LINUS
PAULINGINSTITUTE
OREGON STATE UNIVERSITYRESEARCH NEWSLETTERSEPTEMBER-NOVEMBER
2022

VITAMIN D SUPPLEMENTS ON TRIAL:
Are They “Useless”?

Earlier this summer, two studies on vitamin D caused a bit of a stir,inciting some media reports that proclaimed vitamin D supplements are“useless” for supporting bone and immune health. Here, we discuss theimportant findings from these vitamin D trials and provide some context
and perspective.
In short, there is no reason to stop taking your vitamin D supplements.
Vitamin D is a fat-soluble, hormone-likemolecule that plays an important role inhealth. Yet, many people in the world today
are not getting enough vitamin D, especiallyin high northern or southern latitudes
during the winter.
The primary source of vitamin D is sunlight
exposure, as dietary sources are scarce.
Because of the risk of skin damage andcancer from sunlight, many people turn tovitamin D supplements to meet their needs.
But questions have been raised about
the need for vitamin D supplements andtheir role in maintaining health after theresults of clinical trials reported no clearbenefit in the people taking them.

Two recently published studies onvitamin D supplements – one on bonehealth and the other on immunity – havefurther fueled that argument. This has
prompted recent editorials and media
reports questioning the overall usefulnessof vitamin D supplements.
As is often the case, this presents only
one side of the story. At the Linus Pauling
Institute, we believe that it is importantto understand the designs of theseclinical trials for a proper perspective on
the conclusions. As we discuss below,
neither study warrants a change to the LinusPauling Institute’s recommendations onvitamin D supplements.
Continued on page 3

IN THIS ISSUE
Vitamin D Supplementson Trial...................1
From the Director.....2
The Drug-Nutrient
Interactions App.......2
Vitamin C andSepsis......................5

FROM THE DIRECTOR
Now more than ever before in our
nation’s history, health needs to be
our highest priority.
Photo credit: Hannah O’Leary

It seems hard to imagine, but right now
60% of all adults in the United States
have a chronic health problem – andthis is only going to get worse. A wave ofolder adults is entering our healthcaresystem. In the next decade, one in five
adults will be over the age of 65.
Emily Ho, PhD
Endowed Chair and Director,
Linus Pauling InstituteAnd while some will meet their later
years with resilience, many will not.
This is what we call an “aging tsunami”
because its impact will overwhelm ourhealthcare system – that is, if we donothing. The time to act is now.
Since the world is desperately in needof a paradigm shift, the Linus Pauling
Institute will lead a new approach.
Instead of us being reactive, let us start
being proactive and change the face ofhealth in this country – and the world.
On October 14, 2022, Oregon State
University launched its second capitalfundraising campaign. For thiscampaign, the Linus Pauling Institutewill focus on moving the needle towardachieving optimal health. We know that
this goal is within our reach – and you
can help us achieve it.

INTRODUCING THE DRUG-NUTRIENTINTERACTIONS APP
Some dietary supplements can interfere with the action of drugs, andsome drugs can influence how certain nutrients act in the body. It is
incredibly important for physicians and consumers alike to be aware ofpotential interactions.
This is where the Institute’s Drug-Nutrient Interactions (DNI) app plays
an important role in healthcare. Developed from information in theMicronutrient Information Center and funded by a grant from Pfizer, Inc.,
this app is freely available for both Android and iOS devices.
The DNI app was developed to be a quick and easy reference forphysicians, yet is simple enough for anyone to use. The app focuses onclinically relevant drug-nutrient interactions.

2In the upcoming months and years, youwill be hearing more about our futureplans to redefine healthcare. As we closein on our goals, you will also have newopportunities to engage with us and help
shape the Institute’s future.
My desire is to develop the tools youneed to take charge of your health, so
you can live better longer. At Oregon
State University, we have the means to
not only affect the nation but the entire
world. I hope that you will join the Linus
Pauling Institute in looking for innovative
solutions to promote and optimize yourhealth and vitality.
Please enjoy the first edition of ouronline-only newsletter. In this issue,
we review the current state of nutrition
research. The next issue will come inthe late fall and provide more in-depth
updates from our research programs.
Talk to you again in December,Continued from cover

The VITAL Study:
Vitamin D and Bone Fractures
In July 2022, the results of arandomized, placebo-controlled trial
on vitamin D and bone fractures werepublished in The New England Journalof Medicine. These were new findings
about the VITAL cohort – a group of
approximately 26,000 older adults (50years and older) from the Boston area.
In this recent paper, the authors lookedat two groups: those that were given
2,000 IU of supplemental vitamin D totake daily and those that were givena placebo. Using surveys and medical
records, the authors monitored theincidence of bone fracture in eachparticipant. After five years, the data
showed no difference in fracture risk
between the two study groups – theplacebo and vitamin D supplement
groups had equal chances of breaking
a bone.
Thus, the authors concluded thatvitamin D supplements were ineffective
in reducing fracture risk in thispopulation.

