Did you ever stop to wonder why we have a “cold and flu season” — why we tend to get these illnesses in the cold, dark winter? And surely you have noticed that some people are naturally resistant to colds and flu, even while others around them are coughing, hacking, and spreading the viruses like mad. As science now tells us, the answer, or at least part of it, lies in the sunshine vitamin known as vitamin D.

For years we thought of vitamin D as just another vitamin, but we now know that vitamin D is much, much more. This “vitamin” is really a hormone precursor — it is the stuff the body uses to make a potent hormone known as calcitriol, a hormone capable of signaling over 1000 genes to express or suppress themselves.

Our bodies turn the vitamin D we produce — from sunlight exposure or dietary sources — into this hormone, which not only keeps us alive by regulating blood calcium, but also directly influences the functioning of every organ system. The heart, kidneys, gut, lungs, and yes, the immune system, are all influenced by the vitamin D hormone. Your risks of fracture, heart attack, TB, depression, periodontal disease, multiple autoimmune diseases and, as it now appears, even the flu are dramatically lowered if you have optimal vitamin D blood levels. Overall mortality, in fact, is significantly reduced — by 8% — with even modest vitamin D supplementation. Activated vitamin D (calcitriol) is a complex hormone with as many mechanisms of action as the 1000 human genes it regulates.

Seasonal variation in flu and vitamin D

It’s commonly held that influenza is a highly infectious virus spread by the sick to those who are well. Many people also assume that the virus is spread more easily in the winter because that’s when everyone is “huddled together” indoors.

Decades ago, however, a noted scientist questioned these assumptions and went on to propose that there is an unidentified “seasonal stimulus” associated with flu outbreaks.

As this physician, Dr. Hope–Simpson, documented over and over again, flu incidence was tightly correlated with the winter season, and it was not consistently spread from ill to well after all.

Indeed, we all recognize that there is a flu season — the dark wintertime — but we have also witnessed that not everyone who is exposed to the virus gets sick.

It is now becoming clearer that low wintertime levels of vitamin D — the sunshine vitamin — may indeed be the “seasonal stimulus” that triggers flu outbreaks and influences individual susceptibility to influenza infection.

References

How “the antibiotic vitamin” improves immunity to the flu

Reams of data published in the past decade have documented the roles vitamin D plays in nearly all bodily systems, and the immune system is no exception. Researchers report fast-growing evidence that vitamin D exerts profound effects on the part of the immune system known as innate immunity — a recent article in Science News even tagged vitamin D as the “antibiotic vitamin.”

Innate immunity is at the heart of a defense system that is “hard-wired” to respond rapidly to microorganisms using genetically encoded response mechanisms.

One such innate immune system response involves production of broad-spectrum antimicrobial agents known as antimicrobial peptides (AMP’s). Our skin cells and cells lining our internal passageways (epithelial cells), as well as a wide range of immune cells (such as macrophages) create these natural antibiotic AMP’s upon exposure to microbes. This action, however, is dependent on the presence of vitamin D!

Another mechanism described recently in Nature Immunology reveals that vitamin D is mandatory for the proper signaling and activation of our immune system’s T-cells upon their exposure to foreign pathogens. Without it, the T-cells will not activate!

This means that our bodies produce their own “homemade” antibiotics — some 200 different types — all of which are up-regulated and stimulated by the active vitamin D hormone. These homemade antibiotics attack and irreversibly damage a wide range of fungi, bacteria, and viruses.

Vitamin D and influenza: the data

Much of the story of the vitamin D–influenza link is the compelling tale of the work of Dr. John Cannell. I have been in personal communication with Dr. Cannell over a number of years, and have carefully followed his research and that of his non-profit Vitamin D Council.

When I first spoke with Dr. Cannell several years ago, he told me about his work as a psychiatrist at the Atascadero State Hospital in California. Interested in vitamin D, and suspecting common vitamin D deficiency among his inmates, Dr. Cannell regularly tested inmates for vitamin D adequacy. As expected, he found they had abnormally low levels of vitamin D and, after explaining the benefits of this vitamin, he prescribed for the inmates 2000 IU vitamin D3 (cholecalciferol) a day.

In the late winter of 2005, a virulent strain of influenza hit the maximum-security psychiatric hospital, and although 10% of the 1200 patients ultimately developed the flu’s fever and debilitating muscle aches, there were no cases of flu among Dr. Cannell’s inmates, who had been given daily vitamin D supplements. In a 2006 interview Dr. Cannell said, “First, the ward below mine was quarantined, then the wards on my right, left, and across the hall.” And even though Cannell’s inmates had mingled with the others prior to quarantine, they still managed to avoid the flu.

