Meta-Analyses Confirm Vitamin D Defends Against COVID
September 19, 2022 Puzzle Piece
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his a direct copy of Analysis by Dr. Joseph Mercola
STORY AT-A-GLANCE
· Since December
2021, four large systematic meta-analyses have been published, looking
at either vitamin D levels, supplementation or both. In all cases, the
data consistently show that low vitamin D levels raise your risk of
COVID while higher baseline levels and/or supplementation lowers all
risks by 1.5 to three times.
· In the first of
these four meta-analyses, the odds of developing COVID-19 among those
with deficient or insufficient vitamin D levels were 1.46 times higher
than those with sufficient vitamin D. Their risk of severe disease was
also 1.9 times higher, and their risk of death 2.07 times higher.
· In the second
study, the odds of ICU admission based on vitamin D status were 2.63
times higher among those with severe vitamin D deficiency, 2.16 times
higher among those with deficiency, and 2.83 times higher among those
with insufficient levels. Mortality was also much higher in all patients
with low levels.
· In the third
analysis, only 12.19% of COVID patients who received vitamin D required
ICU admission, compared to 26.27% of those who did not get vitamin D.
· The fourth and
most recent analysis found “significant associations of vitamin D
supplementation with COVID-19, encompassing risks of disease worsening
and mortality,” especially in seasons characterized by vitamin D
deficiency and in patients with mild to moderate infection.
At this point, there is simply no question that vitamin D optimization
is a crucial component of COVID-19 prevention and treatment. In addition
to the many studies published during 2020 and 2021, since December
2021, four large systematic meta-analyses have been published, looking
at either vitamin D levels, supplementation or both.
In all cases, the data consistently show that low vitamin D levels
raises your risk of COVID while higher baseline levels and/or
supplementation lowers all risks by 1.5 to three times.
Therapeutic Role of Vitamin D in COVID
In the first of these four meta-analyses, “Prognostic and Therapeutic
Role of Vitamin D in COVID-19: Systematic Review and Meta-Analysis,”
published December 11, 2021, the researchers sought to determine “the
association between vitamin D deficiency/insufficiency and
susceptibility to COVID-19, its severity, mortality and role of vitamin D
in its treatment.”
A total of 72 observational studies, covering 1,976,099 patients, met
the criteria for inclusion. Compared to those with sufficient vitamin D,
the odds of developing COVID-19 among those with deficient or
insufficient vitamin D levels were 1.46 times higher.
Their risk of severe disease was also 1.9 times higher, and their risk
of death 2.07 times higher. One potential drawback was that all studies
ranked “high” for risk of bias. The studies also differed in their
definitions of severe illness and vitamin D deficiency/insufficiency,
making absolute comparisons difficult. That said, the authors concluded:
“Multiple observational studies involving nearly two million adults
suggest vitamin D deficiency/insufficiency increases susceptibility to
COVID-19 and severe COVID-19, although with a high risk of bias and
heterogeneity. Association with mortality was less robust.”
Vitamin D Status and Clinical Outcomes
In the second study, “Vitamin D Status and SARS-CoV-2 Infection and
COVID-19 Clinical Outcomes,” published December 22, 2021, the
researchers assessed “whether vitamin D status is associated with the
COVID-19 severity, defined as ARDS requiring admission to intensive care
unit (ICU) or mortality (primary endpoints) and with the susceptibility
to SARS-CoV-2 and COVID-19-related hospitalization (secondary
endpoints).”
Here, they included 54 observational studies (1,403,715 patients) that
measured the association between vitamin D status and risk of COVID
infection, hospitalization, ICU admission and death during
hospitalization. The measures for vitamin D status were as follows:
· Insufficiency — less than 75 nmol/L (30 ng/mL)
· Deficiency — less than 50 nmol/L (20 ng/mL)
· Severe deficiency — less than 25 nmol/L (10 ng/mL)
Seventeen studies reported the association between vitamin D status and
SARS-CoV-2 infection; nine reported the association with COVID-19
related hospitalization, 27 reported COVID-19-related ICU admission, and
35 reported COVID-19 related mortality. In summary, the odds of ICU
admission based on vitamin D status were as follows:
· Severe deficiency — 2.63 times higher
· Deficiency — 2.16 times higher
· Insufficiency — 2.83 times higher
Those with severe deficiency were also 1.68 times more likely to test
positive; those with deficiency were 1.83 times more likely to test
positive; and those with insufficiency were 1.49 times more likely to
test positive. In conclusion, the authors stated:
“Patients with low vitamin D levels present an increased risk of
ARDS requiring admission to intensive care unit (ICU) or mortality due
to SARS-CoV-2 infection and a higher susceptibility to SARS-CoV-2
infection and related hospitalization.”
