Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

Nutrients

APRIL 2, 2020; VOL. 12; NO. 4

William B. Grant, Henry Lahore, Sharon L. McDonnell, Carole A. Baggerly, Christine B. French, Jennifer L. Aliano, Harjit P. Bhattoa. This study cites 157 references.

BACKGROUND:

Neither UVB from the sun or supplemental vitamin D3 are the active form of vitamin D; both forms require a healthy liver and healthy kidneys to make the active form, 1, 25-dihydroxy vitamin D:

STEP #1

Our skin cells contain a molecule called 7-dehydrocholesterol (provitamin D3) which absorbs ultraviolet light B (UVB, wavelength 290-319 nm)

STEP #2

The absorption of UVB by provitamin D3 produces pre-vitamin D3 within the skin cells

STEP #3

Our body heat converts pre-vitamin D3 into vitamin D3 within the skin cell

(this is the same molecule as supplemental vitamin D3 )

STEP #4

Vitamin D3 exits the skin cell into the blood stream and travels to the liver where 25-hydroxy vitamin D (calcidrol) [25(OH)D] is produced

(this is what is measured in a standard blood vitamin D testing )

STEP #5

25-hydroxy vitamin D [25(OH)D] leaves the liver via the blood stream to the kidney

STEP #6

The kidney makes the active form of vitamin D 1, 25 dihydroxy vitamin D

STEP #7

This active form of vitamin D (1, 25 dihydroxy vitamin D) circulates throughout the body, binding to receptors in the nucleus of the cell influencing gene expression

“The seasonality of many viral infections is associated with low 25(OH)D concentrations, as a result of low UVB doses owing to the winter in temperate climates and the rainy season in tropical climates.”

••••••••••••••••••••

“This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk.”

KEY POINTS FROM THIS ARTICLE:

1) “The world is now experiencing its third major epidemic of coronavirus (CoV) infections.”

• A new CoV infection epidemic began in Wuhan, Hubei, China, in late 2019.

• Severe acute respiratory syndrome (SARS)-CoV, started in China in 2002.

• Middle East respiratory syndrome (MERS)-CoV, was first reported in 2012.

2) “The direct cause of death is generally due to ensuing severe atypical pneumonia.”

3) “Through several mechanisms, vitamin D can reduce risk of infections,”

including:

• “Cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines.”

4) “Evidence supporting the role of vitamin D in reducing risk of COVID-19

includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest.”

5) Vitamin D deficiency contributes to acute respiratory distress syndrome.

6) “Case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration.”

7) The authors city 9 published reviews pertaining to the ways in which vitamin D reduces the risk of viral infections.

• “Vitamin D has many mechanisms by which it reduces the risk of microbial infection and death.”

8) Vitamin D reduces the risk of infection through 3 mechanisms:

• Physical barriers, the junctions:

•• Viruses disturb junction integrity, increasing infection by the virus and other microorganisms.

•• Vitamin D helps maintain tight junctions, gap junctions, and adherens junctions.

• Vitamin D enhances cellular innate (natural) immunity by induction of antimicrobial peptides: cathelicidin and defensins.

•• Cathelicidins exhibit direct antimicrobial activities against a spectrum of microbes, including bacteria, viruses, and fungi.

•• These “host-derived peptides kill the invading pathogens by perturbing their cell membranes and can neutralize the biological activities of endotoxins.”

• Vitamin D enhances adaptive (cellular) immunity.

•• This reduces the cytokine storm induced by the innate immune system.

9) Vitamin D reduces the production of pro-inflammatory cytokines and increases the expression of anti-inflammatory cytokines by macrophages.

10) “Serum 25(OH)D concentrations tend to decrease with age, which may be important for COVID-19 because case-fatality rates (CFRs) increase with age.”

• Older persons spend less time in the sun.

• Older persons have lower levels of 7-dehydrocholesterol in the skin.

• Some pharmaceutical drugs reduce serum 25(OH)D concentrations, including, anti-epileptics, anti-neoplastics, anti-biotics, anti-inflammatory agents, antihypertensives, anti-retrovirals, and endocrine drugs. [Very Important]

11) Vitamin D supplementation can enhance endogenous antioxidation by increasing glutathione production.

• “The increased glutathione production spares the use of ascorbic acid (vitamin C), which has antimicrobial activities, and has been proposed to prevent and treat COVID-19.”

12) “A former director of the Center for Disease Control and Prevention, Dr. Tom Frieden, proposed using vitamin D to combat the COVID-19 pandemic on 23, March 2020.”

13) “Studies suggest that raising 25(OH)D concentrations through vitamin D supplementation in winter would reduce the risk of developing influenza.”

14) A study of 198 healthy adults examined the relationship between serum 25(OH)D concentration and incidence of acute RTIs (ARTIs):

• Maintaining 25(OH)D >38 ng/mL throughout the study was “associated with a significant twofold reduction in risk of developing ARTIs and with a marked reduction in the percentage of days ill.” [Important]

15) Other nutrients (in addition to vitamin D) associated with good health, were vitamin C, omega-3 fatty acids, and magnesium. [Important]

16) “Previous work suggested that higher UVB doses were associated with higher 25(OH)D concentrations, leading to reductions in the cytokine storm and the killing of bacteria and viruses that participate in pneumonia.”