How was it that his inmates were able to dodge the flu? A few months later, he came across a scientific report stating that vitamin D was found to increase the production of natural antimicrobial compounds in white blood cells. It was then that Dr. Cannell’s Aha! moment occurred. Could it have been the vitamin D he routinely gave his inmates that protected them from the flu? Encouraged by his colleagues, Dr. Cannell and seven other noted vitamin D scholars reviewed more than 100 articles that — in one way or another — linked vitamin D with enhanced immunity and fewer respiratory infections.

The research reports that pointed to a D–influenza link included findings like these:

  • Many studies noted an association between rickets, the classic childhood disease of vitamin D deficiency, and increased respiratory infections.
  • A research comparison of 80 rickets-free children found that children with very low 25(OH)D levels (less than 10 ng/mL) were 11 times more likely to be infected with respiratory infections than children with higher vitamin D levels.
  • A 1994 study showed that intervention with vitamin D (60,000 IU/week) and calcium (650 mg/day) produced a significant reduction in the incidence of infections in children with subclinical rickets.

These early research findings, along with his own experience with his inmates, led Dr. Cannell to boldly suggest that vitamin D deficiency could underlie a vulnerability to influenza infection. Since the first article on influenza and vitamin D was published in 2006, a new body of research has developed that strongly supports the hypothesis that low vitamin D levels increase vulnerability to flu and that high vitamin D levels offer a protective effect.

In 2007, Dr. Cannell and colleagues published a second paper on the vitamin D–influenza connection in Virology Journal. Here they explored nine intriguing questions, including: “Why is influenza both seasonal and ubiquitous, and what happens to the virus between epidemics?”... “Why are influenza epidemics so explosive?”... “Why do they end so abruptly?” and so forth. A unifying element in answers to each of these questions pertains to the fascinating role vitamin D plays in enhancing innate immunity.

A series of new studies lends growing support to the theory that low vitamin D levels increase our vulnerability to influenza.

  • A study of young Finnish men in military service reported that those with vitamin D deficiency had significantly more absence from duty due to respiratory infection than the servicemen who were not vitamin D-deficient.
  • A Turkish study of newborn infants found that those with acute lower respiratory infection had lower levels of vitamin D (along with their mothers) than other newborns who were free of respiratory infection.
  • In a study of African-American women, self-reported symptoms of colds and influenza were more than three times lower in the group given 800 IU supplemental vitamin D3 daily over two years than the women in the placebo group. Plus, this relatively low dose effectively abolished the seasonality of colds and flu. Furthermore, a higher dose of 2000 IU given daily during the last year of this three-year trial virtually eradicated all reports of colds and flu.
  • A recent report in the Journal of Pediatric Research summarizes scientific consensus to the effect that infants and children, in the face of vitamin D deficiency, appear more susceptible to viral infections than bacterial ones. They concluded that the newly recognized connections between vitamin D, infections, and immune function suggest a role for vitamin D supplementation in the pediatric population.
  • In 2010, further support for the idea was offered in a small, but perhaps the first rigorously designed clinical trial evaluating the relationship between vitamin D and physician-diagnosed seasonal influenza. Japanese researchers showed that vitamin D supplements of 1200 IU per day significantly cut the incidence of seasonal influenza among the several hundred schoolchildren they followed — even though they didn’t even start supplementing until December — well into the flu season! (Asthma attacks in the subset of children with a previous diagnosis of asthma were also dramatically reduced.)

Even more interesting than scientific study — real-life swine flu prevention with vitamin D

While the scientific studies connecting low vitamin D and influenza are interesting, what I find even more telling are informal reports from clinical settings, where the use of vitamin D amongst patients was tightly linked to a reduction in their vulnerability to emergent swine flu variants (H1N1). Two very interesting reports from clinical settings were submitted to Dr. Cannell and published in his Vitamin D Council Newsletter in September 2009. These reports help me see the real day-to-day value of vitamin D supplementation even more clearly than the scientific studies do.

The first report is from a doctor in Wisconsin, Dr. Norris Glick, who wrote to Dr. Cannell:

Your recent newsletters and video about Swine flu (H1N1) prompted me to convey our recent experience with an H1N1 outbreak at Central Wisconsin Center (CWC). Unfortunately, the state epidemiologist was not interested in studying it further, so I pass it on to you since I think it is noteworthy.

CWC is a long-term care facility for people with developmental disabilities, home for approx. 275 people with approx. 800 staff. Serum 25-OHD has been monitored in virtually all residents for several years and patients supplemented with vitamin D.

In June 2009, at the time of the well-publicized Wisconsin spike in H1N1 cases, two residents developed influenza-like illness (ILI) and had positive tests for H1N1: one was a long-term resident; the other, a child, was transferred to us with what was later proven to be H1N1.

On the other hand, 60 staff members developed ILI or were documented to have H1N1: of 17 tested for ILI, eight were positive. An additional 43 staff members called in sick with ILI. (Approx. 11–12 staff developed ILI after working on the unit where the child was given care, several of whom had positive H1N1 tests.)

