May 21, 2025 • 20 mins
Vitamin D recommendations in 1941 began this debate. Over the years, updated guidelines have continued to spark controversy and debate in the field of vitamin D research.
In this episode of Daily Value, we look at the recent “Vitamin D-ilemma” reinvigorated by the Endocrine Society's updated 2024 guidelines. These new recommendations have dialed back routine testing and supplementation targets, igniting pushback from leading researchers who argue we might be overlooking significant health benefits (including reduced risks for 8 out of the top 10 leading causes of death). Join us as we Look at the evolving science behind vitamin D, why randomized trials and observational studies seem to tell different stories, and how you can practically navigate these conflicting recommendations to optimize your own health.
00:00 Introduction: The Vitamin D Controversy
01:00 Historical Guidelines and Shifts
01:54 The 2011 Guidelines and Their Impact
03:57 The 2024 Update: A New Debate
06:13 Understanding Vitamin D's Role in the Body
07:29 Clinical Trials vs. Observational Studies
09:13 Health Benefits of Higher Vitamin D Levels
11:58 Challenges in Vitamin D Research
15:56 Practical Recommendations for Optimal Vitamin D
19:32 Conclusion: Striving for Optimal Health
PMID: 39861407
PMID: 38828961
PMID: 37004709
PMID: 30992519
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:00):
What if the latest health guidelines are steering
us away from one of our mostaccessible tools for preventing
disease, one that someresearchers have come out and
claimed could significantlyreduce the risk for 8 out of the
top 10 leading causes of death?
Vitamin D recommendations haveshifted dramatically the past
year, with the endocrine societynow questioning the benefit of
(00:21):
routine testing and higher dosesupplementation for most healthy
adults.
But why the sudden change, anddoes the science really support
this conservative approach?
Today, we'll dive into bothsides of this controversial
update.
What does the latest evidencetruly say about optimal vitamin
D levels, and might we bemissing something critically
important?
(00:42):
Let's find out on episode 45 ofDaily Value.
Hello everyone, welcome back toDaily Value.
I'm William Wallace, and todaywe're exploring the current
vitamin D controversy.
That is, how much do we reallyneed?
(01:03):
The first official vitamin Dguideline appeared back in 1941,
setting a daily dose around 400international units, or IUs as
I will call them.
This was enough to preventrickets based on observations
with cod liver oil.
For decades afterward, thisrecommendation remained largely
unchanged, based more onguesswork than actual, rigorous
data.
In 1997, the guidelines shiftedfrom a formal recommended
(01:29):
dietary allowance, or RDA, toinadequate intake, or AI, which
is used when there isn't enoughevidence to set an RDA.
Researchers identified25-hydroxyvitamin D as the key
marker of vitamin D status,status and early dose response.
Studies suggested that at least5,000 international units or
IUs a day might be needed, yetthe clinical understanding was
(01:52):
still largely limited to bonehealth.
A major shift occurred in 2011when the Institute of Medicine,
now the National Academy ofMedicine, updated guidelines.
After an extensive review, theyconcluded evidence linking
vitamin D supplementation tohealth benefits beyond was
inconsistent.
Thus, they set an REA at 600international units or IUs a day
(02:15):
, also expressed as 15micrograms for most adults, with
a goal serum level of 20nanograms per milliliter,
equivalent to 50 nanomoles perliter, and increased it to 800
IUs a day or 20 micrograms forolder adults.
However, these recommendationsquickly sparked debate.
Later in 2011, the EndocrineSociety issued dramatically
(02:37):
different guidelinesrecommending serum levels of 30
nanograms per milliliter or 75nanomoles per liter or higher,
and daily vitamin doses.
Later in 2011, the EndocrineSociety issued dramatically
different guidelinesrecommending serum levels of 30
nanograms per milliliter or 75nanomoles per liter or higher,
and daily doses of vitamin Dbetween 1,500 and 2,000 IUs a
(03:01):
day, with short-term doses up to10,000 IUs a day for correcting
deficiencies.
They also suggested potentialextra-skeletal benefits,
including lower risk of cancer,heart disease, falls and
depression, though clinicaltrial support for these outcomes
was limited at the time.
The Endocrine Societyguidelines inadvertently
increased demand for widespreadvitamin D testing and higher
(03:24):
dose supplements.
Soon, some researchers arguedfor even higher optimal serum
levels, between 40 and 80nanograms per milliliter, and
doses nearing 10,000 IUs a daywould be needed.
Despite controversy aroundthese higher targets, many
international health authoritiescontinue recommending modest
intakes between 400 and 800 IUsof vitamin D daily, focusing
(03:48):
strictly on bone health.
Today, vitamin D deficiencyremains widespread globally,
affecting around 45% of theglobal population.
