Can Vitamin D Keep Me From Getting Sick?

Flu season is here, and while many of us think the only thing that we can do to keep from catching the flu is getting that notorious flu shot (John's Hopkins' Scientist Slams Flu Vaccine), avoiding the crowds in the malls, and using massive amounts of hand sanitizer to disinfect ourselves, it turns out there is a much simpler thing we can do- ensure that our powerful and highly versatile immune system has one of the most important raw materials it needs to do its job in protecting us: Vitamin D.

Basics of the Immune System

There are two basic components to our body's immune response: the innate immune response and the adaptive immune response. The innate immune response is the more primitive of the two but also extremely powerful; the innate immune system has the same response to all microbes (bacteria and viruses) it encounters, with no memory of previous encounters to help dictate the best way to eliminate the newly detected microbe. The adaptive immune response on the other hand keeps track of previous encounters with microbes and what specific mechanisms were needed to eventually eliminate it- this is the basis of developing immunity.

While the adaptive immune response is much more complex and sophisticated and typically found in more evolved species, it can easily be tricked by equally sophisticated bacteria and viruses which mutate to avoid being detected as a familiar foe that the adaptive immune system has tackled in the past.  Have you ever wondered why they need to come up with a new flu shot every year? It is because the flu viruses is constantly mutating, and the vaccine makers need to guess at what this years popular strains may be. Even when we catch a cold or flu and eventually mount a full immune response, the memory of that specific response does not aid us when a newly mutated cold or flu virus comes along.

However, even if these microbes mutate, there are certain structures that are shared by various classes of microbes that are not present on normal host cells in the human body, and this is what is used by the innate immune system to detect and mount an attack on them.  This is what makes the innate immune response such a powerful tool in fighting off previously unencountered infections. For example, phagocytes express receptors for lipopolysaccharide (LPS) which are present in the cell walls of many bacterial species but not produced by human cells. There are many other components to innate immunity to respond to many different bacteria, viruses, and fungi but a full description is beyond the scope of this blog and can be found in basic texts on immunology. The main point is that the components of innate immunity have evolved to recognize structures of microbes that are often essential for the survival and infectivity of these microbes. By supporting the innate immune response, your chances of fighting off the next cold or flu quickly near the point of entry (within the lymphatic system) before it infects the rest of the body are significantly improved! Unfortunately, there are some pathogenic microbes have evolved to resist the mechanisms of innate immunity and are therefore able to colonize host cells, some examples are pneumococci, staphylococci, and streptococci.

The Role of Vitamin D in Innate Immune Function

A very good overview of the role of Vitamin D in the innate immune function response is given in the following article from the Journal of Infection and Immunity:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519414/

Essentially, when cells of the innate immune system such as macrophages encounter a microbe, toll like  receptors (TLR) on the macrophage trigger the production of an enzyme in the macrophage called CYP27B1, which is a member of the cytochrome P450 family. This enzyme, found in the immune cell's mitochondria, triggers conversion of the inactive or stored form of vitamin D called 25 hydroxy vitamin D3 (25-OH vitamin D3) into its active form 1,25 dihydroxy vitamin D3 (1,25-(OH)2 Vitamin D3) which in turn activates the vitamin D receptor (VDR) within the immune cell which is responsible for transcription of genes to produce antimicrobial peptides (AMPs) to attack and attempt to kill the microbe. Note something very important that will be discussed in a future blog post: the inactive 25-OH Vitamin D3 needs to be hydroxylated to its active form 1,25-(OH)2 Vitamin D3 in order to "switch on" the antimicrobial activities of the immune cell, and this hydroxylation takes place in the cells mitochondria. If there was something that interfered with this mitochondrial function or the mitochondria in general, this conversion to active vitamin D would be impaired as would the resulting immune response.

The detection of the microbe by the macrophage also sets of a chain reaction of cytokine production (messengers) to attract a larger number of immune cells, such as natural killer (NK) cells which are attracted by the cytokine IL-12, to the site of infection to help kill the microbe before it is able to invade the rest of the cells in the body and cause more damage, and also trigger inflammation at the site of infection to help "wall off" the area to prevent spread of the infection. The NK cells secrete a cytokine called interferon gamma which in turns is detected by the macrophage and stimulates the production nitric oxide inside the macrophage as a more potent mechanism to kill the invading microbe. It turns out that the synthesis of nitric oxide depends on having sufficient levels of the active form of vitamin D (1,25-(OH)2 Vitamin D) present already (see the following article published in the Immune Network Journal: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816953/).

Have you noticed that the first sign that you are sick is often a lump in your throat? This is inflammation of the tonsils in the lymphatic system, meaning your innate immune system has detected a microbial invader and is trying to contain it at the point of entry and activate your body's immune response. Sometimes the soar throat resolves itself and often a cold or flu doesn't appear to manifest, this is what happens when the innate immune response combined with the adaptive immune response as necessary was adequate at containing the microbial invader  and eliminating it before the rest of the body's cells were impacted.

So we see that having a sufficient level of stored vitamin D  (25 hydroxy vitamin D3) is crucial for activation of the antimicrobial response by the innate immune system. 25 hydroxy vitamin D3 is what we typically get in our blood test when we request our vitamin D level to be tested. The reference range for proper vitamin D levels is 25 - 80 ng/ml. Emerging science is suggesting that targeting the upper part of this range (greater than 50 ng/ml) is needed for optimum health; it has to be high enough to meet the instantaneous needs of the immune system to combat microbial infections that are detected.

