Vitamin D and Influenza

Should I take vitamin D to reduce the risk of colds and flu (URI)?

Yes, you should because so many studies show that vitamin D helps reduce the risk of colds and flu. The best dose to use is unknown, but the Vitamin D Council recommends that adults take 5,000 to 10,000 IU per day, depending on body weight.

Children should take at least 100 IU/kg/day. However, there is a wide variation in human response to any one vitamin D dose so, after taking vitamin D for a few months, it is important to have your vitamin D blood level checked to make sure it is > 40 ng/ml. The Vitamin D Council offers a convenient in-home vitamin D blood spot kit or your doctor can order the test.

The Vitamin D Council recommends vitamin D to help prevent colds and flu (URI or upper respiratory infections) based on the findings of two large meta-analyses (the strongest proof in medicine) published in respected medical journals. For example, Bergman et al analyzed 11 placebo controlled trials involving 5,660 subjects and found that those taking a daily dose of vitamin D had half the risk of developing a URI.[1] Many of the studies they analyzed used very low doses of vitamin D, meaning the overall effect may be greater with an adequate dose.

In another meta-analysis, Martineau et al  analyzed 25 randomized controlled trials (most reliable type of study) involving 11,320 subjects, and found that vitamin D reduced the risk of developing a URI.[2] Even those subjects with very low vitamin D levels experienced 1/3 the risk when supplementing with vitamin D compared to those who did not take any vitamin D. Like the study above, Matineau et al found daily dosing to be the most effective.

Regarding children, a recent study of 400 infants found that influenza A infection was much more common among infants taking 400 IU/day compared to infants given 1,200 IU/day.[3].

Should I take high doses of vitamin D for ten days if I get a URI?

There is simply no data on this question. If you decide to take vitamin D to treat a URI, 50,000 IU/day for ten days is certainly safe.

What is influenza?

Influenza, also known as the flu, is a contagious respiratory infection caused by the influenza virus that infects the nose, throat and lungs. In the United States, peak flu season is from late November through March, but flu season can last through May. Young children, the elderly and people with chronic diseases are more likely to have serious complications after getting the flu. Influenza infections can require hospitalization or even death in serious cases.[4] In 1918, the flu killed 50 million people worldwide and nothing, including modern anti-virals or flu shots, can prevent this from happening again. It is just a matter of time.

Since the common influenza virus changes every season, so does the vaccine but, even so, the vaccines are of marginable effectiveness. The severity and prevalence of the flu changes each season. The flu shot is based on a guess about which three strains are likely to be active in any one year, and the experts often guess incorrectly.

The three types of influenza that affect humans are A, B and C, however types A and B are typically responsible for seasonal influenza epidemics. Type C influenza viruses can cause a mild respiratory infection, but do not cause flu epidemics. There are also subtypes of type A influenza viruses based on two proteins found on the virus, abbreviated H and N. For example, H1N1 is usually very common, however the most common influenza virus during the 2016-2017 flu season was H3N2.

What are the symptoms of influenza?

A person infected with the influenza virus may experience some or all these symptoms:[5]

• Fever or chills
• Cough
• Sore throat
• Muscle, body and head aches
• Fatigue
• Vomiting and diarrhea, which is more common in children with influenza.
• Prostration or the need to lie down. (This clinical sign helps differentiate colds from flu. For example, in 1918 prostration after infection was so common among GIs in France that they called it the “knock-me-down fever.”)

A healthy person will normally recover from influenza in a few days to less than two weeks, although some may develop serious complications from influenza, such as pneumonia, bronchitis, or sinus and ear infections. Influenza can also make a chronic condition, such as asthma, worse. When influenza is fatal, the death is usually due to a bacterial infection, such as pneumonia, that is secondary to the influenza.[6]

What are the risk factors for influenza?

Annually, influenza affects about one-tenth the U.S. population.[7] During the 2016-2017 flu season, more than half of hospitalizations related to influenza were in adults over the age of 65.

On average, about 10% of the U.S. population will get the flu each year.[8] However, during the AH1N1 pandemic of 2009-10, the number of cases rose to 95,000 or 20%.[9]

• Between 30,000 to 100,000 adults are hospitalized each year in the U.S. because of flu complications.[10]
• In the 30-year period from 1976 to 2006, as low of 3,000 and as high of 49,000 people died each year from flu-related causes in the U.S., although some experts believe that most excess wintertime deaths are due to the flu.