Looking deeper into
the dataThe results of the VITAL trial werestraightforward and logical: people
taking vitamin D supplements did not
see a reduction in bone fracture risk.
Given what we know about vitamin Dand bone health and the population
studied, was this to be expected?
To explain further, let us describe thestudy in more detail.
The VITAL study recorded bone
fractures, not bone mineral density.
While fracture risk is related to bonemineral density, bone strength isinfluenced by physical activity andgenetics.

Clearly, vitamin D cannot influence
all of the factors that determine
fracture risk. It is only one of the many
components affecting bone mineraldensity. This makes bone fracture risk alimited parameter when evaluating theimpact of vitamin D supplements.
And, participants in the VITAL cohort
experienced below-average rates ofbone fracture. The incidence of fracturein this group was about 1.1% per year,
which is approximately four times lower
than the average for similarly aged
adults in the United States. A low rateof bone fracture makes it very difficult
to detect the effect of any intervention,including vitamin D supplementation.
Why was the bone fracture risk solow? One reason might be that many
participants in VITAL had higher than
average levels of vitamin D before
the study even started. In boththe control and treatment groups,
average baseline blood vitamin D
concentrations were approximately 30
ng/mL. For context, the Linus Pauling
Institute recommends achieving bloodconcentrations of 30 ng/mL or higher
for optimal health.
Blood vitamin D levels were high insome of the study participants because
they were allowed to take a daily
supplement containing up to 800 IUof vitamin D if they desired. So while
the placebo was given a supplement
without vitamin D added, about 40%of the study participants continued totake vitamin D anyway.
Put plainly, VITAL was not designed toproperly evaluate the effects of vitamin
D on bone health or the effects ofvitamin D supplements in those withlow vitamin D status. Therefore, thisreport does not provide any evidence
against the continued use of vitamin D
supplements.

Fracture risk is also influenced by how
likely you are to sustain a potentialbone-breaking injury, such as from afall or motor vehicle accident.

Continued on page 4

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Vitamin D has a strong
relationship to bonemineral density throughits actions on calcium.
Yet, bone mineral density
can be influenced by 12
different vitamins andminerals.
See the Micronutrient
Information Center onbone health for more:
lpi.pub/BoneHealthPrevious studies on bonehealth have shown thatbone mineral density
appears to be negatively
affected when blood
vitamin D levels are below
20 ng/mL.

Another report on
the VITAL cohort waspublished earlier in 2022.
Interestingly, the use ofvitamin D supplements
was associated witha 22% lower risk ofdeveloping autoimmune
diseases.

Continued from Page 3

The CORONAVIT Study:
Vitamin D and Immune Function
In September 2022, a clinical trial on
COVID-19 and vitamin D was published in
the research journal, The BMJ. This was apublication on the CORONAVIT cohort, agroup of 6,200 participants ages 16 and older
in the UK. This six-month trial examined
whether vitamin D supplementation affected
the risk of developing COVID-19 and otheracute respiratory tract infections.
The CORONAVIT researchers randomly
distributed the study participants into threegroups. Two of the groups were designatedas “vitamin D supplement groups.” Whether
or not participants in these groups actually
received these supplements depended on
their initial vitamin D blood concentrations.
Only participants with blood vitamin D levels
below 30 ng/mL (considered suboptimalvitamin D status) received either the 800
IU or 3,200 IU vitamin D supplement,
depending on what group they wereassigned. Those who had blood vitamin D
concentrations above 30 ng/mL received
no supplements, although they were still
considered part of their assigned group.
The third group of participants wasconsidered a control group. They were notgiven any supplements, nor was blood
vitamin D measured at the start of the study.
At the end of the study, blood vitamin D
concentrations were measured in randomly
selected participants from all study groups.
To determine if the use of vitamin D
supplements had influenced the immune
response, the authors periodically sent out
questionnaires to all participants to see ifthey had gone to the doctor for a respiratory
tract infection or had tested positive for
COVID-19.
The final analysis showed equal numbers of
respiratory tract infections in each group,
whether the participants were assigned to avitamin D supplement group or not. There
was also no difference in the number oflaboratory-confirmed COVID-19 cases
among groups.