Against this backdrop, theEndocrine Society's recent 2024
update has reignited the debate,once again challenging
conventional wisdom about howmuch vitamin D we really need In
2024,.
(04:10):
So just last year, theEndocrine Society published
updated vitamin D guidelines,significantly changing their
prior stance.
Previously, the EndocrineSociety defined vitamin D
deficiency as serum 25-hydroxyvitamin D levels below 20 ng per
mL, insufficiency between 21and 29 ng per mL and sufficiency
(04:30):
between 30 to 100 ng per mL.
But now the Endocrine Societyno longer endorses these older
definitions.
Their latest guidelines arguethat current clinical evidence
doesn't clearly support specificvitamin D thresholds for
healthy individuals.
Specifically, they claimthere's no clear evidence from
randomized controlled trialsthat supplementing to reach a
(04:51):
25-hydroxyvitamin D level of 30nanograms per milliliter or
higher provides meaningfulhealth benefits compared to
lower levels like those set bythe National Academy of Medicine
at 20 nanograms per milliliter.
This update triggeredconsiderable debate.
In fact, a consensus statementfrom 27 leading researchers on
(05:12):
vitamin D sharply contrasts thenew Endocrine Society
recommendations.
This group emphasized evidencefrom multiple analyses
suggesting that maintaining a25-hydroxyvitamin D
concentration of 30 to 50nanograms per milliliter might
significantly reduce risks ofcancers, autoimmune diseases,
cardiovascular events, diabetes,respiratory infections and even
(05:35):
improve outcomes related toCOVID-19.
These experts stronglysupported daily supplementation
with up to 2,000 IUs a day toconsistently achieve these
higher serum levels,highlighting potential health
improvements far beyond bonehealth alone.
Critics argue the latestendocrine society guidelines are
overly cautious, narrowlyfocusing on bone health outcomes
(05:56):
, while disregarding a growingbody of data suggesting broader
health benefits, includingimmunity, cardiovascular health.
And with these sharplycontrasting perspectives, the
question remains are the newguidelines appropriately
cautious or could theyinadvertently dismiss important
health benefits?
To understand why there's suchdebate around optimal vitamin D
(06:17):
levels, it helps to look at howvitamin D actually works in the
body, and indeed it works manydifferent ways, but vitamin D
itself isn't active until it'sconverted into its active
hormone form called calcitriol.
Calcitriol binds directly tovitamin D receptors inside cells
, influencing gene expression.
Vitamin D itself isn't activeuntil it's converted into its
(06:39):
active hormone form calledcalcitriol.
Calcitriol binds directly tovitamin D receptors inside cells
, influencing the expression ofhundreds of genes, turning some
genes on and others off.
In one very interesting study,healthy adults supplemented with
vitamin D doses of 600 IUs,4,000 IUs or 10,000 IUs per day
(07:01):
for six months showed dramaticdifferences in gene expression.
At the lowest dose, 162 geneschanged expression.
At medium doses, 320, and athigh doses, a remarkable 1,289
genes changed their activity.
This clearly shows that highervitamin D levels significantly
impact gene regulation,potentially explaining broader
(07:24):
health benefits observed in manystudies, typically
observational in nature.
To this point, despite thiscompelling biology, randomized
controlled trials the goldstandard for clinical evidence
have generally struggled todemonstrate clear benefits from
vitamin D supplements.
But there's probably a goodreason why the evidence-based
(07:44):
pyramid of evidence was designedto study drugs on an
intention-to-treat basis.
Clinical trials designed forpharmaceuticals don't work well
for nutrients like vitamin D,because everyone has some
baseline vitamin D already fromdiet, sunlight or existing
supplementation.
Existing supplementation Mostvitamin D trials have enrolled
(08:06):
participants who already haverelatively high levels, around
30 ng per mL or above, wherefurther supplementation may have
limited additional benefit.
On top of that, many trialshave used relatively low doses
of vitamin D or allowed theplacebo group to also take small
doses, which muddy the resultsa bit.
This poor design makes itnearly impossible to clearly
detect benefits.
(08:26):
On the other hand,observational studies, where
researchers track people'svitamin D levels and health
outcomes over time, consistentlyshow significant benefits at
higher vitamin D levels.
While observational studieshave limitations, such as the
potential for confoundingfactors and the natural
variability of vitamin D levelsover time, it has been suggested
by many that they are moreeffective at capturing vitamin
(08:48):
D's true impact on healthoutcomes, especially when paired
with evidence from studiesexploring biological mechanisms.
Together, these challenges andlimitations explain why the
controversy around vitamin Dsupplementation continues and
why both researchers andclinicians remain divided over
how much vitamin D is trulyoptimal.
Observational researchconsistently shows vitamin D
(09:10):
influences health acrossmultiple body systems.
