Many people take their vitamin D every day or every week.
But sometimes an entire year's supply of vitamin D is given in one single massive dose, and
lots of frequencies in between have also been tried.
Is there any evidence to tell us how often we should take vitamin D for optimal health?
Is daily better or weekly?
Watch on to find out!
How are ye doing guys, and welcome back to the vitamin D series.
We finally got as far as the derivation of my unbespoke recommended daily dose of vitamin
D of 3000 units in my last video.
But another aspect of vitamin D posology that you guys have been interested to know about
is dosing frequency - is it okay to take our daily 3000 units all in one go once a week
or once a month, for example?
This is certainly a common practice with other commonly-supplemented nutrients like vitamin
B12.
Actually, this is a practice I don't recommend for B12, and I recommend at least daily or
even multiple times daily dosing for this nutrient as I have discussed before in my
B12 series.
But what about vitamin D - is it okay to take big doses infrequently for this nutrient?
Intuitively, you might understand the answer to be "no."
Our bodies can go prolonged intervals without taking in most nutrients - obviously we animals
have to be able to deal with periods of time without access to certain foods for example,
and so most essential nutrients don't have to be taken in every single day for optimal
functioning.
But as I discussed right back at the start of this series, vitamin D is not a nutrient,
it is a hormone - and we did evolve getting a steady, constant dose of it every day because
we can produce it ourselves under optimal conditions, and unlike food-borne nutrients
we were guaranteed exposure to enough sunlight for maximal vitamin D production every single
day that didn't even fluctuate much in intensity throughout the year.
Don't underestimate the importance of something that has been a part of our daily lives until
very recently on an evolutionary scale.
The fact that in the wild we produced a steady amount of vitamin D every day would lead one
to believe that the optimal dosing frequency for getting it in supplement form would also
be daily.
But this is just speculation, and there are many leaps of logic made in this argument.
Sunshine vitamin D is not the same as the supplemental form.
So what does the science say about dosing frequency?
Let's start with the extreme case of yearly dosing - what potential problems might occur
here?
First of all, it is known that the annual fluctuations in our own natural production
brought about by the changing of seasons is enough to cause health effects, such as weaker
bones towards the end of the Winter and possibly increased susceptibility to viral infections.
Remember, this is why we want to supplement vitamin D in the first place!
But at least in this case when we are making vitamin D, it is spread out throughout Spring
and Summer - we do not synthesise our entire year's supply of vitamin D on one day.
So what happens if we do - what happens if we condense this seasonal fluctuation of vitamin
D production into one day vs. 364, rather than Spring/Summer vs. Autumn/Winter?
As would be expected, despite this latter approach actually giving us enough vitamin
D overall unlike sporadic sun exposure, there appear to be some additional negative health
effects with it.
Yearly doses are given starting at around a half a million units and upwards, with at
least a million units being required to hit my recommended 3000 units per day.
But the total binding capacity for vitamin D by it's specific carrier protein in the
blood is only around 200,000 units, resulting in the highly non-physiological situation
emerging where large amounts of unbound or albumin-bound vitamin D are circulating in
the blood.
It is this free fraction that is biologically active, and so given that this practice would
result in far more free vitamin D than what would ever be seen in nature it makes sense
that this situation would result in toxicity and disrupted physiology despite the overall
daily dose being the same.
The approximately 90,000 units required for monthly doses would likely still exceed the
binding capacity freed up by the end of the month, but even if it does not, doses on the
order of tens of thousands of units would still be expected to displace other metabolites
like the active form from the vitamin D binding protein and interfere with normal physiology
that way, disrupting the delicate homeostasis that is going on in the vitamin D signalling
system.
These doses would also still be enough to potentially trick our cells into upregulating
the enzyme that breaks down active vitamin D, hypothetically causing paradoxical deficiency
at the cellular level.
These are some of the proposed reasons why monthly and upwards dosing intervals of vitamin
D have been found time and again to produce negative health consequences when compared
with the same overall dose given more frequently, such as increased risk of falls and fractures
- I discussed this concept previously in my video on why vitamin D RCTs have failed to
show benefit, which often use these long-interval dosing regimens for cost and double-blinding
purposes.
But this is where things start to become less black-and-white - when we get down as far
as weekly dosing.
