LINUS
PAULINGINSTITUTE
OREGON STATE UNIVERSITYRESEARCH NEWSLETTERSPECIAL EDITION 2020

Nutrients for the immune system LOOK INSIDEACCESS GRANTEDFighting COVID-19 with Big Data
As US doctors fight COVID-19 throughout
the nation, an enormous amount of
useful data is being generated. Becauseof the emergent nature of this pandemic,
strategies to fight COVID-19 quickly evolve,
and valuable information from patient
records is scattered across the country.
How can researchers find patterns andclues for treatment options in such awidespread, disparate data stream?
Enter the National COVID CohortCollaborative, also known as the N3C.
The N3C is a nationwide collaborationof clinicians, informaticians, and otherbiomedical researchers. The collaborative
is tasked with two goals: collect COVID-19related health information into a centralized
data repository and create secure analytical
tools to process that data.

The N3C is spearheaded by Melissa
Haendel, PhD, principal investigator andDirector of Translational Data Scienceat the Linus Pauling Institute. To propel
this initiative, Dr. Haendel has brought
together more than 60 clinical centerswith the resources of the National
Institutes of Health.
Supported in part by Oregon State
University and the Oregon Clinical andTranslational Research Institute at Oregon
Health & Science University, the N3C willbuild, maintain, and regulate a new,secure database housing electronic
health records from COVID-19 patients.
Putting the nation’s health data together
into one place is not as easy as it sounds.
First of all, healthcare providers acrossthe country use different record systems
with no standard data format.
Continued on page 3

IN THIS ISSUE
AccessGranted..................1
From the Director....2
Flattening theCurve.....................2
Is IV Vitamin C
Effective Against
COVID-19?.............4
Nutritional Strategies
to Support theImmune System.......6

FROM THE DIRECTORThis special issue of the LPI ResearchNewsletter is focused on our ongoing
efforts surrounding the COVID-19pandemic. This issue features Dr.
Melissa Haendel’s work to help establish
a first-of-its-kind nationwide databaseof COVID-19 patient information (seefront cover). Also see our overview ofwhat we know about IV vitamin C use intreating COVID-19 (page 4).
Richard van Breemen, PhD
Endowed Chairand Director,
Linus Pauling Institute

References
van Breemen RB. Curr. Trends MassSpectrom. 18 (2020)
van Breemen et al. J. Agric. Food
Chem. 68 (2020) doi: 10.1021/acs.
jafc.0c01077

My research group is also joining
the effort against the pandemic.
We are using our patented affinity
selection technology to discovernatural compounds that can prevent
COVID-19. Our approach capitalizes on
the sensitivity, speed, and selectivity ofmass spectrometry to identify specificcompounds in complex mixtures(like botanical supplements) that caninteract with therapeutic targets, suchas viral proteins.
If our search is successful, we hope tobe able to use plant-derived products
in hand sanitizers, surface cleaningproducts, and even dietary supplements
to prevent the SARS-CoV-2 virus from
infecting human cells.

Despite the limitations that the global
pandemic has placed on our lives,
LPI researchers are still hard at work on
our usual research projects.
My group recently reported the resultsof a clinical trial on hops supplements.
We show that women using hops tocontrol menopausal hot flashes may
not have to worry about harmful druginteractions.
In addition, Dr. Adrian “Fritz” Gombart
recently published a highly cited review
addressing how supplements canmaintain a well-functioning immune
system (see page 6).
For references, see the sidebar or
the LPI website. More articles will be
published soon.
Thank you for reading this special
edition of our newsletter. You will behearing from us again very soon.
Please stay safe and healthy,

Richard B. van Breemen

FLATTENING
THE CURVE
Julie McMurry, MPH, is part ofDr. Melissa Haendel’s group at theLPI, has training in communicablediseases.
Early in this pandemic, McMurry
knew it was important to act
quickly and gather verifiable,accurate information on COVID-19.

This has now taken the form of awebsite: FlattentheCurve.com
More than just a collection ofscientifically accurate information,
it is a centralized hub for proven
COVID-19 strategies with a simple
message: You can do something tostop this pandemic.

2

There is more online than we cansummarize here, and the information
is updated frequently. Explore thewebsite to learn about COVID-19 andwhat you can do to help.
Julie McMurry, MPH, is an AssistantProfessor of Practice at OSU’s Collegeof Public Health and Human Sciences

Continued from front page“In the United States, there is no universal
system for our healthcare data,” explains
Haendel. “So you need to start byconverting data into a common system.
We have constructed a process forcollecting electronic health records frommany different institutions and storingthem in the same format.”
The N3C takes data from disparate systems
and standardizes them to a commonarchitecture. In a process Haendel refers to
as “harmonizing the data,” inconsistencies
across health data structures are eliminated.
In effect, this harmonization translates thedata from large hospitals and a variety ofsmall clinics into the same language. Data
consolidation opens up participation toa large variety of individual contributors,
allowing all to join this nationwide initiative.