So, it is rather remarkable that only two residents of 275 developed ILI, one of which did not develop it here, while 103 of 800 staff members had ILI. It appears that the spread of H1N1 was not from staff-to-resident but from resident-to-staff (most obvious in the imported case) and between staff, implying that staff were susceptible and our residents protected.

Sincerely,
Norris Glick, MD
Central Wisconsin Center
Madison, WI

Dr.Cannell’s Comment:

This is the first hard data that I am aware of concerning H1N1 and vitamin D. It appears vitamin D is incredibly protective against H1N1. Dr. Carlos Carmago at Mass General ran the numbers in an email to me. Even if one excludes 43 staff members who called in sick with influenza, 0.73% of residents were affected, as compared to 7.5% of staff. This 10-fold difference was statistically significant (P<0.001). That is, the chance that this was a chance occurrence is one less than one in a thousand.

Second, if you read my last newsletter, you will see that children with neurological impairments, like the patients at your hospital, have accounted for 2/3 of the childhood deaths for H1N1 so far in the USA. That is, the CDC knows, because they reported it, that patients with neurological impairments are more likely to die from H1N1.

The second report is from a doctor in Georgia, Dr. Ellie Campbell, who wrote to Dr. Cannell:

Thanks for your update about the hospital in Wisconsin. I have had similar anecdotal evidence from my medical practice here in Georgia. We are one of the 5 states with widespread H1N1 outbreaks.

I share an office with another family physician. I aggressively measure and replete vitamin D. He does not. He is seeing one to 10 cases per week of influenza-like illness.

In my practice — I have had zero cases. My patients are universally on 2000–5000 IU to maintain serum levels 50–80 ng/mL.

Ellie Campbell, DO
Campbell Family Medicine
3925 Johns Creek Court
Ste A Suwannee GA 30024

I’m confident that as time goes by, more and more researchers and healthcare providers will be reporting their data and experiences with vitamin D supplementation and flu. You may enjoy following the work of John Cannell by subscribing to the Vitamin D Council Newsletter, or listening to Dr. Cannell discuss vitamin D and the flu on YouTube.

So what’s a person to do?

So far, the US Centers for Disease Control (CDC) has not responded to requests from Dr. Cannell and colleagues that the US take a serious look at the link between low vitamin D and flu susceptibility. The Public Health Agency of Canada, in contrast, is investigating the role vitamin D might play in protection against the constantly-morphing influenza A/H1N1 variants. But this research by the Canadian government, while moving in the right direction, will likely take years.

Meanwhile, a study published in 2010 by Dr. Cannell reports that of a random sample of over 3000 postmenopausal American women, nearly 60% were vitamin D-deficient! And realistically, we can expect the cold and flu season to happen upon us with new variants of these viruses with each new year. Given the safety of vitamin D and its likely benefits, it’s reasonable to hedge your bets and take sufficient vitamin D to reach the suggested protective vitamin D blood level of 50 to 80 ng/mL 25(OH)D. This represents a vitamin D blood concentration consistent with what’s obtainable from abundant natural summertime sunlight exposure. Keep in mind that the amount of vitamin D needed to reach this ideal blood level can vary widely between individuals, depending on sunlight exposure, vitamin D reserves, skin color, body fat, age, and the like.

As Dr. Cannell reports, most people will probably require somewhere between 2000 IU and 5000 IU vitamin D a day to reach the 50–80 ng/mL level. Luckily, with vitamin D we know the blood level we are striving for (50–80 ng/mL), so you can safely take 2000 units a day for eight weeks, then ask your physician to test your 25(OH)D blood level. (See our article on vitamin D testing and treatment.) Generally, each additional 1000 IU of vitamin D supplemented will raise your blood levels about 10 ng/mL.

Wave goodbye to seasonal colds and flu

You don’t have to wait until you feel the symptoms of a cold or the flu coming on — you can begin today and build better immunity against colds and flu infections by supplementing with vitamin D.

References

1 Zittermann, A., et al. 2009. Vitamin D deficiency and mortality. Curr. Opin. Clin. Nutr. Metab. Care, 12 (6), 634-639. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/19710612 (accessed 10.28.2009).

  Autier, P., & Gandini, S. 2007. Vitamin D supplementation and total mortality: A meta-analysis of randomized controlled trials. Arch. Intern. Med., 167 (16), 1730-1737. URL: http://archinte.ama-assn.org/cgi/content/full/167/16/1730 (accessed 10.28.2009).

  Giovannucci, E. 2007. Can vitamin D reduce total mortality? Arch. Intern. Med., 167 (16), 1709-1710. URL (no abstract available): http://www.ncbi.nlm.nih.gov/pubmed/17846388 (accessed 10.28.2009).