How Do We Get Sufficient Vitamin D?

Normally humans are supposed to get their vitamin D levels met from exposure to the sun. Ultraviolent  (UV) radiation from the sun, UVB in particular, reacts with a cholesterol precursor in our skin called 7-dehydrocholesterol to form vitamin D3 (referred to as cholecalciferol), which is then hydroxylated (primarily in the liver) to form 25-hydroxy vitamin D3 which is the body's stored form of vitamin D. Again a note here that will be discussed in future blog posts: this hydroxylation of cholecalciferol to 25-OH D3 takes place in the mitochondria of the cell through the cytochrome P450 enzyme reaction; if the cell mitochondria is impaired for some reason, this conversion will not take place and a state of vitamin D deficiency could exist even with adequate sun exposure or vitamin D3 supplementation.

Note that vitamin D is what is known as fat soluble, being it is stored in fat and hence conserved by the body, as opposed to being water soluble which means the concentration is tightly controlled and any excess is flushed out by the body. The reason this is important is two-fold: first, the body does not need to be exposed to the sun every single day or multiple times throughout the day in order to maintain the proper 25-OH vitamin D3 levels because it can be stored (can last up to a month apparently); second, supplementation with vitamin D3 needs to be done with care to ensure levels do not build up to what would be considered toxic. The toxic level of 25-D is still under debate, some seem to think it is anything above 80 ng/ml while others argue it is 100 or 125 ng/ml while still others argue there is no toxic level!

When we get our vitamin D from the sun we do not need to worry about toxicity, as the body naturally contains feedback loops to activate and deactivate enzymes to ensure excessive vitamin D is not created (you can't be nature!). When roughly 40% of our skin is exposed to sunlight without sunscreen and when the UV index is above 3 (between 10am - 4pm during the summer months in North America), the body can create as much as 10,000 IUs of vitamin D in as little as 20-30 minutes, depending on the pigmentation of your skin. This is often sufficient to maintain proper blood levels of 25-OH vitamin D3 if you are exposed to the sun in such a way 3 or 4 times per week for 20-30 minutes without sunscreen.
An image borrowed from the following website: Vitamin D Wiki:

The problem is in the winter months in North America, where most of the United States for example is not at a low enough latitude for the UV index to be above 3 except for perhaps a relatively brief amount of time around noon in the more pleasant weather areas of the country, and more over most people are indoors or heavily bundled up with clothing due to the cold weather. You can check what the hourly UV index where you live here: http://www.uvawareness.com

Now this starts to make you realize why there is such a thing as the "flu season" in the United States. Clearly flu viruses don't just come into existence in October and naturally die off in March. It is the fact the most people become heavily deficient in vitamin D due to the weather, which makes it easy for the flu virus to make it past the weakened innate immune system and for people to become sick. and this makes it easier for the virus to spread.

For those of us who choose to live in areas where it is impossible to maintain adequate 25-OH D3 levels from the sun alone, it is crucial that we supplement with an appropriate amount of vitamin D3. Blood testing is important to make sure you are taking the correct amount. While many foods are fortified with vitamin D, this is often inadequate to get vitamin D levels into preferred part of the range in the winter months. The amount some people need to take to get to a 50-80 ng/ml 25-OH vitamin D level can at first seem a bit surprising, with dosages of 10,000 IU per day for an adult. But when you consider what the body itself was able to create from the sun during the summertime, this amount should not be very surprising. A few charts inserted below showing what level of supplementation is required to target a specific 25-OH vitamin D blood level, from  Vitamin D Wiki. The amount each person needs to take is quite individual, depending on skin pigmentation, latitude in which you live, lifestyle habits in terms of length of sun exposure and time of day, and any underlying chronic issues which may be utilizing the body's supply of vitamin D at a high rate.

Looking Forward

I hope this post explained some of the details I have felt are lacking elsewhere when it comes to explaining the connections between vitamin D supplementation and how it supports the functioning of our immune system. I discussed here the benefits of vitamin D in combating microbial infections such as the flu. Now consider the possibility for a moment that many of the chronic diseases we are faced with, such as diabetes, cancer, asthma, allergies, autism, etc. all have their roots in microbial infection. Further, the microbial infection alters cell metabolism in such a way that it becomes difficult to the body to detoxify toxins such as pollutants and heavy metals found in our environment and in the foods we consume and products we use, and the accumulation of these toxins leads to excess free radical production (oxidative stress) which causes tissue damage which in turn triggers an inflammatory response to activate the immune system to effect tissue repair. An immune system that is busy with extensive tissue repair leaves the body more susceptible to existing and new microbial infections.

We can see how very quickly a "chicken-or-the-egg" question comes up given the circular connections, but in the end what we have is a body trapped in a state of chronic oxidative stress, chronic inflammation, chronic infection, and chronic toxicity. The result of these factors is what I believe is the source of many chronic diseases. While antioxidant supplements can help address the free radials underlying oxidative stress, and while some supplements and medications can be used to treat chronic inflammatory conditions, these approaches are often just treating the symptoms and not the underlying cause of the chronic condition. 

In future posts in this blog, I will be exploring how many chronic diseases that exist have their causative roots in chronic microbial infection coupled with chronic toxicity (heavy metal toxicity is the worst offender), and how solutions to chronic disease can come by addressing these underlying causes, rather than the current allopathic medical approach of treating symptoms.