People who are at higher risk for developing influenza include:[11]

• People over age 65
• Children, especially those under age two
• People with chronic diseases, such as asthma, diabetes, lung or heart disease
• People with weakened immune systems, such as those with cancer or HIV/AIDS
• People who are morbidly obese
• Pregnant women
• American Indians and Alaskan natives

It is important to note that many people with these risk factors are also vitamin D deficient.

How does influenza spread?

A person infected with the influenza virus can be contagious one day before symptoms develop and up to seven days after they become sick. Young children and people with compromised immune systems can infect others for a longer period of time.[12]

It is widely thought that the influenza virus can spread when an infected person coughs, sneezes or speaks, but this has never been proven. Droplets holding the influenza virus are thought to travel through the air and can be directly inhaled by another person through the mouth or nose. The droplets may also land on a surface where they can be picked up by someone else who is in turn infected when they touch their eyes, nose or mouth.[13]

However, all six attempts to prove that respiratory infections are transmitted person-to-person or sick-to-well have failed. Also, other characteristics of influenza continue to puzzle scientists, and a decision to not take vitamin D during flu season is a kind of Pascal’s Wager with influenza.

The peak influenza season is near the end of the year in the northern hemisphere, a time when it is coldest and the air is driest. This climate allows the influenza virus to live outside of the human body for an extended period.[14]

Once an individual has had influenza, their body creates antibodies to help protect against that specific virus in the future. However, because influenza viruses change from year to year, these antibodies will not fight off newer virus strains. Vaccines only help the human body make antibodies against the current influenza virus.[15]

What is the link between influenza and vitamin D?

Vitamin D is an important factor in immune system health. Some studies have shown a link between vitamin D status and the risk of developing influenza. People with low vitamin D levels may have an increased risk of developing influenza.[16]

Vitamin D receptors are found on the surface of a cell where they receive chemical signals. By attaching themselves to a receptor, these chemical signals direct a cell to do something, for example, to act in a certain way, or to divide or die.

There are vitamin D receptors found on cells in the immune system, and vitamin D can bind to these receptors.[17] Vitamin D works in the immune system by reducing levels of inflammatory proteins called cytokines, as well as increasing the amount of antimicrobial proteins, which are naturally occurring antibiotics that destroy invading germs and viruses. This combination of lowering inflammation and increasing antimicrobial defenses can help an individual’s immune system fight infections more effectively.[18],[19] These actions also reduce the risk of developing pneumonia, which is the primary complication of influenza that can result in death.[20]

There are two branches of the immune system: adaptive and innate. The adaptive immune system develops based on previous exposure to a virus. The innate immune system responds quickly to foreign invaders, and its effectiveness is determined by the levels of immune cells and proteins an individual has.[21] Low vitamin D levels result in some aspects of the innate immune system not functioning as well as they should.[22]

Influenza epidemics occur in the winter when vitamin D levels in the greater population are dramatically lower.[23] Considering the seasonal nature of influenza, vitamin D might be a factor affecting someone’s chances of getting the flu, a theory first proposed by Cannell in 2006.[24]

What does the research say in general about influenza and vitamin D?

Preventing influenza

Most studies about influenza have shown that people with lower levels of vitamin D are more likely to get the flu. One study looked at the levels of vitamin D in people with prostate cancer and their immune response to the influenza vaccine. The study found that people with higher levels of vitamin D had an improved response to the vaccine, meaning that they would be more protected against getting influenza.[25] However, another study evaluated vitamin D and influenza in people over age 50 , and found that vitamin D levels didn’t have a significant effect on their immune response to the influenza vaccine.[26]

A study comprised of healthy adults found that people with lower levels of vitamin D were twice as likely to develop influenza, compared to people with high levels of vitamin D.[27]

Treating and recovering from influenza

Some research has shown a relationship between vitamin D status and the duration of the influenza infection. Other studies have looked at influenza outcomes, such as pneumonia or death, in large influenza epidemics in the past.

A study that looked at deaths associated with the large 1918-1919 influenza pandemic found that the lowest influenza-related death rates in the United States were in the city with the highest amounts of UVB light, which helps the body make vitamin D. They also found that the highest number of influenza deaths were in the city with the lowest amounts of UVB radiation.[28]

People with enough vitamin D may recover from influenza faster than people with low levels of vitamin D. One study found that people with vitamin D levels above 38 ng/ml recovered from influenza in an average of two days; whereas people with vitamin D levels below 38 ng/ml took an average of nine days to recover from influenza.[29]

What does recent research say about vitamin D and influenza?