Higher serum vitamin D levels,specifically concentrations
above 30 nanograms permilliliter, are linked to
significantly reduced riskfactors for many major diseases
and mortality.
For cardiovascular disease,higher vitamin D status
correlates with a decreased riskof hypertension, heart attacks
(09:30):
and overall cardiovascular death.
For instance, individuals withvitamin D status correlates with
a decreased risk ofhypertension, heart attacks and
overall cardiovascular death.
For instance, individuals withvitamin D deficiency had nearly
double the risk ofcardiovascular mortality
compared to those withsufficient levels.
For stroke, observationalstudies suggest a strong inverse
relationship between vitamin Dlevels and stroke risk, with
significant protective effectsobserved particularly above 30
(09:51):
ng per mL threshold.
For cancer, extensive studiesindicate that adequate vitamin D
can lower cancer risksignificantly.
Higher serum concentrationsaround 40 ng per mL or above
show promise in reducing theincidence of colorectal and
breast cancer by as much as20-30%.
For immune health, vitamin Dsupports immune system function,
(10:14):
reducing inflammation byinhibiting the action of T
helper cells 1 and 17, whichdrive inflammation in autoimmune
conditions and allergies.
Vitamin D potentially decreasessusceptibility to respiratory
infections, including COVID-19.
Higher vitamin D levelscorrelate with better infection
outcomes, reducedhospitalization rates and
decreased severity ofrespiratory illnesses.
(10:37):
For dementia and Alzheimer'sdisease, lower vitamin D levels
are linked with increased riskof dementia and cognitive
decline.
Studies suggest maintaininglevels above 30 nanograms per
milliliter could substantiallyreduce this risk.
For diabetes, vitamin D plays arole in glucose metabolism,
(10:57):
insulin sensitivity and may helpdelay the progression from
prediabetes to type 2 diabetes.
Achieving and maintainingvitamin D levels between 40 and
50 nanograms per milliliter maysignificantly cut diabetes risk.
Lastly, pregnancy and birthoutcomes.
Adequate vitamin D statusduring pregnancy lowers risk for
gestational diabetes,preeclampsia and preterm births.
(11:20):
Levels above 40 nanograms permilliliter are particularly
beneficial in significantlyreducing these risks.
Per the data that we're goingover.
Despite this data, most clinicaltrials, due to their flawed
designs, haven't capturedvitamin D's potential
effectively.
Participants often startedtrials already above the
(11:40):
protective threshold or receivedinsufficient doses, which
dilutes results.
In short, while randomizedclinical trials struggle to
demonstrate clear benefits dueto methodological issues,
observational and mechanisticstudies consistently indicate
substantial health benefits athigher vitamin D levels.
Given the robust body ofobservational and mechanistic
(12:00):
data, you might wonder whyguidelines from authoritative
bodies like the EndocrineSociety remain so conservative.
One primary reason is theirstrict reliance on randomized
controlled trials, or RCTs.
Rcts are considered the goldstandard in clinical evidence,
favored because theytheoretically remove bias and
clearly link interventions withoutcomes.
(12:21):
Unfortunately, as we discussedearlier, rcts designed for
pharmaceutical drugs are notwell-suited to study nutrients
like vitamin D.
This by itself could be its ownseries of episodes that we do
hear down the road.
Participants frequently starttrials with adequate baseline
vitamin D levels receive dosestoo low to make a difference, or
(12:43):
control groups are allowedadditional supplementation, all
of which dilute potentialeffects.
Another factor is what's knownas epistemic humility.
That's a cautious scientificstance recently emphasized by
the Endocrine Society in their2024 update.
Epistemic humility acknowledgesuncertainty in interpreting
existing evidence.
(13:03):
The Endocrine Society arguesthat without strong, consistent
results from multiple RCTs, thatendorsing widespread
supplementation at higher dosesmight be premature or even risky
, particularly given thehistorical tendency to overhype
nutritional interventions.
And they're not wrong there.
These guideline committeestraditionally focus on direct,
(13:25):
easily measurable outcomes likefractures, rather than broader
health markers such as immunefunction or long-term chronic
disease prevention.
Since many benefits from highervitamin D levels, like reduced
cancer or dementia risks,manifest slowly over years,
they're harder to confirmconclusively in very short-term
trials, like most RCTs.
(13:45):
Consequently, even thoughobservational studies,
biological mechanisms andmeta-analyses suggest
significant potential benefits,major health organizations
remain reluctant to increaserecommended vitamin D levels
until RCT evidence becomesundeniably clear.
This tension leaves us withconservative guidelines that may
fail to fully reflect thebroader health benefits that the
(14:08):
observational and mechanisticdata do strongly imply.
Not everyone accepts theEndocrine Society's conservative
stance.
Following their 2024 guidelines,dr Michael Holick, a prominent
and polarizing vitamin Dresearcher.