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Looking deeper into
the dataSo, does the CORONAVIT trial suggestthat vitamin D supplements are ineffectivein the fight against respiratory tract
infections? Not entirely. The unusualdesign of the CORONAVIT study makes it
difficult to draw a solid connection
between vitamin D status and infection
risk.
The major concern was the treatment of
the control group. This group was notprovided any vitamin D supplements, butalso not provided a placebo – so theseparticipants were aware they were notgetting vitamin D. As a consequence,about 50% of participants in the control
group started taking vitamin D
supplements despite being asked not to
do so. Participants in the vitamin D
supplementation groups, however, hadlittle trouble following instructions.
Because blood vitamin D levels were notdetermined in the control group at thebeginning of the study, we have noinformation on their initial vitamin D
status. It is possible that these people hada lower risk of infection because they had
sufficient vitamin D already.
At the end of the study, only 300
people in the control group (out ofapproximately 3,500) had theirvitamin D blood concentrations
measured. The likelihood that theseparticipants were the ones who actuallycontracted a respiratory tract infection ispretty small.
And, in the groups provided with vitamin D
supplements, supplementation was only
partially effective. Approximately 40% ofstudy participants in the 800 IU per day
group and 15% in the 3,200 IU per day
group did not reach the target of
30 ng/mL by the end of the study,
potentially leaving these individuals
vulnerable to infection.
Because of these design issues, theCORONAVIT trial revealed very little
information of consequence about the useof vitamin D supplements in respiratory
tract infections and COVID-19.

Bottom Line
Although the two studies discussed inthis issue focus on vitamin D supplements,
the response to their findings distractfrom the important messages about thisvitamin. Establishing and maintaining
adequate vitamin D status is vital tohealth, regardless if vitamin D comesfrom a supplement or some other source.
Many people can reach optimum vitaminD status easily with dietary supplements.
But, this is not the only option available:
diet and sunlight are alternatives.
Regardless of the route
you choose, it is important to get yourblood vitamin D concentrations checked
periodically.
While there are benefits associated withblood vitamin D levels at 30 ng/mL orabove, vitamin D supplementation in
individuals who already have vitamin Dlevels above 20 ng/mL may only result insubtle health benefits that require
well-designed clinical trials to measure.
Ultimately, vitamin D is important forbone integrity and immune function, andvitamin D supplements continue to havetheir place for many people seeking tomaintain good health.
References
LeBoff et al. N Engl J Med 387 (2022);
doi: 10.1056/NEJMoa2202106
Jolliffe et al. The BMJ 378 (2022);
doi: 10.1136/bmj-2022-071230

VITAMIN C AND SEPSIS:The End of the Story?

In June 2022, findings from the LOVIT study appear toshow that intravenous vitamin C increases mortality insepsis patients. Does this signal the end of IV vitamin C
as a therapy for sepsis?
The LOVIT study is a randomized, placebo-controlled trialthat investigated the impact of vitamin C in the treatmentof sepsis. In this study, researchers enrolled participants
with sepsis and provided standard sepsis treatments plus IV
saline or IV vitamin C every six hours for four days. Responseto the treatment was monitored, and treatments wereevaluated over time.
At the end of the study, the authors found that IV vitamin C
did not help sepsis patients. In fact, after 28 days, the groupthat received IV vitamin C had a 20% higher risk of deaththan the group that received the placebo.
Although there are many clinical trials that have tried IV
vitamin C in the treatment of sepsis, few have suggested thatvitamin C provides a benefit to sepsis patients. Combination
therapy of IV vitamin C, thiamin, and hydrocortisone has
not yielded any significant benefit to sepsis patients despite
initial enthusiasm about this approach.
The LOVIT trial is the only trial to suggest that IV vitamin C
harms sepsis patients. When we consider the mortality datafrom all of the trials on sepsis conducted to date, it does notappear that IV vitamin C causes harm.
Is there a path forward for IV vitamin C as a sepsis therapy?
Earlier this year, a study from Korea suggested that IV
vitamin C should be administered for at least five days toprovide a significant benefit to sepsis patients. Since many
randomized clinical trials only provided IV vitamin C for up tofour days, extending the treatment period is one avenue toexplore in future studies.

References
Lamontagne et al. N Engl J Med 386 (2022); doi: 10.1056/NEJMoa2200644
Jung et al. Crit Care 26 (2022); doi: 10.1186/s13054-021-03872-3

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LINUS PAULING INSTITUTERESEARCH NEWSLETTER
Alexander Michels, Newsletter Editor
Victoria J. Drake, Associate Editor
Sandra Uesugi, Assistant Editor
Oregon State University
307 Linus Pauling Science Center
Corvallis, Oregon 97331
phone: 541-737-5075
fax: 541-737-5077
email: lpi@oregonstate.edu
website: lpi.oregonstate.edu