Despite multiple converging lines of evidence for a higher level being better for us in
a huge variety of health areas, most governmental guidelines only recommend conservative amounts
of vitamin D that are just enough to support bone health.
Today we are going to learn how these comparatively low recommendations were arrived at and where
they originally came from.
How are ye doing guys, you're very welcome back to the vitamin D series.
Last time out we examined the multiple lines of evidence supporting a much higher vitamin
D level than that which is usually seen in the population, leading many commentators
to recommend much higher doses of vitamin D than the standard governmental guidelines
to reap these health benefits.
When beheld in totality, these lines of evidence strongly support the position that we need
lots more vitamin D for extra-skeletal health than what we need for just bone health, but
each argument has it's criticisms on an individual basis and none can prove causality on it's
own.
Because of some concerns about toxicity of higher levels of intake, authors of guidelines
that have implications for public health policy will not recommend these higher levels until
causality can be definitively proven with the gold standard of evidence - positive data
from human randomised controlled trials, or RCTs - which as we learned last time
has for some reason not emerged yet.
In other words, when we give vitamin D to people to raise their level up to this supposedly
healthier range, we don't seem to get the health benefits we would expect, and this
is why governmental guidelines still recommend lower intakes of vitamin D since cause-and-effect
with these better health outcomes has not been proven.
Vitamin D has been trialled in RCTs against a diverse range of disease states - not only
the obvious musculoskeletal diseases, but also cancer, central nervous system diseases
like multiple sclerosis, cardiovascular disease, diabetes, obesity, inflammatory bowel disease
and various other manifestations of both autoimmunity and immune function against infectious diseases.
Despite the exciting effects of vitamin D suggested by observational data and the biological
plausibility of the efficacy of the nutrient lent by the convincing pre-clinical data,
apart from the effects on bone health the results from these trials have been inconsistent
at best, and very disappointing compared to what we would expect given all the other forms
of evidence.
This divergence in results between interventional and non-interventional studies, and the weight
individual groups ascribe to each, is the main reason why there is so much disagreement
in the scientific world, even for bone health which is by far the best-established benefit,
about how much vitamin D we should be taking, and why there is so much confusion on a consumer
level about how much to take - confusion that you may well be aware of as a concerned individual
trying to decide on a vitamin D supplement.
But one thing nearly everyone agrees on is that almost everyone requires a certain minimum
amount of vitamin D - almost all guidelines are for a minimum of around 400-600 units
per day and upwards.
Let's examine this common ground first of all - how those recommending lower doses arrived
at this dosing level.
For this, we must go back to when the very first dietary guidelines for vitamin D were
released.
The process of setting dietary reference values normally originally begins with looking at
the levels seen in healthy populations without any manifestations of deficiency as they are
defined by current science.
This is an important concept to be aware of as it pertains to vitamin D especially - healthy
levels of the nutrient in question were determined first, and then we worked back from there
to quantify the correct dietary intake.
Here we can already see how this would be especially tricky for vitamin D - we can make
the nutrient ourselves on exposure to the sun, so this must be controlled for when trying
to find the right dose.
This is in addition to many other complicating factors as we shall see.
Just a quick note on units - you may have seen vitamin D doses reported both in terms
of micrograms and 'IU', short for International Units, and your vitamin D supplement may be
labelled with either.
To convert from the former to the latter, simply multiply by 40.
Similarly, you will see serum levels reported both in nanograms per millilitre and micromoles
per litre.
To convert from the former to the latter simply multiply by 2.5.
The earliest and largely non-scientific attempt at determining the appropriate level of intake
took place in the early twentieth century, and followed from the observation that the
first identified manifestation of deficiency, rickets, which was an epidemic at the time
in the industrialised world, was not observed in infants and children given one teaspoon
of cod liver oil per day, which equated to around 400 units of vitamin D. The first attempt
at scientifically reconciling deficiency and intake was performed by a group in the UK
in the 1991, who observed that rickets was seen in individuals in a small study with
serum levels between 8 and 20 ng/mL, or 20 and 50 nmol/L, with increasing severity seen
in those towards the lower end of the range.
In what would turn out to be a crucial decision for the future of vitamin D, this UK committee
appears to have acted conservatively in picking the lower end of this range as the cut-off
point, which equated more closely with the 400 units intake level that had been previously
established by the cod liver oil intake.
As tends to happen in nutritional science, each subsequent iteration of a guideline has
built strongly on the it's most recent predecessor, without examining the totality of the evidence
with new eyes, and this was the first example.
Indeed, the UK's most recent guidelines from 2016 again built upon this initial work in
the derivation of their "population-protective" recommended vitamin D levels, again based
off prevention of rickets and osteomalacia.
This early conservative estimate set a precedent for all further work by national governmental
bodies in setting their population nutrient reference values.
Over time, as not only vitamin D and nutritional science, but medical science in general evolved,
the randomised controlled trial became the gold standard for proving cause and effect
between intake of a nutrient or drug and the health effect of interest.
No longer was it acceptable to base population nutrient reference values off observations
alone.