He helped identify how vitaminD is produced in the skin via
UVB radiation and advocated forits broader importance beyond
(14:30):
rickets, in areas like immunityand chronic disease.
He published a strongcounter-statement arguing that
these guidelines ignore evidencesupporting higher vitamin D
levels.
Hollick emphasized 20significant health outcomes that
improve, notably at vitamin Dconcentrations above specific
thresholds.
Above 60 nanograms permilliliter.
(14:50):
Reduced the risk ofpreeclampsia in some studies.
Above 50 nanograms permilliliter.
Reduced the risk ofpreeclampsia in some studies.
Above 50 nanograms permilliliter.
Reduced the progression frompre-diabetes to type 2 diabetes
and lowered breast cancerincidence.
Above 40 nanograms permilliliter.
Decreased risks of autoimmunedisorders, cesarean section
births, infant dental caries,digestive cancer relapses,
(15:11):
multiple sclerosis and prematurebirths.
At above 30 nanograms permilliliter.
Significant reductions incancer mortality, cardiovascular
mortality, colon cancer,covid-19 mortality, respiratory
distress syndrome, osteomalaciaand upper respiratory tract
infections.
The data that Hollis citedsuggests that 30 nanograms per
(15:33):
milliliter should represent abare minimum target for serum
vitamin D, with 40 nanograms permilliliter or higher being
optimal to ensure broaderprotection across multiple
health outcomes.
Hollis and other researchers'point was this by setting
thresholds too low, currentguidelines might inadvertently
overlook important achievablehealth benefits supported by a
(15:54):
growing body of research.
Given these complexities, thepractical question becomes how
do we safely and effectivelyachieve optimal vitamin D levels
?
Supplementation remains themost efficient and reliable
method for consistentlyincreasing serum vitamin D
concentrations.
Vitamin D supplementation witharound 2,000 IUs effectively
(16:14):
raises serum 25-hydroxy vitaminD above 30 nanograms per
milliliter in 90% of adults andcomfortably maintains these
levels in most people.
To achieve even higherprotective levels of 40 to 70
nanograms per milliliter, adaily dose between 4,000 and
6,000 IUs of vitamin D3 havebeen recommended.
(16:36):
But what about vitamin D fromsun exposure?
Sunlight naturally triggersvitamin D synthesis in the skin,
but effective and safe exposuredurations vary significantly
based on the season, locationand skin type.
Research conducted inSwitzerland illustrates this
clearly.
In spring and summer months,about 10 to 15 minutes of midday
sun exposure to approximately22% of uncovered skin, such as
(17:01):
arms, face and neck, is enoughto produce around 1,000 IUs of
vitamin D without significantlyincreasing risk of sunburn or
erythema.
However, during autumn andwinter, particularly at northern
latitudes, the requiredexposure can skyrocket to
several hours, often making itimpractical or unsafe due to
(17:21):
sunburn risk and coldertemperatures, while modest
exposure about 10-15 minutesdaily in warmer seasons can
substantially boost vitamin Dlevels safely.
Relying exclusively on sunlightis usually insufficient during
colder months or cloudy periods,making supplementation a
valuable tool.
But what about safety at highersupplement doses?
(17:43):
The official tolerable upperlimit for vitamin D intake is
set at 4,000 IUs a day,representing the highest daily
intake that is unlikely to poserisks of toxicity for most
adults intake that is unlikelyto pose risks of toxicity for
most adults.
Originally, the tolerable upperlimit was considered at 10,000
IUs a day, but was reduced dueto limited toxicity data from
case reports involving extremelyhigh doses, up to 40,000 IUs
(18:07):
per day, which can lead tocomplications such as elevated
calcium levels or kidney stones.
Vitamin D toxicity largelymanifests as calcium toxicity
because vitamin D increasescalcium uptake in the intestines
.
It's important to note thatmost data suggests signs of
calcium toxicity tend not tomanifest up until someone
reaches around 150 nanograms permilliliter, equivalent to 375
(18:31):
nanomoles per liter.
Within the body ofobservational data we looked at
today, the potential benefittapers off around 80 nanograms
per milliliter, equivalent to200 nanomoles per liter.
The recent rebuttal to theEndocrine Society suggests that
maintaining serum hydroxyvitamin D concentrations within
a protective range, ideallybetween 40 and 70 nanograms per
(18:53):
milliliter, using dailysupplementation of 2,000 to
6,000 IUs a day, combined withsensible, modest sun exposure in
summer months, is a balancedand safe approach supported by
the current evidence.
Is this range really desirablefor most people?
Well, I'll give you my opinion.
I agree with the datasupporting safety with vitamin D
(19:13):
levels between 40 and 70nanograms per milliliter,
assuming that people haveoptimal conutrient status of
things like vitamin K andmagnesium.
