Vitamin D is a well known nutrient, however, I think few
people really understand the significance of this important vitamin. To begin with, vitamin D should hardly be classified as a
vitamin at all, since it is really hormone that helps to signal our bodies
calcium status (1). However vitamin D (VD) has been
implicated in a range of processes including obesity, renal disease,
cardiovascular disease, male fertility and even sex hormone production (2,3). With all these different actions of VD
it is tough to know where to start, as there is so much research on how VD
affects so much of our lives. I do
think these many actions are very interesting, and well deserving of a post in
their own right, but I would like to focus this post on VD’s interactions with
the immune system, as that is a topic consistently on my mind these days. To do that we will first go over a
quick look at VD metabolism, and then get into its effects on immunity, and
finish up with some thoughts about our own VD status.
Vitamin
D Metabolism
As humans there are two main ways we can get VD: through sun
exposure and supplementation. We
will go over the optimal VD levels at the end of the post, but first lets see
how sunlight affects our VD status.
As we have seen before cholesterol is a very important
molecule for all mammals, and part of this is because it is the most basic
precursor to VD. Cholesterol in
the skin is converted directly to 7-dehydrocholesterol. This is the molecule that will absorb
energy from UV B rays and turn into cholecalciferol. Some of you may recognize cholecalciferol, as it is the form
of VD that is used in most D3 supplements. Cholecalciferol is then transported to the liver, where it
is further converted to calcidiol, or 25(OH)D. This calcidiol is then transported one more time, this time
to the kidneys, where, with the help of parathyroid hormone, it is converted to
calcitrol (1,25(OH)2D), which is the “active form” of VD that is
what is actually important. This 1,25(OH)2D
is what will then travel through your body and can activate the VD receptor
(VDR) that will activate the various processes VD is known to contribute to.
For those of you who might have gotten a little lost in all
of that, here is a nice figure that shows VD metabolism in a visual form that
is definitely helpful to understand all of this.
(3)
Vitamin
D and Immunity
VD is known to interact with both the both innate and
adaptive immune systems. The
innate immune system is the defenses that all mammals are born with, and have
been programmed through thousands of years of evolution. On the other hand, the adaptive immune
system is the part that allows us to build defense to things we encounter
during our life. As an example, a
flu shot is built around our adaptive immune system. We force our selves to contact a pathogen so that we build
up a defense to it. However,
something like inflammation is an example of innate immunity, this is a process
that most animals have that allows them to properly fight off a variety of
pathogens and other injuries.
A group of important mediators for the innate immune system
is the toll-like receptors (TLR’s), specifically TLR4. Many of you may have heard of this
specific receptor, as it is integral in our response to lipopolysaccharide (LPS),
which is a component of bacteria cell walls, and is most one of the most
important signals for gut health. However, it is also an integral part of our
response to any bacterial pathogen.
While I mentioned above that most of our active VD (1,25(OH)2D)
is produced in the kidneys, several other tissues express the enzyme CYP27B1,
which turns 25(OH)D into 1,25(OH)2D, which means they can also
produce active VD. It turns out
that certain immune cells will turn this pathway on when pathogen sensing
receptors like TLR4 are activated, showing that VD is an important
immunomodulator (4).
Not only do immune cells create their own active VD in
response to a pathogen, they also use the VD receptor (VDR) to regulate
inflammatory signaling, and this is especially evident in the intestinal
tract. A study that engineered
mice that had immune cells lacking VDR showed that IL-10 production, which has
been shown to decrease inflammation in IBD patients, was greatly reduced by
cells lacking VDR (5). This table shows the percentage of
cells that produced IL-10, and you can see the immense decrease in the VDR
knock-out (KO) cells.
Finally, a study in cows showed that immune cells stimulated
by LPS produce more NO (Nitric Oxide) which is thought to be a part of the
antimicrobial defenses in bovine animals (6).
When we take all this data together I think we can see what
an important role VD plays in our immune response, especially to
pathogens. We use VD to regulate
our pro and anti-inflammatory agents, and also use it to stimulate production
of defense molecules. VD is such
an important modulator of these processes that our immune cells express the
enzymes required to create active VD when needed.
How
to optimize Vitamin D status
If VD is so important to our bodies for a number of reasons,
but especially in supporting immune function, how much of it do we actually
need? And what are the best ways
to get it? Well, obviously the
best way to get VD would be through our natural creation pathways, and that
would mean you need to make sure you get enough sunlight. However, for many of us this simply
isn’t a possibility, or may not be possible even (7). Not only is VD hard to get during
several months of the year for a wide range of latitudes, many people are
incredibly deficient as it is.
This graph from a study of a Swiss population shows the serum levels of
VD during different periods of the year (8). I like this graph because it shows the
VD levels in the two most common measurement styles, ng/mL and nmol/L. Using this graph as a guide, we can
make a crude estimate that 10 ng/mL is roughly equivalent to 25 nmol/L.
This study of patients at a Chinese clinic helps us answer
that exact question (9). 22 patients were given 800 IU of
cholecalciferol, while 24 served as a control. They followed this protocol for
6 months, and found that the treated group had improved their serum VD levels
by a significant amount. The one
thing this study doesn’t tell us is during what months of the year it was
conducted. I think this is an
important factor for any study on VD status, especially as we have seen how
hard it is to naturally produce VD during the winter months in many of the
latitudes in China. However, if we
use the difference between treatment group and control as a baseline, we can
hypothesize that 800 IU of VD is good for about a 7 ng/mL increase in serum
VD. Using our conversion from
before, we can say this about a 17.5 nmol/L increase.
The final question we should ask is just what is an optimal
level of VD? Well, with many
questions like this I think the best place to look for an answer would be
traditional hunter-gatherer societies.
This is because these groups are living closest to our evolutionary
roots, and you would expect them to have the closest levels to our ancestors,
and thus be more in line with what our bodies are developed for. A soon-to-be-published study on the VD
levels of the Hadzabe and Maasai societies found the average VD levels to be
around 115 nmol/L (using our estimation that’s ~46 ng/mL) (10). I would say this is a good rough
estimate for us to shoot for, however as I said before the time of year of the
data collection would be an important variable in this study, although less so
because it was done in Africa.
Unfortunately, at this time we can’t access the data, as this is
pre-release abstract for the study.
Let’s do some hypothetical math using a wide range of
assumptions we have from the data above.
Using our Swiss population data from above we can say for a northern
latitude our VD levels are about 29 ng/mL in the summer, 22 ng/mL in the
spring/fall, and 17 ng/mL in the winter.
If we also hypothesize that an 800 IU cholecalciferol supplement is
worth about 7 ng/mL, in order to reach the hunter-gatherer level of 46 ng/mL at
all times during the year they would need to supplement with about 1943 IU in
summer, 2742 IU during the spring/fall, and a whopping 3428 IU in the winter!
As we can see vitamin D is a very important nutrient for a
wide variety of biological processes.
It is essential for calcium homeostasis, but is just as important for
immune system regulation. It can
help prime our defenses when a pathogen is sensed, and helps to control the
inflammation associated with many diseases caused by chronic low-grade
inflammation.
Vitamin D is also a nutrient that is tough to get in many
parts of he world, especially during the winter months. During these periods it is very
important to optimize vitamin D levels through supplementation, and if use
hunter-gather levels as a rough estimate of optimal levels of human vitamin D
requirements, we can see how deficient many of us probably are. I would not recommend everyone go out
and start throwing back the vitamin D capsules like candy, but I think we can
all benefit from some supplementation, especially during the cold, dark
winters!
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