But as we have seen earlier in the video, the evidence from randomised controlled trials
is the weakest for vitamin D, and so far no governmental body has appraised the human
interventional data as strong enough to raise the recommendation for vitamin D for the potential
extra-skeletal benefits above that which was established in the very earliest work on the
effects on bone health - and thus they have largely stayed the same ever since those very
earliest recommendations.
But plenty of public health recommendations have been formed and changed in the absence
of evidence from randomised controlled trials.
How have the extra-skeletal effects of vitamin D seemed to escape this?
Well first of all, governmental guidelines appropriately tend to be very conservative
and recommendations change very slowly over time, which is no surprise when you think
of the implications these guidelines have in terms of law, public health policy and
cost.
In a way, subsequent guidelines have been tied into these original cut-points that were
defined on what would now be seen as a very shaky foundation, and perhaps would be evaluated
completely differently now if they were starting from scratch.
We must also remember that when vitamin D was discovered, rickets and osteomalacia were
definite, quantifiable health problems.
Once vitamin D deficiency was found to be the cause of those problems, public health
authorities would have been to blame if they did not recommend enough to successfully prevent
them - this is where this original small recommended dose came from as we have seen.
In general, it is easier to blame an individual or group for causing a health problem through
their action than one resulting from their inaction.
Thus, it has been suggested that groups issuing guidelines that will affect public health
policy tend to be biased towards recommending just enough to prevent the easily quantifiable
health effects such as rickets, and accept what has been less quantifiable risk of
non-skeletal health problems as a result of their not recommending enough - rather than
the other way around.
This stance has been justified by the seven principles of public health ethics, which
classically put doing no harm above doing good - so governmental recommendations have
stuck with a level that will definitely do no harm at the expense of missing out on some
potential good.
First do no harm - primum non nocere!
All of this stems from the concern about causing toxicity and overdose by recommending too
much, and they will not recommend the higher level of vitamin D until the benefits can
be definitively proven to outweigh the risk of toxicity.
But how legitimate are these concerns about overdose?
To examine this, we must again go back to the very earliest implementation of vitamin
D supplements.
Following the discovery of the vitamin and it's anti-rickets effects, it became very
much in-vogue in the '40s and '50s, with very high doses given to infants and heavy fortification
of milk with the hope of preventing the disease with perhaps a 'more is better' approach.
Following this, a small epidemic of infantile high serum calcium emerged, linked with birth
defects and mental problems in some of those with this hypercalcaemia.
Relying on observational evidence, it was concluded at the time that these effects were
due to the over-fortification of milk with vitamin D. A subsequent hysteria of the toxicity
of vitamin D spread throughout the World, and to this day it is still taught that vitamin
D is one of the most toxic fat-soluble vitamins.
Retrospectively, aside from the high doses of vitamin D often given to infants that everyone
would agree is too much nowadays, it is likely that this infantile hypercalcaemia occurred
because of rare mutations in one of the enzymes that allow us to regulate the amount of active
vitamin D, and the birth defects were due to an even rarer genetic disorder.
Regardless, the precedent had been set to be extremely cautious with vitamin D recommendations,
and err towards recommending the minimum amount possible.
I will be fully exploring vitamin D toxicity and overdose before we finish out the series,
but suffice to say for now it does remain a relatively under-explored area, in no small
part because it is so uncommon, and assuaging concerns scientifically about toxicity at
the higher recommended doses will still not be enough on it's own to get governmental
advice to change while they are at this comfortable level.
All these features have set the stage for conservative authors to stick firmly with
their recommendations of just enough vitamin D to prevent bone disease and no more, until
the extra-skeletal effects can be proven.
And this could be seen as reasonable - as we have explored up until now in the vitamin
D series, giving vitamin D to people to get them up to these higher blood levels does
not seem to improve their health, and when it comes down to it we are not interested
in theoretical pathways or effects on animals or observations or appeals to nature or post-mortem
markers of bone health or maximal PTH suppression - the only thing we are interested in is improving
people's health, and vitamin D does not seem to be able to do that when put to the test
in randomised controlled trials.
Overall, in this video we have determined how the level universally accepted by all
authors as an absolute minimum dose was arrived at following the very earliest work on vitamin
D.
We have also examined the rationale behind why conservative authors do not recommend
anything above this minimum level.
But are these conservative guidelines right?
Next time around we will be examining the controversy that has emerged between these
conservative authors and those who recommend a lot more vitamin D. But either way, regardless
of where you stand on how much weight you put on the causal evidence and how much you put
on the observational and mechanistic data, in a way, our modern recommendations can have
their roots traced back all the way to the finding that a teaspoon of cod liver oil seemed
to be enough to prevent rickets.
Perhaps not the most scientific of determinations!
In summary, almost all authors recommend a minimum of around 400-600 units of vitamin
D per day and upwards.
This amount was determined following the very earliest work on vitamin D. Since then, multiple
converging lines of evidence have emerged to convince many to recommend much more vitamin
D than this.
However, the most conservative and influential authors will not recommend these higher levels
until the beneficial effects can be proven using randomised controlled trials.
Stick around for part 5 when I will be directly comparing the approaches of these two contrasting
viewpoints.
Talk to ye soon guys, Sláinte!