That being the case, it doesn'thurt most of us to be in that
range, and there is compelling,albeit controversial, evidence
that range may be optimal forreduced disease risk.
The bottom line guidelines willcontinue evolving, but your
(19:36):
health choices don't have toswing wildly with them.
Consider testing your vitamin Dlevels, discuss these targets
with your healthcare providerand ensure your approach to
vitamin D is informed, balancedand evidence-driven, because
ultimately, the goal isn't justto avoid deficiency, like is the
goal of current recommendations.
(19:56):
It's to achieve optimal health.
Thank you for tuning in to thisepisode of Daily Value.
Until next time, keepquestioning, stay informed and
always value your health.
What if the latest health guidelines are steering
us away from one of our mostaccessible tools for preventing
disease, one that someresearchers have come out and
claimed could significantlyreduce the risk for 8 out of the
top 10 leading causes of death?
Vitamin D recommendations haveshifted dramatically the past
year, with the endocrine societynow questioning the benefit of
(00:21):
routine testing and higher dosesupplementation for most healthy
adults.
But why the sudden change, anddoes the science really support
this conservative approach?
Today, we'll dive into bothsides of this controversial
update.
What does the latest evidencetruly say about optimal vitamin
D levels, and might we bemissing something critically
important?
(00:42):
Let's find out on episode 45 ofDaily Value.
Hello everyone, welcome back toDaily Value.
I'm William Wallace, and todaywe're exploring the current
vitamin D controversy.
That is, how much do we reallyneed?
(01:03):
The first official vitamin Dguideline appeared back in 1941,
setting a daily dose around 400international units, or IUs as
I will call them.
This was enough to preventrickets based on observations
with cod liver oil.
For decades afterward, thisrecommendation remained largely
unchanged, based more onguesswork than actual, rigorous
data.
In 1997, the guidelines shiftedfrom a formal recommended
(01:29):
dietary allowance, or RDA, toinadequate intake, or AI, which
is used when there isn't enoughevidence to set an RDA.
Researchers identified25-hydroxyvitamin D as the key
marker of vitamin D status,status and early dose response.
Studies suggested that at least5,000 international units or
IUs a day might be needed, yetthe clinical understanding was
(01:52):
still largely limited to bonehealth.
A major shift occurred in 2011when the Institute of Medicine,
now the National Academy ofMedicine, updated guidelines.
After an extensive review, theyconcluded evidence linking
vitamin D supplementation tohealth benefits beyond was
inconsistent.
Thus, they set an REA at 600international units or IUs a day
(02:15):
, also expressed as 15micrograms for most adults, with
a goal serum level of 20nanograms per milliliter,
equivalent to 50 nanomoles perliter, and increased it to 800
IUs a day or 20 micrograms forolder adults.
However, these recommendationsquickly sparked debate.
Later in 2011, the EndocrineSociety issued dramatically
(02:37):
different guidelinesrecommending serum levels of 30
nanograms per milliliter or 75nanomoles per liter or higher,
and daily vitamin doses.
Later in 2011, the EndocrineSociety issued dramatically
different guidelinesrecommending serum levels of 30
nanograms per milliliter or 75nanomoles per liter or higher,
and daily doses of vitamin Dbetween 1,500 and 2,000 IUs a
(03:01):
day, with short-term doses up to10,000 IUs a day for correcting
deficiencies.
They also suggested potentialextra-skeletal benefits,
including lower risk of cancer,heart disease, falls and
depression, though clinicaltrial support for these outcomes
was limited at the time.
The Endocrine Societyguidelines inadvertently
increased demand for widespreadvitamin D testing and higher
(03:24):
dose supplements.
Soon, some researchers arguedfor even higher optimal serum
levels, between 40 and 80nanograms per milliliter, and
doses nearing 10,000 IUs a daywould be needed.
Despite controversy aroundthese higher targets, many
international health authoritiescontinue recommending modest
intakes between 400 and 800 IUsof vitamin D daily, focusing
(03:48):
strictly on bone health.
Today, vitamin D deficiencyremains widespread globally,
affecting around 45% of theglobal population.
Against this backdrop, theEndocrine Society's recent 2024
update has reignited the debate,once again challenging
conventional wisdom about howmuch vitamin D we really need In
2024,.
(04:10):
So just last year, theEndocrine Society published
updated vitamin D guidelines,significantly changing their
prior stance.
Previously, the EndocrineSociety defined vitamin D
deficiency as serum 25-hydroxyvitamin D levels below 20 ng per
mL, insufficiency between 21and 29 ng per mL and sufficiency
(04:30):
between 30 to 100 ng per mL.
But now the Endocrine Societyno longer endorses these older
definitions.
Their latest guidelines arguethat current clinical evidence
doesn't clearly support specificvitamin D thresholds for
healthy individuals.