2 Cannell, J., et al. 2008. On the epidemiology of influenza. Virol. J., 5, 29. URL: http://www.virologyj.com/content/5/1/29 (accessed 10.28.2009).

3 Raloff, J. 2006. The antibiotic vitamin. Science News, 17 (20), 312-317. URL: http://www.sciencenews.org/articles/20061111/bob9.asp (accessed 10.29.2009).

4 Cannell, J., et al. 2008.

  Gombart, A., et al. 2005. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB, 19 (9), 1067–1077. URL: http://www.fasebj.org/cgi/content/full/19/9/1067 (accessed 10.28.2009).

5 von Essen, M., et al. 2010. Vitamin D controls T cell antigen receptor signalling and activation of human T cells. Nat. Immun. [Epub ahead of print.] URL: http://www.ncbi.nlm.nih.gov/pubmed/20208539 (accessed 03.12.2010).

6 Cannell, J., et al. 2008.

  Gombart, A., et al. 2005.

7 Gombart, A., et al. 2005.

8 Cannell, J., et al. 2006. Epidemic influenza and vitamin D. Epidemiol. Infect., 134 (6), 1129-1140. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/16959053 (accessed 10.28.2009).

9 Wayse, V., et al. 2004. Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y. Eur. J. Clin. Nutr., 58 (4), 563-567. URL: http://www.nature.com/ejcn/journal/v58/n4/full/1601845a.html (accessed 10.28.2009).

10 Rehman, P. 1994. Sub-clinical rickets and recurrent infection. J. Trop. Pediatr., 40 (1), 58. URL (no abstract available): http://www.ncbi.nlm.nih.gov/pubmed/8182788 (accessed 10.28.2009).

11 Adams, J., & Hewison, M. 2008. Unexpected actions of vitamin D: New perspectives on the regulation of innate and adaptive immunity. Nat. Clin. Pract. Endocrinol. Metab., 4 (2), 80-90. URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2678245/?tool=pubmed (accessed 10.29.2009).

12 Cannell, J., et al. 2008.

13 Laaksi, I., et al. 2007. An association of serum vitamin D concentrations <40 nmol/L with acute respiratory tract infection in young Finnish men. Am. J. Clin. Nutr., 86 (3), 714-717. URL: http://www.ajcn.org/cgi/content/full/86/3/714 (accessed 10.29.2009).

14 Karatekin, G., et al. 2009. Association of subclinical vitamin D deficiency in newborns with acute lower respiratory infection and their mothers. Eur. J. Clin. Nutr., 63 (4), 473-477. URL: (abstract): http://www.ncbi.nlm.nih.gov/pubmed/18030309 (accessed 10.29.2009).

15 Alioa, J, and Li-Ng, M. 2007. Re: Epidemic influenza and vitamin D. Epidemiol Infect., 135 (7), 1095-1096. URL: http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=1344952 (accessed 10.29.2009).

See also:

  Chart showing incidence of reported cold/influenza symptoms according to season: http://www.virologyj.com/content/5/1/29/figure/F2

16 Walker, V. & Modlin, R. 2009. The vitamin D connection to pediatric infections and immune function. Pediatr. Res. [Epub ahead of print.] URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/19190532 (accessed 10.29.2009).

17 Urashima, M., et al. 2010. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am. J. Clin. Nutr. (Epub ahead of print.) URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/20219962 (accessed 03.16.2010).

18 Heller, L. 2009. Canada examines vitamin D for swine flu protection. URL: http://www.nutraingredients-usa.com/Research/Canada-examines-vitamin-D-for-swine-flu-protection (accessed 10.29.2009).

19 Millen, A., et al. 2010. Predictors of serum 25-hydroxyvitamin D concentrations among postmenopausal women: The Women’s Health Initiative Calcium Plus Vitamin D Clinical Trial. Am. J. Clin. Nutr. (Epub ahead of press). URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/20219959 (accessed 03.16.2010).

References on seasonal stimulus (seasonal varition) in flu epidemics and vitamin D

Hope-Simpson, R.1992. The Transmission of Epidemic Influenza. NY: Plenum Press. http://www.virologyj.com/sfx_links.asp?ui=1743-422X-5-29&bibl=B2

Hope-Simpson, R., & Golubev, D. 1987. A new concept of the epidemic process of influenza A virus. Epidemiol. Infect., 99, 5-54. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/3301379 (accessed 10.29.2009).

Hope-Simpson, R. 1986. The method of transmission of epidemic influenza: Further evidence from archival mortality data. J. Hyg. (London), 96 (2), 353-375. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/3517157 (accessed 10.29.2009).

Hope-Simpson, R. 1984. Age and secular distributions of virus-proven influenza patients in successive epidemics 1961–1976 in Cirencester: Epidemiological significance discussed. J. Hyg. (London), 92 (3), 303-336. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/6736641 (accessed 10.29.2009).