Is Vitamin D the "Missing Link" of Flu Prevention?

Vitamin D and Flu Prevention: Part 1

Influenza (the flu) is the poster-child of seasonal variability in an infectious disease. During "flu season" rates of influenza skyrocket, but in the warm, summer months the virus is seemingly dormant. I think that last bit does a particularly good job of beginning to elude to the commonly held beliefs surrounding the flu. Public officials tell us every year that this is going to be a bad year for the flu- perhaps the worst one yet. I think that most people conjure up an image of a virus that "attacks" every year, is defeated (fails to infect everyone), goes into hiding for the summer and makes itself bigger and better, and mounts an attack again the following year. It seems simple enough why people get sick- if you come into contact with enough germy people and if the virus is "bad" enough the virus will get you; it's only a matter of time. But what if the virus isn't the biggest variable in this equation- what if it's us?

There is a number of theories for what makes us more susceptible to infection in the winter. The start and end of the school year, the fall of absolute humidity in the winter months which dries out mucous membranes, seasonal patterns of behavior, temperature fluctuations, changes in viral transferability, and changes in host (human) immune function throughout the year all almost certainly play some role in influenza transmission [2]. Out of all of those reasons, however, one theory has risen above the rest in terms of answering unanswered questions (below) and promising research trials (to be discussed in Part 2).

Host (human) immune function is dependent on Vitamin D

Vitamin D is considered to be a hormone- a chemical that is made in one cell or gland (skin cells), released into the blood stream, and affects other cells in the body. Vitamin D is known to regulate at least 913 genes [3], including many that regulate immune function. Vitamin D is the major regulator of several antimicrobial peptides (AMPs) (you're body's in-house, broad spectrum antibiotics), namely cathelicidin and beta-defensin [3,4]. Among other functions, AMPs are known to protect the body's barrier surfaces (lungs, mouth and throat, gut) by creating a hostile antimicrobial shield [5]. This alone has tremendous implications in disease transferability! If the virus can not get past these barriers and get into the body it makes it tremendously difficult for it to make you sick. Vitamin D is also a key player in the innate immune system [3,5], which is the body's first, non-specific line of defense against pathogens. One way it does this is by enhancing TH3 cell function- T Helper cells that keep the rest of the immune system running smoothly. Fascinatingly, new research has shown that cells of the immune system and epithelium (barriers) are able to convert the non-active form of vitamin D into it's active metabolite [6]. This mechanism may further demonstrate the immune system's dependance on this modest little hormone.

Vitamin D as the "seasonal stimulus" answers many otherwise unanswerable questions about Influenza's odd behavior [5]

1. Why is Influenza both seasonal and ubiquitous (everywhere) and where is the virus between epidemics?
It is unlikely that the virus hides each summer and magically comes out in the winter. What's more likely is that the virus is around us (and in us) all year-round, but during times of enhanced immunity (sun exposure) we are able to fight it and remain asymptomatic.

2. Why are the epidemics so explosive?
As vitamin D levels begin to drop in the fall and winter months, so does our ability to fight infections. After a prolonged amount of time without sun exposure people's vitamin D levels will begin to fall, resulting in more and more people becoming increasingly more prone to infection. Once people's vitamin D levels drop below their tolerable threshold (which is most likely different from person to person), a subset of the population would find themselves suddenly susceptible to infection.

3. Why do epidemics end so abruptly?
It is likely that there is a sub-population of "good transmitters" within each population, which may be associated with each person's degree of Vitamin D deficiency. The depletion of this limited supply of good hosts most likely plays a large role in flu season's speedy resolution.

4. What explains the frequent coincidental timing of epidemics in countries with similar latitudes [5]? Why is the seasonal pattern of Influenza so weak or non-existent in equatorial regions [1]?
The peak of the last 25 epidemics in France and the USA occurred within a mean of four days of each other [5]. Similar latitudes likely follow a similar pattern (in both severity and seasonality) of impairments in innate immunity. This would also explain why regions closest to the equator experience fewer cases of influenza and seem to exhibit no pattern of seasonality [1].

5. Why is the serial interval so obscure?
The "serial interval" refers to the amount of time it takes for an infected person to make a well person sick. The serial interval has been shown for a number of other respiratory diseases, but has yet to be established for Influenza [5]. It appears that the presence of "good transmitters" among a population, who's infectious period is limited, makes this incredibly hard to measure for Influenza. The variation in Vitamin D status from one individual to another is likely one of many factors that seperates the "good transmitters" from the poor transmitters.

6. Why is the secondary attack rate so low?
For a  (supposedly) "highly contagious" virus such as Influenza, it's secondary attack rate is surprisingly low- about 15-20% at most, compared to 70% for measles and 58% for rhinovirus [5]. This is inconsistent with the idea that the virus sustains itself via regular sick-to-well transmission. The presence of a limited number of "good transmitters" as a result of vitamin D variation likely plays a role. Surely we've all known a person who always gets sick when there's a bug going around? It would be interesting to measure that person's vitamin D levels!

7. Why did epidemics in previous ages spread so rapidly, despite the lack of modern transportation?
"If Influenza were embedded in the population, only to erupt when impairments in innate immunity create a susceptible subpopulation, the disease would only give the appearance of spreading. Instead, it would appear in large segments of the population seasonally, and almost simultaneously, as long as good transmitters were available" [5].

8. Why are so few sickened by direct aerosol inoculation of influenza virus?
If the virus is highly infectious, one would expect most, if not all, people to fall ill when exposed to the virus. However, this is not the case. Even if the virus is sprayed directly into patient's eyes, nose and throat (I swear they really did this in 1918 and 1919) none of the volunteers became ill in any way. Other studies found similar results, where none or relatively few of the volunteers became sick after direct exposure to the virus. Once again, we must ask ourselves what makes one person susceptible and one person all but impervious to infection?

9. Why have influenza-related mortality and hospitalization rates significantly increased in the last three decades, despite profound increases in the rate of influenza vaccination?
Simply said, because vaccine manufacturers and researchers grossly overestimate the effectiveness of the flu vaccine every year. The flu vaccine lowers the incidence of the flu by 1.55%. If you want to know why I am so certain in saying so, please check out my previous blog posts on the flu vaccine here.


Check back soon for Part 2 of this series- I will be going over the current research on vitamin D as a means of preventing the flu.


Stay healthy out there, folks!



References:
[1] Juzeniene, Asta et al "The seasonality of pandemic and non-pandemic influenzas: the role of solar radiation and vitamin D" 2010 [PMID 21036090]
[2] Shaman, Jeffrey et al "Shortcomings of vitamin D-based model simulations of seasonal influenza" 2011 [PMID 3108988]
[3] Lang, PO "How important is vitamin D in preventing infections?" 2012 [PMID 23160915]
[4] Aranow, Cynthia et al "Vitamin D and the immune system" 2011 [PMID 3166406]
[5] Cannell, John et al "On the epidemiology of influenza" 2008 [PMID 2279112]
[6] Sundaram, Maria et al "Vitamin D and influenza" 2012 [PMID 3649720]