LINUS
PAULINGINSTITUTE
OREGON STATE UNIVERSITYRESEARCH NEWSLETTERWINTER 2021

VITAMIN D AND COVID-19: What you need to know LOOK INSIDELIPOIC ACID SUPPLEMENTS
AND WEIGHT LOSS:

IN THIS ISSUE

A New Clinical Trial Sheds Light on Potential Benefits
Investigators at the Linus Pauling Institute, along with their collaborators at
Oregon Health & Science University, recently published results of a clinical trial
using lipoic acid supplements. This study shows that lipoic acid supplements canhelp some people lose weight.

For over 20 years, scientists and clinicians
have explored the potential health benefitsof lipoic acid, including its ability to promotehealthy aging and mitigate cardiovasculardisease.
Researchers at the Linus Pauling Institutehave found that lipoic acid reduces
oxidative stress, improves detoxification
mechanisms, and alters lipid metabolism inanimal models. Clinical trials at the Institutehave demonstrated the same effects andalso suggest that lipoic acid plays a rolein maintaining a normal circadian rhythm,
otherwise known as the body’s internal clock.

Lipoic Acid Supplements
and Weight Loss.........1
From the Director......2
In Memoriam.............2
Sponsor Highlight......3

What is lipoic acid?

LPI Students.............3

Lipoic acid is a naturally occurring
compound produced by both plants
and animals. It has a unique chemical
structure: it is a medium-chain fatty acidwith two sulfur atoms at one end (seeillustration on page 4).

Reader Question........3

Lipoic acid is typically found attached
to enzymes, where it acts as an electron
carrier. These enzymes are involved inenergy and amino acid metabolism in the
mitochondria.
Continued on page 4

Researcher Highlight..5
Immune Support.......6
Vitamin D and
COVID-19.................7

FROM THE DIRECTOR
Photo credit: Hannah O’Leary

This is an auspicious year for the Linus
Pauling Institute. This year marks the25th anniversary of the Institute coming
to Oregon State University. Also, on
February 28, 2021 we will celebrate the120th birthday of the late Dr. Linus Pauling.

Emily Ho, PhD
Endowed Chair and Director,
Linus Pauling InstituteOn December 9, 2020,
Dr. Emily Ho presented“Think Zinc! Fighting
Infection and Boosting
the Immune System.”
The video of this event isavailable at:
http://lpi.pub/ZincVideo

This year, we encourage everyone tochallenge their view of nutrition. To
achieve optimal health, we need to think
about the right time, right dose, and righttarget in your body – and that recipe
for health is likely going to be different
depending on your circumstances.
Dr. Pauling dreamed of going in thisdirection more than 50 years ago, calling
this concept “orthomolecular medicine.”
Science and technology are only now
catching up with his vision.
Earlier this year, the National Institutes of
Health announced a new strategic planthat has a specific focus on “Precision
Nutrition” – a recognition that therelationship between diet and diseaseis highly complex and individual.

I had the pleasure of joining leadersin the field to share and discuss this
topic with the NIH this January. Thereis a consensus that the one-size-fitsall approach to vitamins, minerals,
and other dietary factors needs to berevisited.
At the Institute, we know a highly
integrated and holistic approach isneeded to find out what foods anddietary supplements (and how much ofeach) will help achieve the best health.
I hope that this priority from the NIH
will help us to realize the promise of
Dr. Pauling’s legacy.
Expect more from me soon on our plansto take personalized nutrition into thenext era of the Institute. For now, I hope
you enjoy this issue.

Photo credit: Hannah O’Leary

IN MEMORIAM
It is with a heavy heart that we announce
the death of Melissa Quin McDougall,
who passed away suddenly on August23, 2020 in Chatsworth, California.
Melissa was a graduate student working
with Dr. Maret Traber at the Linus Pauling
Institute from 2011-2017.

