LINUS
PAULINGINSTITUTE
OREGON STATE UNIVERSITYRESEARCH NEWSLETTERMARCH-MAY 2022

VITAMIN D, ZINC, AND COVID-19
COVID will likely be a global public healthconcern for years to come. Thankfully,
clinicians and researchers have developed
various public health protocols, vaccines,
and treatment options that reduce thelikelihood of serious illness and deathfrom COVID. In addition, we now haveemerging information about the rolethat micronutrients might play incomplementing these strategies.

VITAMIN D
Rationale: Although its role in immunity
is still a burgeoning area of research,vitamin D is known to have multiple effects
on the production, development, andregulation of immune cells. Vitamin D also
plays a role in cell barrier functions andthe production of antimicrobial peptides.

At the Linus Pauling Institute, we believethat this is important to share the current
state of the science to help you makeinformed decisions about your health.
Therefore, we continually monitor the latest
scientific evidence regarding micronutrientsand COVID.

Additionally, the immunomodulatory
properties of vitamin D can help control
an overactive immune system andreduce immune deficiencies. This makes
vitamin D important for diseases inwhich an overactive immune response
can result in sustained and undesirable
inflammation, such as COVID.

This article focuses on vitamin D and zinc,and future newsletters will highlight othermicronutrients.

Lastly, low blood vitamin D concentrations
increase the risk of contracting respiratory
tract infections.
Continued on page 4

IN THIS ISSUE
Vitamin D, Zinc, and
COVID-19.................1
From the Director.......2
Broccoli FAQ...............3
Diet and Optimum
Health Online: ...........6

FROM THE DIRECTOR
Photo credit: Hannah O’Leary

The new year at the Linus Pauling
Institute is off to a great start! At thetime of this writing, we have justcelebrated Linus Pauling Day, ourannual commemoration of the life andachievements of Dr. Linus Pauling.

Emily Ho, PhD
Endowed Chair and Director,
Linus Pauling Institute

Our Linus Pauling Day
webinar on vitamin C
can be viewed at:
lpi.pub/VitaminC2022

On February 28, 2022 – Dr. Linus
Pauling’s 121st birthday – the Institutehosted a webinar called Beyond theCommon Cold: Elucidating the Roles ofVitamin C in Health.
This online webinar featured Dr. Jeanne
Drisko (who joined us last year for
our Linus Pauling Day event) andDr. Qi Chen, both from the Universityof Kansas Medical Center. We planon bringing you highlights from thiswebinar in our next issue.
Our next webinar will be on dietary
indoles, cruciferous vegetables, andcancer, featuring over 30 years of
research at Oregon State University.
This will be presented by Dr. David E.
Williams, University Distinguished
Professor and the Linus Pauling
Institute Helen P. Rumbel Professor for
Cancer Prevention (see details below).

2

As always, we encourage you to registerfor the event even if you cannot attend
live – registered guests get first accessto the video recording and all otherwebinar materials.
Lastly, we have recently re-establishedthe Director’s Circle at the Linus Pauling
Institute. The Director’s Circle is agroup of trusted thought leaders who
have a vested interest in our future. Its
members primarily serve as an advisoryboard to me, and they also work as
advocates to promote the activities
and mission of the Institute within
their networks.
You will be hearing from our Director’s
Circle members in the near future. If you
are interested in learning more about thisgroup, please contact me. We are always
looking for more people to take an active
interest in the Institute.
As always, stay happy and healthy.
Talk to you again soon,

Emily Ho

BROCCOLI FAQIn December 2021, Dr. Emily Ho provided the last webinar of our 25th anniversary series, Cancer Fighter:
Harnessing the Power of Broccoli. The response to her webinar and broccoli sprout growing demonstration
was amazing, and we appreciate the enthusiastic feedback. Due to time constraints, we were unable toanswer all of your questions during the event. Therefore, in lieu of our normal “Reader Question” section,
we are summarizing common questions from the webinar with answers provided by Dr. Ho. Enjoy!

Why focus on broccoli or broccoli sprouts?

If I put broccoli sprouts in my smoothies,
will that work the same as chewing?

Broccoli is an abundant source of glucoraphanin, which
can be transformed into a molecule called sulforaphaneby the enzyme myrosinase, also present in broccoli.

Yes and no. While chopping up the broccoli sprouts
releases glucoraphanin and myrosinase, sulforaphane
is not very stable. It might react with some of the otheringredients of your smoothie or start to oxidize, making
it less effective.

Researchers believe that sulforaphane is a potent
anti-cancer molecule, as I talked about in the webinar.

Is it bad to cook broccoli?