“One of the most important
aspects of the N3C isthat the data sources
and methods are all fullyreproducible. This allows
greater transparency, invites
community review, andincreases the validity of theanalyses the N3C facilitates.”—Melissa Haendel, PhD
One advantage of this common framework
is to facilitate the use of computer-based
tools, such as machine learning and artificialintelligence. These types of analytical tools
can quickly sift through the data to answer
important questions.
“Machine learning algorithms can do things
like reveal candidate drugs that reduce theseverity of COVID-19 symptoms or build
predictive analytics in assisting clinical caredecisions,” Haendel explains.

Throughout this process, all theprotected health information of
COVID-19 patients remains safe. Only
the vital pieces of the data, such as theprogression of the disease or the effectof antivirals or other therapies, will beavailable to participating institutions withno risk of revealing patient identities.

For more informationon the N3C or how you
can request accessto data, go to:https://covid.cd2h.org

Data for the N3C will be gathered from asmuch of America’s diverse populations
as possible. This is more important thanit might sound. Since the United States iscomprised of people from many different
ethnic and socioeconomic backgrounds,
the N3C has the power to represent thehealth of many people from minority anddisadvantaged communities.
The more clinics and hospitals thatparticipate, the more it will be a resourcefor everyone in our country.
Several large hospitals are alreadyuploading data to the N3C, but moreclinical partners are always needed.
“It’s just unfortunate that it took a
global pandemic to spur us into action,”
Haendel continues, “This unique datasystem will be invaluable to researchersand clinicians.”
Ultimately, the N3C will be used to
predict patient responses to antiviral oranti-inflammatory therapies, identify
potential new treatments, and find otherclinical tests that can inform decision
making.
Because of its strong foundation, theN3C’s value against COVID-19 will growin the weeks and months to come.

3Clinicians whoare interested incontributing data or
participating in thissingular effort should
send an email to:data2health@gmail.com

IS INTRAVENOUS VITAMIN CEFFECTIVE AGAINST COVID-19?
A Review of the Theories and the Evidence
Every day, scientists
at the LPI answer yourquestions about theuse of IV vitamin C in
the treatment ofCOVID-19.
We provide somein-depth information
about this potential
therapy here, but asummary is also on
our website at:bit.ly/IV-VitaminC

Doctors on the front lines of the COVID-19
pandemic are using intravenous (IV)vitamin C (also known as ascorbic acid) tohelp people suffering from this disease.
As many LPI supporters know, IV vitamin C
therapy is nothing new. Drs. Linus Paulingand Ewan Cameron used it to treat cancer
patients nearly fifty years ago. Today, IV
vitamin C is used against cancer, sepsis,infections, and other conditions.
Vitamin C plays an important role in theimmune system (see pages 6-7), but IV
vitamin C can do things that oral vitamin C
supplements cannot.
To help you navigate this topic, we areproviding an evidence-based primer on IVvitamin C and how it might work against
serious infectious diseases like COVID-19.

Why use IV vitamin C?
Researchers and clinicians haveexperimented with IV vitamin C against
various forms of infectious disease andcancer for nearly a century. However,clinical data using this approach haveshown mixed results.
IV administration sends large doses ofvitamin C directly into the bloodstream,
bypassing the stomach and intestines.
This approach often results in blood
vitamin C levels in the millimolar (10-3moles/L) range. By comparison, blood
vitamin C levels only reach the highmicromolar (from 10-5 to 10-4 moles/L)
range after taking oral vitamin Csupplements.
In other words, after IV administration,
blood vitamin C levels are about 10 to 100
times higher than with supplements.
Such high concentrations allow IV
vitamin C to have unique effects in thebody. Since blood levels of vitamin C rise
immediately, it can be an important tool forclinicians to use in emergency situations.
4

How might IV vitamin C workin COVID-19?
Because there are limited peer-reviewed
data of IV vitamin C use against viral
infections, we must rely on results fromprevious trials of other inflammatory
conditions like sepsis.
Blood vitamin C levels in the millimolar
range may create superoxide and hydrogen
peroxide. In theory, these reactive oxygen
species can inactivate viruses and destroy
bacteria. While cells in our body havedefenses against these reactive molecules,
these pathogens do not.
Alternatively, IV vitamin C could dampen
the harmful effects of an overactive immune
system. A wave of inflammation and harmful
oxidative reactions precedes the respiratorycomplications seen in severe COVID-19
patients. Early intervention is very important.
Excess inflammation could lead to lower
vitamin C concentrations in the blood.
COVID-19 patients can also have low levels
of interferon, an antiviral cytokine. Could
IV vitamin C boost interferon production andallow the body to mount an effective defense
against the virus? It is one of many theories.