An experiment conducted in the United States gave elderly African-American women 800 IU of vitamin D per day for two years and then 2,000 IU per day for the third year. The control group was given a dummy pill. The researchers looked at how many times those women got influenza over the three-year period and found that:[30]

• The vitamin D group had fewer influenza symptoms compared to the dummy pill group.
• Only one person in the vitamin D group contracted influenza when taking 2,000 IU per day, compared to 30 cases of influenza or colds for those taking the dummy pill.
• The dummy pill group had influenza symptoms during the winter, while those who got the flu in the vitamin D group had symptoms that were independent of the season.

An experiment evaluated the effects of vitamin D supplementation on influenza risk in Japanese school children. The researchers gave children either 1,200 IU vitamin D per day for three months during the winter or a dummy pill. They found that:[31]

• More children in the dummy pill group got influenza A than children in the vitamin D group.
• There was a preventive effect of 1,200 IU vitamin D per day on children getting influenza A.

The researchers concluded that taking 1,200 IU of vitamin D can help protect children against seasonal influenza A. In this study, vitamin D had no effect on influenza B, possibly because vitamin D may respond in different ways to the inflammatory proteins in the viruses.

A study conducted in 2011 looked at vitamin D levels and respiratory infections, like influenza, in a large group of British adults. The researchers found that:[32]

• For each 4 ng/ml increase in vitamin D levels in the body, there was a 7% lower chance of developing influenza.
• There was a seasonal pattern of influenza, which was the same as the seasonal pattern of vitamin D levels.
• Influenza infections decreased when vitamin D levels increased. However, since this study was observational, the researchers couldn’t conclude for certain if higher vitamin D levels protected against the flu.

Key points from research

• People who get influenza are more likely to have low levels of vitamin D.
• Vitamin D can help reduce inflammation caused by the influenza virus and increase the number of antimicrobial proteins that fight against viruses.
• Influenza infections increase during the winter, when vitamin D levels are known to decrease in the population.
• At least a dozen studies have shown that taking vitamin D supplements can reduce the chances of getting influenza.
• Having elevated levels of vitamin D may help decrease the time it takes to recover from an influenza infection.
• More and more doctors are recommending taking vitamin D to protect against influenza.

What does this mean for me?

The Vitamin D Council recommends adults take 5,000 to 10,000 IU/day, depending on body weight. Children should take about 100 IU/kg/day. Since there is a wide variation in human response to any vitamin D dose, it is important to have your vitamin D blood levels checked, after you have taken vitamin D for a few months, to make sure it is > 40 ng/ml. The Vitamin D Council offers a convenient in-home vitamin D test kit or your doctor can order the test. If get influenza, you can safely take 50,000 IU/day for 10 days to help fight off the infection, but there are no clinical studies showing it helps.

Citation

John Cannell, MD. Health condition: Influenza. The Vitamin D Council Blog & Newsletter, May 29, 2018.

References

[1] Bergman P., Lindh, AU., Bjorkhem-Bergman, L. & Lindh, JD. Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS One, 2013.

[2] Martineau, AR. et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ¸2017.

[3] Zhou, J. et al. Preventive Effects of Vitamin D on Seasonal Influenza A in Infants: A Multicenter, Randomized, Open, Controlled Clinical Trial. Pediatr Infect Dis J, 2018.

[4] Grant, W.B. and E. Giovannucci, The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918-1919 influenza pandemic in the United States. Dermatoendocrinol, 2009. 1(4): p. 215-9.

[5] The Centers for Disease Control and Prevention. Seasonal Influenza: Flu Basics, 2015.

[6] Grant WB, Giovannucci E. The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918-1919 influenza pandemic in the United States. Dermatoendocrinol, 2009. 1(4): p. 215-9.

[7] Rees, J.R., Hendricks, K., Barry, E.L.,  et al., Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trial. Clin Infect Dis, 2013. 57(10): p. 1384-92.

[8] Molinari, N.A., Ortega-Sanchez, I.R., Messonnier, M.L.,  et al., The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine, 2007. 25(27): p. 5086-96.

[9] Shrestha, S.S., Swerdlow, D.L., Borse, R.H.,et al., Estimating the burden of 2009 pandemic influenza A (H1N1) in the United States (April 2009-April 2010). Clin Infect Dis, 2011. 52 Suppl 1: p. S75-82.