Photo Credit: Hannah O’Leary

Melissa’s groundbreaking work at theInstitute revolved around the previously
uncharacterized effects of vitamin E
deficiency on embryonic development.
Using zebrafish as a model, shedemonstrated the initial consequencesof low vitamin E status in the developing
embryo, including dramatic effects on
survival and overall health.
In 2017, Melissa graduated with her PhD
in Molecular Nutrition from Oregon State
University and became a registereddietitian nutritionist (RDN). She went on
to complete postdoctoral work at Cornell
University. In 2019, she was hired by
Pharmavite as a nutrition scientist.
2

As a child, Melissa loved to swim. She
participated in synchronized swimmingand swam competitively through highschool. She loved the theater andhad roles in numerous high school
productions. Her passions were herfamily, learning, outdoor activities, andprotecting our environment.
Her colleagues at the Institute remember
Melissa as an extremely talented
scientist and a phenomenal scholar.
Melissa’s enthusiasm for her work was
exemplary. She will be missed by all who
had the pleasure of working with her.
In Melissa’s memory, her family asks thateveryone commits to learning something
new and to being a responsible stewardof our Earth’s resources. They also
ask that you please consider making acontribution to one of Melissa’s favorite
charities: Friends of The Earth; Action for
Healthy Kids, Inc.; Feeding America; or
your local food bank.

SPONSOR HIGHLIGHT
Dr. Donald Reed, a renowned scientist in antioxidant metabolism, was the first interim
director of the Linus Pauling Institute at Oregon State University in 1996, while theInstitute was moving from Palo Alto, California to Corvallis, Oregon. He has beena good friend of the Institute ever since.
In 2015, Dr. Reed established the Caron and Donald Reed Fellowship Fund.
Recognizing that students need extra support at the beginning and end of theirgraduate careers, Dr. Reed wishes to gift them independence from financial concerns.
As a researcher, he appreciates how his fellowship keeps research progressing as
students finish their degree requirements.
We are highlighting this important program to encourage others to also support thisinvaluable graduate fellowship. If supporting young scientists is your passion, pleasejoin Dr. Reed in contributing to this fellowship program at https://lpi.pub/ReedFellows“The first year in a graduate
student’s career is a very
important time. I want to givethem the time to learn about
the important research at the
Linus Pauling Institutewithout financial worries.”		

LPI STUDENTS
Recent Graduates
Three graduate students
from the Linus Pauling
Institute recently
defended their PhD
dissertations. We wish
them great success inthe years ahead.

Luying Chenvan Breemen laboratory—Donald Reed, PhD

READER QUESTION
webinar on zinc, Dr. Emily Ho said that phytate from seeds can
Q. Inbeher
a problem. I eat pumpkin seeds to get more zinc. What can I do to
reduce the effects of phytate?

Joseph Meeuwsen
Beckman laboratory							— From D.B. via email
found in nuts, seeds, grains, and legumes can bind minerals and
A. Phytates
reduce their absorption in your intestine. One way of reducing phytate
content in these foods is to soak them in water. However, most people don’t
want to eat soggy nuts or seeds, so you can dry or re-roast them afterward.
Sprouted foods also are a good source of zinc with minimal amountsof phytate.
Instead of doing the extra work, you could just add another serving of theseeds to your routine. Phytate does not prevent absorption of all zinc, just a
fraction of it. The more zinc sources you have in your diet, the less you need
to worry about phytate.
							— From Dr. Emily Ho

3

Daniel Nosal
van Breemen laboratory

Continued from coverYour body usually produces adequate
amounts of lipoic acid to meet yourmetabolic needs.
However, something different happens
when lipoic acid is taken as a supplement.
Often marketed as alpha-lipoic acid, themolecule is found in a free (not enzymebound) form. This allows it to take otheractions in the body, like stimulating certain
types of cell signaling.
Lipoic acid supplements have beenshown to stimulate glucose metabolism,
antioxidant defenses, and anti-inflammatory
responses. For these reasons, lipoic acidhas been investigated as a complementarytreatment for people with diabetes, heartdisease, and age-related cognitive decline.