Blood Levels of Vitamin C
Blood Levels of Vitamin CBlood Concentrations
are Key
While vitamin C
supplements canprovide vital support
to the immune system,
oral supplementation
cannot match the bloodconcentrations reachedwith IV administration.

Intravenous
Intravenous
Vitamin
VitaminCC
Vitamin
VitaminCC
Supplements
Supplements

IV vitamin C should only be
used in a medical setting
by trained clinicians who
understand the safetyissues involved.

TimeTimeSince
SinceAdministration
Administration

How effective is IV vitamin C
in treating COVID-19?
We simply do not know. There are currently
no published data of IV vitamin C in thetreatment of COVID-19.
Despite the emergence of SARS and MERS
coronavirus outbreaks, no coronavirus
research has been done in humans usingvitamin C.
Without the guidance of clinical evidence,
it is difficult to determine the right timing
and dose of IV vitamin C. Case reports andfindings from clinical trials will fill thesegaps in knowledge.
At the time of this writing, IV vitamin C
is being tested in China, Italy, the UnitedStates, and other countries across theglobe.
We are hopeful that IV vitamin C will beshown to be effective. If so, this informationshould be quickly shared with front-line
doctors.
It is important to note that some medical
practices are advertising IV vitamin C as acure for COVID-19. No scientific evidence
supports this claim.

It is still important toregularly take supplements
and eat foods rich invitamin C. This will
maximize blood vitamin C
levels in the long term.

How safe is IV vitamin C?
IV infusions always require proper
administration by a medical professional.
Patients need to be screened to makesure it is safe for them. Some conditions,like a history of developing kidney stones,
might prevent a person from getting IVvitamin C.
From research on vitamin C and cancer,
we know that IV vitamin C is safe when
medical guidelines are followed.

Stay tuned
We are watching the clinical reports on
IV vitamin C and are in touch with theexperts on the topic. The Linus Pauling
Institute will share results of studies withIV vitamin C as soon as they become
available.
References
https://www.cancer.gov/about-cancer/treatment/
cam/hp/vitamin-c-pdq
Levine M, et al. Proc. Natl. Acad. Sci. 93 (1996)
doi: 10.1073/pnas.93.8.3704Marik PE. Pharmacol. Ther. 189 (2018)
doi: 10.1016/j.pharmthera.2018.04.007
Carr AC, Cook J. Front. Physiol. 23 (2018)
doi: 10.3389/fphys.2018.01182

5Paul Marik, MD isa physician who
developed an IV
vitamin C protocol
for critical sepsis
patients. In personalcommunications with
the LPI, Dr. Marik
reports that blood
vitamin C levels in some
COVID-19 patients arenearly undetectable,
making the case forIV vitamin C.
While Marik treats
severe COVID-19
patients with IVvitamin C, he always
uses it in combination
with drugs. This does
not support the soleuse of IV vitamin C inthese situations.

NUTRITIONAL STRATEGIES TOSUPPORT YOUR IMMUNE SYSTEMOver the age of 50?
Look for the following
in your multivitaminsupplement:•2 mg vitamin B6•

At least 100 µg ofvitamin B12•

10-15 mg of zinc•

Post-menopausal
women and allmen should look
for a multivitaminwithout iron.

There is always a good rationale to stay atpeak immune function. Beyond the current
COVID-19 pandemic, our immune systemdeals with perennial problems like theseasonal cycles of the common cold andinfluenza.
The immune system is extremely complex,
and its elaborate network of defense
mechanisms needs to work properly tobe effective.
An abundance of scientific evidence
supports the vital role that vitamins,minerals, and other nutrients play inmaintaining immune function.
Below is the LPI’s Immune System
Foundation: a list of nutrients that form
the base for a healthy immune system.
Often, these recommendations can bereached through a healthy diet and taking
a daily multivitamin.