The Effect of Vitamin D Supplementation
The third study, “The Effect of Vitamin D Supplementation on Mortality
and Intensive Care Unit Admission of COVID-19 Patients. A Systematic
Review, Meta-Analysis and Meta-Regression,” was published in May 2022.
The effect of vitamin D supplementation was found to be quite
significant — 12.19% of patients who received vitamin D required ICU
admission, compared to 26.27% of those who did not get vitamin D.
Six studies, involving 860 patients, had data on ICU admission. Of those
860 patients, 369 received vitamin D supplementation and 491 did not,
and the effect of vitamin D supplementation was found to be quite
significant — 12.19% of patients who received vitamin D required ICU
admission, compared to 26.27% of those who did not get vitamin D.
The data in all six studies strongly favored vitamin D. The ideal dose,
however, remains uncertain, as no linear relationship between dose and
odds ratio of ICU admission was observed.
Vitamin D and SARS-CoV-2 Infection, Severity and Mortality
The fourth and most recent study, “Vitamin D and SARS-CoV-2 Infection,
Severity and Mortality: A Systematic Review and Meta-Analysis,” was
published July 6, 2022, in PLOS ONE.
Here, they looked at COVID-19 in relation both to baseline vitamin D
status and supplementation. Thirty-eight studies — including two
randomized controlled trials — were included that had risk estimates for
at least one endpoint (risk of infection, severity and/or mortality).
In all, data on vitamin D status was available for 205,565 patients and
2,022 who were given vitamin D supplementation. According to the
authors:
“Random effects models showed that supplementation was associated
with a significant lower risk of both COVID-19 severe disease (SRR 0.38,
95% CI 0.20-0.72, 6 studies) and mortality (SRR 0.35, 95% CI 0.17-0.70,
8 studies).
There were no statistically significant dose differences between
studies: summary estimates with regular doses remain statistically
significant, suggesting that higher doses are not necessary. For
patients on vitamin D supplementation, a greater reduction in mortality
risk emerged in older individuals and at higher latitudes.
Regarding the quality of studies, assessed using the New
Castle-Ottawa quality scale, the analysis revealed in most cases no
statistically significant differences between low, medium or high
quality studies.
We found significant associations of vitamin D supplementation with
COVID-19, encompassing risks of disease worsening and mortality,
especially in seasons characterized by 25OHD deficiency and with not
severe patients.”
Why Randomized Controlled Trials Are Not Required
As noted by in a Twitter thread by Karl Pfleger, Ph.D., the data clearly
show vitamin D is strongly correlated with all COVID-19 risks, and we
do not actually need randomized controlled trials to draw this
conclusion:
“Most underlying studies are observational, but at the very least
knowledge of whether someone supplements D or of their D status is
strongly predictive of their COVID risks/outcomes. As I've noted
previously, RCTs are not required for this conclusion to be sound &
unquestionable. This establishes a risk factor & most other well
known COVID risks factors are also based entirely on observational data.
The data showing age, above-normal-weight, & comorbidities are
significant risk factors is also based entirely on correlation. No RCTs
establish these as risk factors but no one questions that they are. VDD
[vitamin D deficiency] should be thought of as another comorbidity, just
like diabetes.”
Indeed, at this point, the importance of vitamin D in the fight against
COVID ought to be common knowledge everywhere, especially in health care
circles. Yet the surgeon general of Florida, Joseph Ladapo, is the only
public health official who is actually recommending vitamin D
optimization for COVID.
This is crazy, as the effects of vitamin D were evident very early on in
the pandemic. I launched an information campaign about vitamin D back
in June 2020, which included the release of a downloadable scientific
report that detailed the science behind vitamin D. This report, as well
as a two-minute COVID risk quiz is available on StopCovidCold.com.
In December 2020, more than 100 doctors, scientists, Ph.D.’s and leading
authorities from 33 countries also signed an open letter12 to
the governments and health officials of the world, calling for the use
of vitamin D against COVID. Since then, the list of signatories has
grown to 220.