Specifically, they claimthere's no clear evidence from
randomized controlled trialsthat supplementing to reach a
(04:51):
25-hydroxyvitamin D level of 30nanograms per milliliter or
higher provides meaningfulhealth benefits compared to
lower levels like those set bythe National Academy of Medicine
at 20 nanograms per milliliter.
This update triggeredconsiderable debate.
In fact, a consensus statementfrom 27 leading researchers on
(05:12):
vitamin D sharply contrasts thenew Endocrine Society
recommendations.
This group emphasized evidencefrom multiple analyses
suggesting that maintaining a25-hydroxyvitamin D
concentration of 30 to 50nanograms per milliliter might
significantly reduce risks ofcancers, autoimmune diseases,
cardiovascular events, diabetes,respiratory infections and even
(05:35):
improve outcomes related toCOVID-19.
These experts stronglysupported daily supplementation
with up to 2,000 IUs a day toconsistently achieve these
higher serum levels,highlighting potential health
improvements far beyond bonehealth alone.
Critics argue the latestendocrine society guidelines are
overly cautious, narrowlyfocusing on bone health outcomes
(05:56):
, while disregarding a growingbody of data suggesting broader
health benefits, includingimmunity, cardiovascular health.
And with these sharplycontrasting perspectives, the
question remains are the newguidelines appropriately
cautious or could theyinadvertently dismiss important
health benefits?
To understand why there's suchdebate around optimal vitamin D
(06:17):
levels, it helps to look at howvitamin D actually works in the
body, and indeed it works manydifferent ways, but vitamin D
itself isn't active until it'sconverted into its active
hormone form called calcitriol.
Calcitriol binds directly tovitamin D receptors inside cells
, influencing gene expression.
Vitamin D itself isn't activeuntil it's converted into its
(06:39):
active hormone form calledcalcitriol.
Calcitriol binds directly tovitamin D receptors inside cells
, influencing the expression ofhundreds of genes, turning some
genes on and others off.
In one very interesting study,healthy adults supplemented with
vitamin D doses of 600 IUs,4,000 IUs or 10,000 IUs per day
(07:01):
for six months showed dramaticdifferences in gene expression.
At the lowest dose, 162 geneschanged expression.
At medium doses, 320, and athigh doses, a remarkable 1,289
genes changed their activity.
This clearly shows that highervitamin D levels significantly
impact gene regulation,potentially explaining broader
(07:24):
health benefits observed in manystudies, typically
observational in nature.
To this point, despite thiscompelling biology, randomized
controlled trials the goldstandard for clinical evidence
have generally struggled todemonstrate clear benefits from
vitamin D supplements.
But there's probably a goodreason why the evidence-based
(07:44):
pyramid of evidence was designedto study drugs on an
intention-to-treat basis.
Clinical trials designed forpharmaceuticals don't work well
for nutrients like vitamin D,because everyone has some
baseline vitamin D already fromdiet, sunlight or existing
supplementation.
Existing supplementation Mostvitamin D trials have enrolled
(08:06):
participants who already haverelatively high levels, around
30 ng per mL or above, wherefurther supplementation may have
limited additional benefit.
On top of that, many trialshave used relatively low doses
of vitamin D or allowed theplacebo group to also take small
doses, which muddy the resultsa bit.
This poor design makes itnearly impossible to clearly
detect benefits.
(08:26):
On the other hand,observational studies, where
researchers track people'svitamin D levels and health
outcomes over time, consistentlyshow significant benefits at
higher vitamin D levels.
While observational studieshave limitations, such as the
potential for confoundingfactors and the natural
variability of vitamin D levelsover time, it has been suggested
by many that they are moreeffective at capturing vitamin
(08:48):
D's true impact on healthoutcomes, especially when paired
with evidence from studiesexploring biological mechanisms.
Together, these challenges andlimitations explain why the
controversy around vitamin Dsupplementation continues and
why both researchers andclinicians remain divided over
how much vitamin D is trulyoptimal.
Observational researchconsistently shows vitamin D
(09:10):
influences health acrossmultiple body systems.
Higher serum vitamin D levels,specifically concentrations
above 30 nanograms permilliliter, are linked to
significantly reduced riskfactors for many major diseases
and mortality.
For cardiovascular disease,higher vitamin D status
correlates with a decreased riskof hypertension, heart attacks
(09:30):
and overall cardiovascular death.
For instance, individuals withvitamin D status correlates with
a decreased risk ofhypertension, heart attacks and
overall cardiovascular death.
For instance, individuals withvitamin D deficiency had nearly
double the risk ofcardiovascular mortality
compared to those withsufficient levels.
For stroke, observationalstudies suggest a strong inverse
relationship between vitamin Dlevels and stroke risk, with
significant protective effectsobserved particularly above 30
(09:51):
ng per mL threshold.
