplements: Swiss panel publishes COVID-19 recommendations. 2020