The letter recommended taking enough vitamin D to achieve a blood level
of at least 30 ng/mL (75 nmol/L), urged testing of all hospitalized
COVID-19 patients and adding vitamin D to the treatment protocol for any
patient whose level was below 30 ng/mL.
Not only did health agencies roundly ignore this sound advice, but they
also publicly tried to discredit the notion that vitamin D could have
any benefit at all, and attacked anyone sharing the good news about
vitamin D.
As just one example, in the summer of 2020, the Center for Science in
the Public Interest (CSPI), a self-proclaimed consumer advocacy group
bankrolled by the Rockefeller Foundation, among others, launched a
campaign against Mercola.com. The CSPI falsely accused me of
“profiteering from the pandemic” by selling nutritional supplements,
including vitamin D, while sharing scientific truth about its benefits.
The campaign culminated in a warning letter from the U.S. Food and Drug
Administration, in which they warned me to stop talking about vitamin D.
I reviewed this censorship attempt in “Why Is Info on COVID and Vitamin D Deficiency Suppressed?”
The fact of the matter is, data show vitamin D supplementation lowers
your risk of a positive test, speeds viral clearance, slows the spread
of infection, and lowers your risk of severe infection, hospitalization
and death, as summarized in “Vitamin D Deficiency and COVID-19 Severity” and many other articles.
Mechanisms Behind Vitamin D
At the end of October 2020, I published my own vitamin D review13 in
the peer-reviewed journal Nutrients, co-written with William Grant,
Ph.D., and Dr. Carol Wagner, both of whom are part of the
GrassrootsHealth expert vitamin D panel. You can read the paper for free on the journal's website.
As noted in that paper, dark skin color, increased age, preexisting
chronic conditions and vitamin D deficiency are all features of severe
COVID disease and, of these, vitamin D deficiency is the only factor
that is readily and easily modifiable.
You may be able to reverse chronic disease, but that typically takes
time. Optimizing your vitamin D, on the other hand, can be achieved in
just a few weeks, thereby significantly lowering your risk of severe
COVID-19.
In our paper, we review several of the mechanisms by which vitamin D can
reduce your risk of COVID-19 and other respiratory infections,
including but not limited to the following:
· Reducing the survival and replication of viruses15 and inflammatory cytokine production.
· Maintaining
endothelial integrity — Endothelial dysfunction contributes to vascular
inflammation and impaired blood clotting, two hallmarks of severe
COVID-19.
· Increasing
angiotensin-converting enzyme 2 (ACE2) concentrations, which prevents
the virus from entering cells via the ACE2 receptor — ACE2 is
downregulated by SARS-CoV-2 infection, and by increasing ACE2, you also
avoid excessive accumulation of angiotensin II, a peptide hormone known
to increase the severity of COVID-19.
Vitamin D is also an important component of COVID-19 prevention and treatment for the fact that it:
· Boosts your
overall immune function by modulating your innate and adaptive immune
responses and reduces respiratory distress and improves overall lung
function.
· Regulates inflammatory cytokine production, which is one of the lethal hallmarks of COVID-19.
· Helps produce
surfactants in your lungs that aid in fluid clearance and lowers your
risk of comorbidities, including obesity, Type 2 diabetes, high blood
pressure and heart disease.
Data from 14 observational studies — summarized in Table 1 of our paper —
suggest that vitamin D blood levels are inversely correlated with the
incidence and/or severity of COVID-19 and, importantly, that the
evidence currently available generally satisfies Hill's criteria for
causality in a biological system.
Why Sun Exposure Is the Best Way to Optimize Vitamin D
The ideal way to optimize your vitamin D level is by exposing large
portions of bare skin to the sun. I take an hour-long walk during solar
noon every day, wearing just shorts and a baseball cap, and have not
needed oral vitamin D supplementation for over 13 years.
This is not some theoretical obsession I have. I am now beyond convinced
that swallowing vitamin D is exponentially inferior to getting it from
the sun. I would encourage you to do everything in your power to get it
from the sun. And, when you get it from the sun, you should not be
swallowing it.
It is important to regularly check your vitamin D levels to see how you
are doing with your program. Ideally, your level should be between 60
ng/mL and 80 ng/mL. Last week my vitamin D level was 100, the first time
ever in my life I was in the triple digits, and all with no oral
supplementation for over a dozen years. Remember, vitamin D is a
biomarker for all the good things the sun does for you.