For cancer, extensive studiesindicate that adequate vitamin D
can lower cancer risksignificantly.
Higher serum concentrationsaround 40 ng per mL or above
show promise in reducing theincidence of colorectal and
breast cancer by as much as20-30%.
For immune health, vitamin Dsupports immune system function,
(10:14):
reducing inflammation byinhibiting the action of T
helper cells 1 and 17, whichdrive inflammation in autoimmune
conditions and allergies.
Vitamin D potentially decreasessusceptibility to respiratory
infections, including COVID-19.
Higher vitamin D levelscorrelate with better infection
outcomes, reducedhospitalization rates and
decreased severity ofrespiratory illnesses.
(10:37):
For dementia and Alzheimer'sdisease, lower vitamin D levels
are linked with increased riskof dementia and cognitive
decline.
Studies suggest maintaininglevels above 30 nanograms per
milliliter could substantiallyreduce this risk.
For diabetes, vitamin D plays arole in glucose metabolism,
(10:57):
insulin sensitivity and may helpdelay the progression from
prediabetes to type 2 diabetes.
Achieving and maintainingvitamin D levels between 40 and
50 nanograms per milliliter maysignificantly cut diabetes risk.
Lastly, pregnancy and birthoutcomes.
Adequate vitamin D statusduring pregnancy lowers risk for
gestational diabetes,preeclampsia and preterm births.
(11:20):
Levels above 40 nanograms permilliliter are particularly
beneficial in significantlyreducing these risks.
Per the data that we're goingover.
Despite this data, most clinicaltrials, due to their flawed
designs, haven't capturedvitamin D's potential
effectively.
Participants often startedtrials already above the
(11:40):
protective threshold or receivedinsufficient doses, which
dilutes results.
In short, while randomizedclinical trials struggle to
demonstrate clear benefits dueto methodological issues,
observational and mechanisticstudies consistently indicate
substantial health benefits athigher vitamin D levels.
Given the robust body ofobservational and mechanistic
(12:00):
data, you might wonder whyguidelines from authoritative
bodies like the EndocrineSociety remain so conservative.
One primary reason is theirstrict reliance on randomized
controlled trials, or RCTs.
Rcts are considered the goldstandard in clinical evidence,
favored because theytheoretically remove bias and
clearly link interventions withoutcomes.
(12:21):
Unfortunately, as we discussedearlier, rcts designed for
pharmaceutical drugs are notwell-suited to study nutrients
like vitamin D.
This by itself could be its ownseries of episodes that we do
hear down the road.
Participants frequently starttrials with adequate baseline
vitamin D levels receive dosestoo low to make a difference, or
(12:43):
control groups are allowedadditional supplementation, all
of which dilute potentialeffects.
Another factor is what's knownas epistemic humility.
That's a cautious scientificstance recently emphasized by
the Endocrine Society in their2024 update.
Epistemic humility acknowledgesuncertainty in interpreting
existing evidence.
(13:03):
The Endocrine Society arguesthat without strong, consistent
results from multiple RCTs, thatendorsing widespread
supplementation at higher dosesmight be premature or even risky
, particularly given thehistorical tendency to overhype
nutritional interventions.
And they're not wrong there.
These guideline committeestraditionally focus on direct,
(13:25):
easily measurable outcomes likefractures, rather than broader
health markers such as immunefunction or long-term chronic
disease prevention.
Since many benefits from highervitamin D levels, like reduced
cancer or dementia risks,manifest slowly over years,
they're harder to confirmconclusively in very short-term
trials, like most RCTs.
(13:45):
Consequently, even thoughobservational studies,
biological mechanisms andmeta-analyses suggest
significant potential benefits,major health organizations
remain reluctant to increaserecommended vitamin D levels
until RCT evidence becomesundeniably clear.
This tension leaves us withconservative guidelines that may
fail to fully reflect thebroader health benefits that the
(14:08):
observational and mechanisticdata do strongly imply.
Not everyone accepts theEndocrine Society's conservative
stance.
Following their 2024 guidelines,dr Michael Holick, a prominent
and polarizing vitamin Dresearcher.
He helped identify how vitaminD is produced in the skin via
UVB radiation and advocated forits broader importance beyond
(14:30):
rickets, in areas like immunityand chronic disease.
He published a strongcounter-statement arguing that
these guidelines ignore evidencesupporting higher vitamin D
levels.
Hollick emphasized 20significant health outcomes that
improve, notably at vitamin Dconcentrations above specific
thresholds.
Above 60 nanograms permilliliter.
(14:50):
Reduced the risk ofpreeclampsia in some studies.
Above 50 nanograms permilliliter.
Reduced the risk ofpreeclampsia in some studies.
Above 50 nanograms permilliliter.