Changing focus
Over the last few decades, a number ofclinical studies on lipoic acid have been
completed. However, some researchers– including the Linus Pauling Institute’s
resident expert on lipoic acid, Dr. Tory
Hagen (see highlight on page 5) – feel thatthese study designs left some room for
improvement.
Lipoic acid trials often focus on people whohave a disease diagnosis, such as diabetes.
However, the results of those trials are
difficult to extrapolate to the general
population.
In other words, previous studies do notdemonstrate that lipoic acid could help
people who do not have pre-existing
conditions.
Racemic mixtures
are 50:50
combinations of theR- and S- forms of amolecule. For lipoic
acid supplements,
the racemic mixture
is simply called“alpha lipoic acid.”
Supplements that
contain only the
R-form of lipoic acidwill be labeled
as such.

Another issue is the formulation of the
supplement. In many research studies,lipoic acid is provided as a racemic mixture
that contains two forms of the molecule.
This is also the most common form in themarketplace.
However, Dr. Hagen and others advocateusing only the R-form of lipoic acid because
it is the form that is found in nature. There issome evidence that the R-form of lipoic
acid is better absorbed, has fewer
gastrointestinal side effects, and may act
on target tissues better than the S-form of
the molecule.
On the other hand, the racemic mixture
is less expensive and more stable in a
supplement form.
4

New study, new revelations
Dr. Balz Frei, the former Director of theLinus Pauling Institute, led a team ofexperts that included Dr. Hagen to designand conduct a better clinical trial on lipoic
acid. Recently published in The Journal of
Nutrition, this study was a joint effort with
Oregon Health & Science University.
The study focused on people who were both
overweight and had high triglyceride levels
without a diagnosed disease. During thestudy, participants took either 600 mg of
R-lipoic acid or a matched placebo daily for
24 weeks.
The primary objective of the trial was tosee if lipoic acid supplementation could
reduce the amount of triglycerides in the
blood. In the end, that did not happen –blood triglyceride levels did not change
dramatically in either group.

The R-form of lipoic acid

However, many participants taking lipoic
acid supplements lost weight during thetrial. The lipoic acid group lost 1.7% of theirbody weight, as compared to the placebogroup that did not lose weight.
While that does not appear to be a dramaticweight loss, that number conceals some of
the remarkable weight loss seen in someof the study’s subgroups. For example, infemale study participants, a 9% reduction inbody fat was noted in the lipoic acid groupwhen compared to the placebo group.
The group taking lipoic acid supplements
experienced some other benefits. For
example, this group had lower urinary
F2-isoprostane levels, suggesting that they
were experiencing less oxidative stress.
The participants taking lipoic acid also had
lower levels of a protein biomarker called
ICAM1, suggesting lower inflammationlevels.

The future of lipoic acid
“Lipoic acid supplements can be beneficial,”
said Hagen, who served as a lead author on
the published study. “But like many dietary
supplements, it’s possible that thesebenefits will not be seen by everyone taking
them – it is not a perfect panacea.”“Not everyone in the lipoic acid group
showed weight loss during the trial,” added
Dr. Gerd Bobe, principal investigator at
the Linus Pauling Institute and one of
the study’s statisticians. “While this wasclearly an improvement over taking aplacebo, our study suggests that lipoic acidsupplementation has its limitations.”
The benefits of lipoic acid supplements docome with drawbacks. In the clinical trial,some of the participants reported frequent
heartburn or stomach aches. These
symptoms are not uncommon with lipoic
acid supplements, especially when taking
large doses on an empty stomach.

Cost can also be an issue. Lipoic acidsupplements, especially R-lipoic acidsupplements, can be quite expensive. It canbe a costly endeavor to find out that the
supplements do not work out for you.
“We need to continue our studies exploring
the mechanisms behind the benefits,”
concluded Hagen. “Otherwise we’ll neverknow why lipoic acid might work for somepeople and not others.”“Ultimately our goal is to create a moretargeted approach to lipoic acidsupplementation in the future.”
References
Bobe et al. J Nutr 150 (2020)
doi: 10.1093/jn/nxaa203
Keith et al. Biochem Biophys Res Commun 450 (2014)
doi: 10.1016/j.bbrc.2014.05.112
Keith et al. Pharmacol Res 66 (2012)
doi: 10.1016/j.phrs.2012.05.002

RESEARCHER HIGHLIGHTTORY M. HAGEN, PHD

For nearly three decades, Dr. Tory Hagenhas worked to understand how lipoic acidsupplements act in the body. His journeybegan under the mentorship of Dr. Bruce
Ames at the University of California,
Berkeley. Together, Drs. Hagen and Ames
started on the path to understand how andwhy we age with the hope of learning how
to live longer and feel better.

evidence for lipoic acid supplements inhealthy older adults.
As more research emerges, Dr. Hagen hopes
to see an increase in funding for trials focusedon older adults. Ultimately, he aims to discover
how lipoic acid and other dietary supplements
may aid our pursuit of healthy aging.