On the next page are the Immune
Essentials: nutrients of vital importance tothe immune system when it is challenged.
Consider taking separate dietary
supplements for these specific nutrients.
As research about treating COVID-19 withdietary supplements evolves, we may update
this list with additional nutrients. At the timeof this writing, several phytochemicals arebeing evaluated for antiviral activity.
We will provide you with an update if andwhen that information becomes available.
References
Gombart AF, Pierre A, Maggini S. Nutrients 12 (2020)
doi: 10.3390/nu12010236
Childs CE, Calder PC, Miles EA. Nutrients 11 (2019)
doi: 10.3390/nu11081933
https://lpi.oregonstate.edu/mic/health-disease/immunity

The Immune System Foundation
The LPI recommendations are for adult men and adult women who are not pregnant or breast-feeding.
These recommendations are from food and dietary supplements combined.

Vitamin A

Vitamin B6

Vitamin E

DHA

Men: 900 µg/day

Men and Women:
1.3 mg/day

Men and Women:
15 mg/day

Eat oily fish
2 times per week

Vitamin B12

FolateCopperSelenium

Men and Women:
2.4 µg/day

Men and Women:
400 µg/day

Men and Women:
900 µg/day

Men and Women:
55 µg/day

Vitamin C

Vitamin DIronZincMen and Women:
400 mg/day

Men and Women:
2,000 IU/day

Men: 8 mg/day

Men: 11 mg/day

Women: 18 mg/day

Women: 8 mg/day(including beta carotene)

Women: 700 µg/day(See note below)

Special note:
Before menopause, women need 18 mg of iron per day. Following menopause, this recommendation decreases to 8 mg per day.

6

IMMUNE ESSENTIALS
Vitamin C, vitamin D, zinc, and DHA play a special role in immunity. While the usual LPI recommendations for thesenutrients can be attained by diet and a daily multivitamin, we recognize that your immune system might face additional
challenges at certain times. Dietary supplements are an important strategy to help you stay healthy.
Review the supplement information below and determine whether you should consider extra supplementation.
Be sure to note our cautions to avoid taking too much or harmful drug interactions.

Vitamin CZincCup to 2,000 mg
per day

Znup to 40 mg
per day

Immune functions:Vitamin C is an antioxidant that
protects cells against damaging free radicals
produced by the immune system. Vitamin C
also may increase the production and functionof certain immune cells.

Immune functions:
Zinc is required for the growthand development of immune cells. Zinc is a
structural component of proteins critical fornormal immune function. It is also important
for the synthesis of antibodies.

Why take a supplement?
Vitamin C can be depleted during a serious
illness or infection. Extra vitamin C might behelpful for older adults.

Why take a supplement?
Extra zinc might help if you feel a cold coming
on. Older adults are more susceptible to zinc
deficiency.

Caution:More than 2,000 mg of vitamin C a day mightcause intestinal gas, bloating, and diarrhea.
If you are prone to kidney stones, talk to
your doctor before starting any vitamin Csupplements.

Caution:Try not to exceed 40 mg of zinc a day from a
combination of diet and supplements.

Vitamin D

DHADDHA

250 mgper dayup to 4,000 IU
per day

Immune functions:Vitamin D increases theproduction of small peptides and proteinsthat can damage bacteria or viruses. It also
limits the amount of inflammation generated
by immune cells in an infection.

Immune functions:
Docosahexaenoic acid is anomega-3 fatty acid also known as DHA. It canbe converted into compounds that reduce
inflammatory damage caused by bacterial
and viral infections.

Why take a supplement?
Evidence suggests that a daily vitamin D
supplement protects against respiratory
infection. People who rarely go outside, areseverely overweight, wear sunblock, or havedark skin are more likely to have low blood
vitamin D levels without supplementation.

Why take a supplement?
If you are not eating oily fish 1-2 times per
week or taking a supplement, you are likely
not getting enough DHA.
Caution:If you are prone to bleeding or are on bloodthinners, consult your doctor before taking
DHA supplements. The only vegan source ofDHA supplements is from algae oil.

Caution:Vitamin D supplements should be taken
daily if possible. Do not take large amounts(greater than 10,000 IU) of vitamin D in asingle day unless advised by your doctor.

7

LINUS PAULING INSTITUTE
Alexander Michels, Newsletter Editor
Victoria Drake, Associate Editor
Sandra Uesugi, Assistant Editor
Cover Art by Julie McMurryOregon 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

LINUS PAULING INSTITUTE RESEARCH NEWSLETTERSPECIAL COVID-19 EDITIONFEATURING• A New Online Database of
COVID-19 Patient Data
• The Facts Surrounding
IV Vitamin C in Treating
COVID-19• Nutrients to Help Support
Your Immune System