Reduced the progression frompre-diabetes to type 2 diabetes
and lowered breast cancerincidence.
Above 40 nanograms permilliliter.
Decreased risks of autoimmunedisorders, cesarean section
births, infant dental caries,digestive cancer relapses,
(15:11):
multiple sclerosis and prematurebirths.
At above 30 nanograms permilliliter.
Significant reductions incancer mortality, cardiovascular
mortality, colon cancer,covid-19 mortality, respiratory
distress syndrome, osteomalaciaand upper respiratory tract
infections.
The data that Hollis citedsuggests that 30 nanograms per
(15:33):
milliliter should represent abare minimum target for serum
vitamin D, with 40 nanograms permilliliter or higher being
optimal to ensure broaderprotection across multiple
health outcomes.
Hollis and other researchers'point was this by setting
thresholds too low, currentguidelines might inadvertently
overlook important achievablehealth benefits supported by a
(15:54):
growing body of research.
Given these complexities, thepractical question becomes how
do we safely and effectivelyachieve optimal vitamin D levels
?
Supplementation remains themost efficient and reliable
method for consistentlyincreasing serum vitamin D
concentrations.
Vitamin D supplementation witharound 2,000 IUs effectively
(16:14):
raises serum 25-hydroxy vitaminD above 30 nanograms per
milliliter in 90% of adults andcomfortably maintains these
levels in most people.
To achieve even higherprotective levels of 40 to 70
nanograms per milliliter, adaily dose between 4,000 and
6,000 IUs of vitamin D3 havebeen recommended.
(16:36):
But what about vitamin D fromsun exposure?
Sunlight naturally triggersvitamin D synthesis in the skin,
but effective and safe exposuredurations vary significantly
based on the season, locationand skin type.
Research conducted inSwitzerland illustrates this
clearly.
In spring and summer months,about 10 to 15 minutes of midday
sun exposure to approximately22% of uncovered skin, such as
(17:01):
arms, face and neck, is enoughto produce around 1,000 IUs of
vitamin D without significantlyincreasing risk of sunburn or
erythema.
However, during autumn andwinter, particularly at northern
latitudes, the requiredexposure can skyrocket to
several hours, often making itimpractical or unsafe due to
(17:21):
sunburn risk and coldertemperatures, while modest
exposure about 10-15 minutesdaily in warmer seasons can
substantially boost vitamin Dlevels safely.
Relying exclusively on sunlightis usually insufficient during
colder months or cloudy periods,making supplementation a
valuable tool.
But what about safety at highersupplement doses?
(17:43):
The official tolerable upperlimit for vitamin D intake is
set at 4,000 IUs a day,representing the highest daily
intake that is unlikely to poserisks of toxicity for most
adults intake that is unlikelyto pose risks of toxicity for
most adults.
Originally, the tolerable upperlimit was considered at 10,000
IUs a day, but was reduced dueto limited toxicity data from
case reports involving extremelyhigh doses, up to 40,000 IUs
(18:07):
per day, which can lead tocomplications such as elevated
calcium levels or kidney stones.
Vitamin D toxicity largelymanifests as calcium toxicity
because vitamin D increasescalcium uptake in the intestines
.
It's important to note thatmost data suggests signs of
calcium toxicity tend not tomanifest up until someone
reaches around 150 nanograms permilliliter, equivalent to 375
(18:31):
nanomoles per liter.
Within the body ofobservational data we looked at
today, the potential benefittapers off around 80 nanograms
per milliliter, equivalent to200 nanomoles per liter.
The recent rebuttal to theEndocrine Society suggests that
maintaining serum hydroxyvitamin D concentrations within
a protective range, ideallybetween 40 and 70 nanograms per
(18:53):
milliliter, using dailysupplementation of 2,000 to
6,000 IUs a day, combined withsensible, modest sun exposure in
summer months, is a balancedand safe approach supported by
the current evidence.
Is this range really desirablefor most people?
Well, I'll give you my opinion.
I agree with the datasupporting safety with vitamin D
(19:13):
levels between 40 and 70nanograms per milliliter,
assuming that people haveoptimal conutrient status of
things like vitamin K andmagnesium.
That being the case, it doesn'thurt most of us to be in that
range, and there is compelling,albeit controversial, evidence
that range may be optimal forreduced disease risk.
The bottom line guidelines willcontinue evolving, but your
(19:36):
health choices don't have toswing wildly with them.
Consider testing your vitamin Dlevels, discuss these targets
with your healthcare providerand ensure your approach to
vitamin D is informed, balancedand evidence-driven, because
ultimately, the goal isn't justto avoid deficiency, like is the
goal of current recommendations.
(19:56):
It's to achieve optimal health.
Thank you for tuning in to thisepisode of Daily Value.
Until next time, keepquestioning, stay informed and
always value your health.
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