After joining to the Institute in 1998,
Dr. Hagen and his team consistently
demonstrated the benefits of lipoic acidsupplementation for older animals. From
maintaining cellular antioxidant levels tocell-signaling pathways, each study foundsimilar results: lipoic acid could make oldanimals appear like young animals, atleast biochemically.
In recent years, Dr. Hagen’s focus
has transitioned into human studies.
Although there are some clinical data
demonstrating the utility of lipoic acid in
the treatment of diabetes, there is little

5

The Hagen Lab groupin 2019: (L-R)
Dr. Kate Shay, Judy
Butler, Dr. Tory Hagen,Amanda Radke, and
Dr. Nicholas Thomas.
Photo Credit: Hannah O’LearyIMMUNE SUPPORT:
Can multivitamins help?
Why do older adults
face an increased
risk for micronutrient
deficiencies? See
the Micronutrient
Information Center for
more information:
http://lpi.pub/
OlderAdults

As we age, our risk for vitamin and mineral
deficiencies increases. While the immune
system is complicated, there is no doubtthat proper nutrition plays a key role in the
immune function.
Research suggests that more than onethird of older adults in the United States,
Canada, and Europe falls short of the dietaryrequirements for at least one micronutrient.
These shortfalls can have a big influence on
how the body responds to infections.
With this in mind, many have postulated
that taking a daily multivitamin supplement
might help support the immune system.
This may be a low-cost strategy to lower therisk of serious respiratory illness, especially
if the supplement contains micronutrientscritical to immune function like vitamin C,
vitamin D, and zinc.
Dr. Adrian Gombart at the Linus Pauling
Institute tested the efficacy of this idea in a
recent clinical trial, published last year in thejournal Nutrients.

Although a multivitamin,
the study supplement
did not contain all
micronutrients. Instead,
it only contained selectvitamins and minerals
for immune support,
including 10 mg of zinc,
400 IU of vitamin D, and
1,000 mg of vitamin C.

Utilizing an over-the-counter multivitaminsupplement marketed for immune support,
the trial involved 42 healthy older adults,
ages 55 to 75 years.
During the trial, study participants refrained
from consuming large amounts of zinc,vitamin D, and vitamin C from food andavoided taking any vitamin or mineral
supplements. Half of the study participants
took the multivitamin once per day, while
the other half received an inactive placebo.

Before and after the 12-week study, bloodand saliva were collected from participants
to examine nutrient levels and biomarkers
of immune status. Participants also
documented any illnesses that occurred
during the study.
Unsurprisingly, the researchers found thatblood concentrations of vitamin C and zincincreased in the multivitamin group and
not in the placebo group. The multivitamingroup also showed fewer symptoms of
illness, reported less severe illness, and had
shorter duration of illness when comparedto the placebo group.
“Although the study was limited toself-reported illness, the differences were
striking,” Dr. Gombart noted. “While asimilar number of participants from eachgroup reported symptoms, days of sickness
in the supplement group were effectively
cut in half.”
The research team also measured otherimmune system indicators to explain theseresults, but no differences were found.
Overall, this study is encouraging and atimely validation of Dr. Linus Pauling’s
message about micronutrients and theimmune system. He often advocated forfinding the optimal amounts of vitamin C
and other nutrients to support the immune
system.
Although Dr. Gombart cautions that his
study was relatively small, it provides
excellent groundwork for new andlarger clinical trials to explore the role ofmultivitamins in the immune system.
Bayer Consumer Care AG funded the study
through an Institution Initiated Research
grant and provided the supplements usedin the study. Bayer had no role in the study’s
design, execution, or data interpretation.
References
Fantacone et al. Nutrients 12 (2020)
doi: 10.3390/nu12082447
Calder et al. Nutrients 12 (2020)
doi: 10.3390/nu12041181
Gombart et al. Nutrients 12 (2020)
doi: 10.3390/nu12010236
Photo Credit: Hannah O’Leary