17) The authors cite historical studies that suggest that darker skinned persons have much higher mortality rates and higher rates of chronic diseases than lighter skinned persons and suggest the disparity is at least partially linked to lower levels of vitamin D [melanin pigmentation reduces skin vitamin D synthesis].

18) A 2016 vitamin D3 trial in ventilated intensive care unit patients found:

Controls Supplemented w 250,000 IU Supplemented w 500,000 IU

25(OH)D Levels 21 ng/mL 45 ng/mL 55 ng/mL

Days in the Hospital 36 Days 25 Days 11 Days

19) “Vitamin D supplementation to raise serum 25(OH)D concentrations can help reduce hospital-associated infections.”

• “Concentrations of at least 40–50 ng/mL (100–125 nmol/L) are indicated on the basis of observational studies.”

• “Although the degree of protection generally increases as 25(OH)D concentration increases, the optimal range appears to be in the range of 40–60 ng/mL (100–150 nmol/l).”

• “From the literature, it is reasonable to suggest taking 10,000 IU/d for a month, which is effective in rapidly increasing circulating levels of 25(OH)D into the preferred range of 40–60 ng/mL.”

•• “To maintain that level after that first month, the dose can be decreased to 5000 IU/d.”

• “When high doses of vitamin D are taken, calcium supplementation should not be high to reduce risk of hypercalcemia.” [Important]

• “During the COVID-19 epidemic, all people in the hospital, including patients and staff, should take vitamin D supplements to raise 25(OH)D concentrations as an important step in preventing infection and spread.” [Very Important]

20) “Vitamin D3 supplementation should be started or increased several months before winter to raise 25(OH)D concentrations to the range necessary to prevent acute respiratory tract infections (ARTIs).”

21) Patients who received 10,000 IU/d for a year, mean concentrations increased from 25 to 96 ng/mL. “No cases of vitamin D–induced hypercalcemia were reported.”

22) “Although 20 ng/mL seems adequate to reduce risk of skeletal problems and ARTIs, concentrations above 30 ng/mL have been associated with reduced risk of cancer, type 2 diabetes mellitus, and adverse pregnancy and birth outcomes.”

• “On the basis of the findings in several studies discussed here, as well as recommendations for breast and colorectal cancer prevention, the desirable concentration should be at least 40–60 ng/mL.”

23) “The U.S. Institute of Medicine noted that no adverse effects of vitamin D supplementation had been reported for daily doses <10,000 IU/d.”

24) Groups of people who were likely to have low concentrations of vitamin D and could benefit from higher concentrations include:

• Pregnant women

• The obese

• People with chronic diseases

• The elderly

25) For about half the population, taking 5000 IU/d of vitamin D3 would raise 25(OH)D concentration to 40 ng/mL.

• “Taking 6,235–7,248 IU/d as proposed to ensure that 97.5% of the population has concentrations >20 ng/mL would not exceed the 10,000-IU/d threshold.”

26) “Vitamin D supplementation is required for many individuals to reach 25(OH)D concentrations above 30 ng/mL, especially in winter.”

• “Daily or weekly vitamin D supplementation is recommended, as is the annual determination of serum 25(OH)D concentration for those with health risks.”

27) “Magnesium supplementation is recommended when taking vitamin D supplements. Magnesium helps activate vitamin D, which in turn helps regulate calcium and phosphate homeostasis to influence the growth and maintenance of bones.” [Very Important]

• “All the enzymes that metabolize vitamin D seem to require magnesium,

which acts as a cofactor in the enzymatic reactions in the liver and kidneys.”

• “The dose of magnesium should be in the range of 250–500 mg/d.”

27) “A recent review stated: ‘Although contradictory data exist, available evidence indicates that supplementation with multiple micronutrients with immunesupporting roles may modulate immune function and reduce the risk of infection’.”

• “Micronutrients with the strongest evidence for immune support are vitamins C and D and zinc.” [Key Point]

28) “To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d.” [Key]

• “The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL

(100–150 nmol/L).” [Key Point]

• “For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful.”

COMMENT FROM Dr. MacDonald:

I have reviewed many articles pertaining to vitamin D status and Immunology, pain, dementia, autism, and disc degeneration. My previous blog post was specifically on Vitamin D and Covid-19:

Vitamin D and Inflammation: Implications for Severity of Covid-19

This article supports supplementing to improve host health with:

Vitamin D3, about 5,000-10,000 daily

Magnesium, about 250-500 mg daily

Omega-3s. about 3000 mg daily of EPA + DHA

Vitamin C

Zinc

And our final thought, the authors specifically state:

To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D 3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D 3 doses might be useful”.

As always, this blog post does not constitute medical advise, nor does it establish a doctor/patient relationship. This is informational based on a current literature review of published peer reviewed medical literature.