If you are going to put broccoli sprouts into a smoothie,
be sure to drink it as soon as possible. You can also freezea purée of broccoli sprouts in small “shots” that can be
added to a smoothie just before you drink it. These will
thaw quickly, allowing you to drink them right away – wedo this in our clinical studies!

No, but just be aware that the myrosinase enzyme isdestroyed by heat. Light cooking is fine. Try steaming it
for 5 minutes. As long as there is some crunch left in thevegetable, you are probably getting some – if not most –of the sulforaphane you would get when eating theraw vegetable.

Are broccoli supplements a good alternative
to eating broccoli or sprouts?

Don’t worry too much if they are slightly overcooked.
All cruciferous vegetables have vitamins, minerals, andfiber that are not only resilient to cooking but also havebenefits against cancer. Getting some vegetables in any
way is good for your health.

They can be. One challenge is that you need active
myrosinase to get sulforaphane from these supplements.
Sometimes the enzyme is still active in the supplements,
but it’s hard to know for sure.

Do broccoli sprouts cause the same intestinalgas issues as eating cruciferous vegetables?

Our research trials have shown that supplements cannot
match sprouts in terms of sulforaphane production, even
if extra myrosinase is added. However, getting some isbetter than none – supplements are a good alternative if
you cannot tolerate eating broccoli or broccoli sprouts.

Unfortunately, they can. All cruciferous vegetables
contain a carbohydrate called raffinose that our bodies
can’t digest. If you have problems with intestinal gas
after eating sprouts, the best thing you can do is to eat
smaller servings.

Can we just eat the seeds instead of the sprouts?
Yes, but make sure to grind them up first. Otherwise,
the myrosinase and glucoraphanin might not come into
contact with each other. Be warned: they might not bevery tasty. Many commercial supplements use broccoli
seed as their source, rather than sprouts.

Over time, you may be able to eat more sprouts as thebacteria in your intestine adjust. You could take overthe-counter gas relief products to help in the meantime.
Thankfully, as I mentioned in the webinar, broccoli
sprouts have much higher amounts of glucoraphanin
per weight than the mature broccoli plant. Even if you
are eating small amounts of sprouts, you can still getsome of the cancer-fighting compounds.

How long do the seeds last?
Seeds from cruciferous vegetables last at least three
years but possibly as many as five. To extend their lifespan,
keep the seeds dry and cold. For our research studies,
we keep ours in the freezer – it’s the best way to preserve
their glucoraphanin content.

Can other seeds be used instead of broccoli?
Broccoli seeds have the most glucoraphanin content,
though kohlrabi seeds contain a moderate amount.
There is much less in the seeds of cabbage, kale,
Brussels sprouts, and other cruciferous vegetables.

Missed the webinar?
You can still catch it online at:
lpi.pub/BrocVsCancer
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Continued from cover

Vitamin D status
Vitamin D status isassessed by measuring
25-hydroxyvitamin Dlevels in the bloodstream.
Low vitamin D status
is defined as a bloodconcentration below
20 ng/mL. The thresholdfor deficiency is below
12 ng/mL. Studies vary on
which level was used tocategorize subjects withlow vitamin D status.

Vitamin D testing
Vitamin D blood tests are
standard laboratory tests
available from a medical
provider. There are also
over-the-counter tests that
can help you determine
your blood vitamin D
concentration.

COVID Data: Available evidence fromobservational studies confirms that low
vitamin D status is associated with anincreased risk of contracting COVID.
Additional evidence suggests that low
vitamin D status increases the risk ofsevere illness and death due to COVID.

Bottom Line: Of all the vitamins andminerals studied in the prevention andtreatment of COVID, vitamin D is the mostpromising. However, the lack of large
experimental studies makes specificrecommendations difficult.

A limitation of these studies is that blood
vitamin D concentrations were often
measured at inconsistent times, either
before or after people developed COVID.
This makes the relationship more of aninference rather than a direct connection.

In general, vitamin D supplements areuseful for correcting an existing deficiency.
This helps lower the risk of respiratory
tract infections – and this was true before
the pandemic. It is best to take daily
vitamin D supplements rather than taking
supplements once an infection is underway.

Ultimately, the data clearly indicatethat low vitamin D status should be
avoided both prior to and during a
COVID infection.

The Linus Pauling Institute recommends
that healthy adults take 2,000 IU (50 mcg)
of supplemental vitamin D daily. There arefew food sources of vitamin D.

Can vitamin D supplements help people
who have already contracted COVID?
The data on this topic are not very clear.