[10] Ortiz, J.R., Neuzil, K.M., Shay, D.K., et al., The burden of influenza-associated critical illness hospitalizations. Crit Care Med, 2014. 42(11): p. 2325-32.

[11] The Centers for Disease Control and Prevention. Seasonal Influenza: Flu Basics, 2015.

[12] The Centers for Disease Control and Prevention. Seasonal Influenza: Flu Basics, 2015.

[13] Mayo Clinic. Diseases and Conditions: Influenza (flu), 2015.

[14] Shaman, J., Jeon, C.Y., Giovannucci, E., Lipsitch, M., Shortcomings of vitamin D-based model simulations of seasonal influenza. PLoS One, 2011. 6(6): p. e20743.

[15] Mayo Clinic. Diseases and Conditions: Influenza (flu), 2015.

[16] Laaksi, I., Ruohola, J.P., Tuohimaa, P., et al., An association of serum vitamin D concentrations < 40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr, 2007. 86(3): p. 714-7.

[17] Lang, P.O. and D. Samaras, Aging adults and seasonal influenza: does the vitamin d status (h)arm the body? J Aging Res, 2012. 2012: p. 806198.

[18] Cannell, J.J., Vieth, R., Umhau, J.C., et al., Epidemic influenza and vitamin D. Epidemiol Infect, 2006. 134(6): p. 1129-40.

[19] Sundaram, M.E., McClure, D.L., VanWormer, J.J., et al., Influenza vaccination is not associated with detection of noninfluenza respiratory viruses in seasonal studies of influenza vaccine effectiveness. Clin Infect Dis, 2013. 57(6): p. 789-93.

[20] Grant, W.B. and E. Giovannucci, The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918-1919 influenza pandemic in the United States. Dermatoendocrinol, 2009. 1(4): p. 215-9.

[21] Cannell, J.J., Zasloff, M., Garland, C.F., et al., On the epidemiology of influenza. Virol J, 2008. 5: p. 29.

[22] Yusupov, E., Li-Ng, M., Pollack, S., et al., Vitamin d and serum cytokines in a randomized clinical trial. Int J Endocrinol, 2010. 2010.

[23] Hypponen, E. and C. Power, Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr, 2007. 85(3): p. 860-8.

[24] Cannell, J.J., Vieth, R., Umhau, J.C., et al., Epidemic influenza and vitamin D. Epidemiol Infect, 2006. 134(6): p. 1129-40.

[25] Chadha, M.K., Fakih, M., Muindi, J., et al., Effect of 25-hydroxyvitamin D status on serological response to influenza vaccine in prostate cancer patients. Prostate, 2011. 71(4): p. 368-72.

[26] Sundaram, M.E., McClure, D.L., VanWormer, J.J., et al., Influenza vaccination is not associated with detection of noninfluenza respiratory viruses in seasonal studies of influenza vaccine effectiveness. Clin Infect Dis, 2013. 57(6): p. 789-93.

[27] Sabetta, J.R., DePetrillo, P., Cipriani, R.J., et al., Serum 25-hydroxyvitamin d and the incidence of acute viral respiratory tract infections in healthy adults. PLoS One, 2010. 5(6): p. e11088.

[28] Grant, W.B. and E. Giovannucci, The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918-1919 influenza pandemic in the United States. Dermatoendocrinol, 2009. 1(4): p. 215-9.

[29] Cannell, J.J., Vieth, R., Umhau, J.C., et al., Epidemic influenza and vitamin D. Epidemiol Infect, 200 Aloia, J.F. and M. Li-Ng, Re: epidemic influenza and vitamin D. Epidemiol Infect, 2007. 135(7): p. 1095-6; author reply 1097-8.. 134(6): p. 1129-40.

[30] Sundaram, M.E., McClure, D.L., VanWormer, J.J., et al., Influenza vaccination is not associated with detection of noninfluenza respiratory viruses in seasonal studies of influenza vaccine effectiveness. Clin Infect Dis, 2013. 57(6): p. 789-93.

[31] Urashima, M., Segawa, T., Okazaki, M., et al., Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr, 2010. 91(5): p. 1255-60.

[32] Berry, D.J., Hesketh, K., Power, C., Hyppönen, E., Vitamin D status has a linear association with seasonal infections and lung function in British adults. Br J Nutr, 2011. 106(9): p. 1433-40.