I believe this is largely because I was diligent this year to time the
middle of my daily walk around solar noon. Since I live in FL, which
practices daylight savings time, solar noon, is 1 PM. So I typically
start my walk around 12:30 and finish around 70-90 minutes later. Last
year I went out 1-2 hours earlier and my levels were only around 70, so
you can see the importance of timing.
Sun exposure also provides other biological health benefits over and
beyond vitamin D production. If the science of sun exposure interests
you, check out Dr. Roger Seheult’s MedCram lecture above. In it, he
explains the ins and outs of how sunlight impacts your health. One
really important health benefit you can only get from sunlight and not
oral supplementation is mitochondrial melatonin production.
The best review of the sun’s effect on melatonin is the February 2020
paper, “Melatonin in Mitochondria: Mitigating Clear and Present
Dangers,” published in the Physiology journal. It’s written by the best
researcher in melatonin, Russel Reiter, Ph.D.
Reiter’s key finding is that 95% of the melatonin your body produces is
made inside your mitochondria in response to near-infrared (IR)
radiation from the sun or other near IR sources. Only 5% of melatonin is
produced in your pineal gland.
Melatonin is a master hormone, a potent antioxidant and
antioxidant recycler, and a master regulator of inflammation and cell
death. These functions are part of what makes melatonin such an
important anticancer molecule.
So, to produce melatonin inside your mitochondria actually makes perfect
sense, as your mitochondria desperately need protection from the damage
caused by oxidative stress produced in the electron transport chain.
In summary, your mitochondria produce ATP, the energy currency of your
cells. A byproduct of this ATP production is reactive oxidative species
(ROS), which are responsible for oxidative stress. Excessive amounts of
ROS will damage your mitochondria, contributing to suboptimal health,
inflammation and chronic health conditions such as diabetes, obesity and
thrombosis (blood clots).
The good news is your body has a built-in way to counteract these ROS.
Inside your mitochondria, you also have an antioxidant system, and the
main antioxidant is melatonin.
Melatonin also upregulates your glutathione pathway, which is another
potent antioxidant pathway shown to play an important role in COVID.
Like vitamin D, glutathione deficiency is associated with COVID severity.
In short, your body is well-designed to address oxidative stress, but
you need sun exposure in order for that mechanism to work.
One aspect of sun exposure that Seheult did not mention was that it will
also increase your testosterone levels naturally. Most people aren’t
aware that the highest hormone concentration in men and women is
testosterone. Obviously levels are far lower in women, but testosterone
is higher than estrogen in women and it is important for optimal
biological function — just one more reason why you want to aim for daily
sun exposure on as much skin as possible.
Also remember it is not the sun that is the primary cause of sunburn and
skin cancer: It is elevated linoleic acid (LA) in the seeds, nuts and
seed oils you consume. LA should only be 1% to 2% of daily calories, and
it is over 20% in most people. It takes years to lower your LA levels
as it stays in your body for about seven years, so start eliminating it
from your diet today.
Guidance for Oral Vitamin D Supplementation
If you do opt for oral supplementation, as an absolute last resort,
there are additional considerations to take into account. For example,
you need 244% more oral vitamin D if you’re not also taking magnesium
and vitamin K2, so these three should ideally be taken together. You can
learn more about this in “Magnesium and K2 Optimize Your Vitamin D Supplementation.”
Remember, the most crucial factor when it comes to vitamin D is your
blood level, not the dose, as the dose you need is dependent on several
individual factors, including your baseline blood level. The level to
shoot for is between 60 ng/mL and 80 ng/mL (150 nmol/L to 200 nmol/L);
40 ng/mL should be considered the low-end cutoff.
Before you start oral supplementation, you’ll want to get a baseline
measurement. One of the easiest and most cost-effective ways of
measuring your vitamin D level is to participate in the GrassrootsHealth’s personalized nutrition project, which includes a vitamin D testing kit.
Once you know what your blood level is, you can assess the dose needed
to maintain or improve your level. The chart below can be helpful. Be
sure to remeasure your vitamin D level in three to six months, to
evaluate how your sun exposure and/or supplement dose is working for
you, and adjust accordingly.
Consider DAK1K2 for Vitamin D
Yours in Health and Wellness,
John W Brimhall, DC, FIAMA, DIBAK, Formulator
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