The goal is to maintain blood concentrationsof vitamin D at or above 30 ng/mL, so it
is a good idea to follow up with vitamin D
testing. If you do not reach vitamin D bloodconcentrations of 30 ng/mL with 2,000 IU
daily, you could consider taking additional
vitamin D supplements. Some individuals
need vitamin D in excess of this amount inorder to reach target blood concentrations,especially if their vitamin D status is low.

Observational studies can only suggestthat a dietary supplement will improve
clinical outcomes. There are only a few
small experimental studies designed totest the impact of vitamin D supplements
on COVID. These studies suggest thatvitamin D supplements reduce the rate of
intubation and the length of hospital stay in
COVID patients with no effect on mortality.
Four large randomized controlled trials
investigating vitamin D supplements areunderway in the US, Canada, Mexico, andthe UK. At the conclusion of these trials,
there should be a better understanding of
how the use of vitamin D supplements caninfluence COVID outcomes.

The tolerable upper intake level for adults
is set at 4,000 IU of vitamin D per day.
Yet, in healthy people, adverse effects oftaking vitamin D supplements are unlikely
at intake levels lower than 10,000 IU/day.
For optimal results, consult yourphysician to measure your blood
vitamin D concentration and discuss a
supplementation strategy, if needed.

TYPES OF CLINICAL STUDIES ON MICRONUTRIENTS AND COVID
Meta-Analyses or Systematic Reviews: These are analyses of multiple clinical studies on a topic, typicallyusing pre-defined criteria to evaluate study quality. Considered the highest quality evidence available, theseanalyses are often used to inform recommendations on health. At the moment, few analyses of this type
exist concerning vitamins and minerals in the treatment of COVID.
Experimental Studies: This is a type of clinical trial where researchers actively control study variables andintroduce an intervention such as supplementation. These studies are considered more valuable since they
can directly test causation. Randomized controlled trials are one example of an experimental study. We arestill awaiting the results from several larger trials that use micronutrients in the treatment of COVID.
Observational Studies: This is a type of study where researchers analyze available data obtained from agroup of people with limited control of study variables. As these studies only support associations, they are
considered the least powerful type of clinical research. Currently, observational studies make up the majorityof published clinical research on micronutrients and COVID.
4SOURCES OF ZINC
Oysters (6 medium): 25-50 mg
Beef (3 ounces): 5-9 mg
Turkey (3 ounces): 3 mg
Cashews (1 ounce): 1.6 mg
Chickpeas (½ cup): 1.2 mg
For more, see the Micronutrient
Information Center page on zinc:
lpi.pub/ZincSources

ZINC
Rationale: Zinc has multifold roles in the
immune system, including antioxidant,
anti-inflammatory, and anti-viral properties
important for a healthy immune response.
Like vitamin D, zinc has immunomodulatory
properties.
Zinc deficiency increases the risk ofdeveloping one or more deficits in the
immune system, such as poor productionof T-cells and B-cells. People with low zincstatus are also more likely to have higher
markers of inflammation in response to aviral infection.
COVID Data: There are only a few
observational studies on zinc and COVID
patients. They suggest that patients withsevere COVID are more likely to have lower
blood zinc concentrations than people withmild or moderate symptoms.
Observational studies have also associatedzinc supplementation with improved
recovery time in COVID patients, but
experimental studies have not reproduced
this result. In general, the evidence onzinc supplementation is very weak andnot particularly informative.
In COVID trials on zinc supplements,
people who took high amounts of zincreported more stomach aches, nausea, andheartburn in the treatment groups than in
the controls. These are known side effects
of excessive zinc consumption.
As with vitamin D, several randomized
controlled trials on zinc in the treatment of
COVID are ongoing.

Bottom Line: There is no evidence
to support taking zinc supplements
to prevent a COVID infection. Thereis also no good evidence to suggest
zinc supplements are effective in thetreatment of COVID. However, there
are few studies available using zinc
supplements alone.
The Linus Pauling Institute recommends
that men consume 11 mg of zinc per
day and women consume 8 mg of zinc
per day. Make sure to include zinc-richfoods in your diet (see examples above).
The tolerable upper intake level forzinc is set at 40 mg per day, so getting
too much zinc from food alone is rarely
a problem.
If you do not eat any zinc-rich foods,
you may need a supplement to meetyour needs. Try not to exceed 40 mg ofzinc per day.
While the use of zinc supplements indoses above 40 mg per day for a shortperiod of time (such as a few days) is
not a concern for health, zinc interfereswith copper absorption. Consuming
more than 40 mg of zinc every day forseveral weeks can result in low copperlevels in the body.
While taking zinc lozenges is shown
to be effective against common cold
symptoms, they have not yet been
properly evaluated in the treatmentof COVID.