The negative health consequences of longer intervals have not been seen with weekly dosing
vs. daily, but going beyond the intuitive understanding that vitamin D should be taken
daily as I mentioned at the start of the video, there are still a number of proposed mechanisms
by which this practice might not be optimal. 25-hydroxyvitamin D, the so-called 'storage'
form of the hormone that is formed following the first step of activation by the liver,
would not be expected to fluctuate on taking vitamin D weekly.
However, there is a lot more to having a stable vitamin D physiology than having a stable
25-hydroxy level.
Indeed, this may be one of the worst markers of stable vitamin D activity, since it was
chosen as a biomarker of vitamin D status for the very reason that it doesn't fluctuate
very much in relation to acute endogenous synthesis or oral intake.
It is an important part of the story, but it's not the whole story.
Unactivated vitamin D itself may also be biologically relevant, and since this non-hydroxylated
form has a half-life of only around one day, weekly dosing certainly would cause large
fluctuations of this intermediate, leading some experts to recommend daily dosing.
This is especially convincing when you consider that many, if not most cells, most famously
immune cells, have the ability to locally activate vitamin D without depending on the
classical endocrine signalling pathway involving the liver and kidneys, and indeed that may
be the source of the majority of the active vitamin D in these cells.
With that in mind, a fluctuating unhydroxylated vitamin D level could not be seen as the optimal
situation.
This has led some to recommend vitamin D itself as the biomarker of choice rather than it's
25-hydroxylated form - since the former would also reflect stable intake as well as overall
adequate intake.
So here we can see a kind of a hierarchy emerge - weekly doses result in fluctuating unactivated
vitamin D levels that are at least theoretically not optimal, monthly doses are where we start
to see definite negative health consequences like increased risk of falls, dosing every
few months would require doses high enough to displace intermediates from the vitamin
D binding protein, and yearly megadoses would be enough to result in large amounts of unbound
vitamin D and it's metabolites circulating in the blood.
And at each increasing dosing interval you of course keep all the downsides from the
level below it in this hierarchy.
Seemingly the more frequently you take your vitamin D the better, up to somewhere around
weekly to daily.
So to take this concept to it's logical conclusion, is there anything to be said for multiple-daily
dosing - taking vitamin D more often than once per day?
Remember, I'm not suggesting that daily dosing of oral vitamin D is totally optimal either
- as we have explored throughout this series, getting vitamin D via the oral route instead
of naturally from the sun initially bypasses direct binding with vitamin D's specific carrier
protein and results in a rapid but less sustained serum level of the unhydroxylated nutrient.
But this is not going to improve much by taking it any more frequently than daily because
doses on the order of 3000 units per day are not going to cause these massive spikes in
level we see here with 10,000 and 25,000 units anyway, and if taken every day, given it's
half-life of around 24 hours a steady state will be achieved that will largely eliminate
these big troughs anyway.
Especially when you consider that normal physiology with adequate sun exposure would provide us
with a fresh pulse of vitamin D every day when the sun comes up, I think daily dosing
is the sweet spot for supplementing as well.
There just isn't as much to gain with a multiple-daily dosing nor a reasonable physiological basis
like there potentially could be with vitamin B12.
This is also why I favour taking your vitamin D in the morning - I couldn't find any firm
data on when is the best time of day to take it apart from a possible negative correlation
between vitamin D level and melatonin, and some anecdotal reports of reduced sleep quality
on taking vitamin D late in the day, but once again, intuitively it just makes sense to
pulse your serum unhydroxylated vitamin D concentration at the same time this would
occur naturally - in other words, early in the day when we would be exposed to the sun.
So there you have it guys, my recommendations on how often to take vitamin D. I do not recommend
the long dosing intervals of monthly and above because of both sensible proposed mechanisms
of toxicity and negative results from RCTs.
The science is less clear-cut on if taking it daily is any better than weekly, but many
experts recommend daily based on the relatively short half-life of unhydroxylated vitamin
D in the blood, and I am inclined to agree with this line of reasoning and take it daily
myself.
Still less clear-cut is what time of day to take it - but again, personally I go with
the more intuitively natural option of early in the day, a practice backed up by anecdotes
of better sleep, and so this is what I recommend.
But of course the best time of day and best dosing interval to use are the ones you will
actually stick to!
I hope this helps you guys that were wondering about dosing frequency, next time out we'll
be looking at vitamin D form - comparing D2 with D3, differing formulations and analogs.
Talk to ye then guys, sláinte!