6

VITAMIN D AND COVID-19:
What you need to know

As the COVID-19 pandemic continues to spread acrossthe world, vitamin D deficiency has emerged as apossible factor in the disease. This is not surprising
as vitamin D plays an important role in maintaininga healthy immune system. Vitamin D will likely gain
more attention as the winter progresses, a time when
respiratory infections are common and vitamin D levels
can be low.
At the Linus Pauling Institute, we have been reviewing theavailable evidence on vitamin D and COVID-19 since thepandemic began. As your source of scientifically accurate
information on vitamin D and health, below we present a
brief evaluation of the research studies on vitamin D and
COVID-19 to help guide you through the pandemic.

What is missing from this information?

How do we know vitamin D is important in
COVID-19?

Since vaccines rely on a healthy immune response, lowvitamin D levels could reduce the effectiveness of a
vaccination. We do not yet know if there are any effects ofvitamin D levels on mRNA vaccine’s efficacy, specifically.

Before the pandemic, we knew that people with low
blood concentrations of vitamin D had an increased
risk of severe respiratory infection. The current studies
simply reinforce that relationship: people hospitalized for
COVID-19 also tend to have low blood concentrations ofvitamin D.

Although vitamin D supplements are of interest intreating COVID-19, there is still very little evidence thattaking vitamin D supplements after you get sick will bebeneficial. Getting an appropriate amount of vitamin D
prior to an infection seems the best course of action.

Vitamin D deficiency appears to also be associated withincreased COVID-19 severity, evidenced by advanced
progression to pneumonia, increased need for ventilatory
support, and a higher mortality risk.

Currently, there are some clinical trials focused on
vitamin D as a COVID-19 treatment, but those data will
not be available for many more months.

Who is at risk for vitamin D deficiency?

The takeaway

Blood vitamin D concentrations are lower in people wholive in higher latitudes, have dark skin, do not spend timeout in the sun (or often wear sunblock), are overweight,
or simply do not consume enough through their diet.
Older adults can also have poor vitamin D status because
they do not synthesize it efficiently.

Vitamin D is an important factor that influences theimmune response. The COVID-19 pandemic has only
underscored this relationship. Since vitamin D status isassociated with disease severity, it is more important
than ever to keep your vitamin D levels above 30 ng/mL.
To check your vitamin D levels, blood testing can be done
through your physician. However, in the midst of thispublic health crisis, it is not always feasible to travel to aclinic or hospital to get your blood drawn. Other options
for getting blood vitamin D levels checked include
at-home blood tests or mobile blood draw services.

Many experts agree that blood vitamin D concentrations
above 30 ng/mL are preferred. People who take regularvitamin D supplements are more likely to have blood
vitamin D levels above this threshold, even if they fall into
one of the risk groups above.

Will high vitamin D levels prevent
COVID-19?

In the absence of testing, you still avoid vitamin D
deficiency. The Linus Pauling Institute recommends
that all adults take 2,000 IU (50 μg) of supplemental
vitamin D each day. Daily doses up to 4,000 IU (100 μg)
of supplemental vitamin D are generally considered safe
for adults.

No. Vitamin D is not a shield against viruses – it is only
one of many factors that impact your immune response.
In our review of the literature, we noted that there werestill people diagnosed with COVID-19 even though
their blood levels of vitamin D were above 30 ng/mL or
regularly took vitamin D supplements.

For detailed information about the published studies
on vitamin D and COVID-19, see the Micronutrient
Information Center at: http://lpi.pub/vitDCOVID-19
7

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

MULTIVITAMINS:IMPORTANT SUPPORTFOR YOURIMMUNE SYSTEM?

INSIDE: THE RESULTS OF THE LINUS PAULING INSTITUTE’S LATEST CLINICAL TRIAL