5

Limitations of clinical
trials on zinc
Blood concentrations ofzinc are a poor indicator of
how much zinc a person
consumes, except in thecase of severe deficiency.
There is currently no goodmarker for inadequate zincstatus. This limitation may
prevent researchers fromdetecting associationsof zinc status and COVID
outcomes.

Zinc lozenges
For more about zinclozenges in the treatmentof the common cold,
see the Micronutrient
Information Center:
lpi.pub/ZincLozenge

For the list of scientificarticles reviewed here,
see: lpi.pub/COVIDrefs

DIET AND OPTIMUM HEALTH ONLINE:The Linus Pauling Institute’s Conference Goes VirtualWith the restrictions on gathering during the pandemic, the Linus Pauling Institute opted to holda series of virtual conference sessions instead of our in-person biennial conference in 2021.
This virtual conference, Diet and Optimum Health Online, hosted sessions focused on healthy aging,the microbiome, and immunity.
Below, we briefly summarize the conference sessions. A more in-depth summary and links to someof the recordings can be found at lpi.pub/DOH2021

Dietary Components and
Healthspan: Honoring the Workof Bruce Ames

During his career, Dr. Bruce Ames developed aconcept he called Triage Theory. This theory posits
that the body will ration vitamins, minerals, and othercompounds if the supply is low, prioritizing immediate
survival over long-term health. This accelerates thediseases of aging.

The first session of the conference was dedicated toextending the healthspan, a concept we introducedin our cover article in the Fall 2021 LPI ResearchNewsletter. The career of Dr. Bruce Ames was thetheme of the presentations. Dr. Ames has contributed
immensely to our understanding of the role of dietaryfactors in healthy aging.

According to this theory, replenishing the body withmicronutrients that are in short supply will combat the
aging process. In addition, other non-essential dietarycompounds could delay the deleterious effects ofaging and extend the healthspan.

Dr. Janet King focused her presentation on goodnutrition for older adults. Dr. King worked with Dr.
Ames on clinical trials with zinc, demonstrating how
low dietary zinc could lead to the accumulation of DNA
damage.

For more about Dr. Ames and his contributions tonutrition and aging, see lpi.pub/AmesVideo

DNA damage does not often have immediate effects
on the body. However, it can lead to serious long-term
consequences if uncorrected. Inadequate zinc intake
has been associated with an increased risk of cancer
and other chronic ailments. This is a good example of Dr.
Ames’ Triage Theory (see right).
Dr. José Ordovás spoke about understanding individual
nutrition needs. He introduced the concept of
personalized nutrition – a recognition that people are
unique, so nutrition recommendations for vitamins,
minerals, and other dietary factors should be tailoredto the individual.
Dr. James Kirkland gave an update on his trials withsenolytic compounds, including dietary factors likequercetin and fisetin. Senolytic compounds are thosethat can destroy senescent cells. More about cellularsenescence and senolytics can be found in the Fall 2021
LPI Research Newsletter.
Dr. Kirkland presented his work using senolytics totreat various age-related conditions, with a special
emphasis on new trials in diabetes. This approachechoes Dr. Ames’ work looking for dietary factors that
could be used to extend the healthspan.
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Diet and Optimal Health:
The Role of the Gut Microbiome

Dietary Factors for a Healthy
Immune System

The second session of Diet and Optimum Health Online
examined the influence of diet and dietary factors on thecomposition of our gut microbiome. This session not only
focused on dietary components that feed healthy gut
bacteria but also on the health benefits associated withmanipulating the types and amounts of microorganisms
living in our intestine.

The final session of the conference focused on therole that diet and supplements can play in combating
inflammation and infection. This session was timely, as
the information presented by the speakers touched on
ways that diet and dietary supplements may influence
COVID outcomes.
Dr. Adrian Martineau reviewed the current data on
vitamin D status and COVID. Dr. Martineau also spoke
about the ongoing trials relating vitamin D status to therisk of COVID infection and the immune response to
COVID immunization. He stressed that more informationon this topic will be published very soon.

Two presentations focused on the influence of fiber
on the composition of the gut microbiota. Dr. Hannah
Holscher began by speaking about the fibers in plants andthe types of bacteria that prefer to consume them. Since
certain bacterial families are linked to good health, it is
now possible to design interventions with specific foods
or fiber supplements to determine if they elicit the desired
health benefits.

Dr. Mette Berger spoke about the micronutrient statusof critical care patients. She noted that many people
admitted to the ICU often have a low blood concentrationof one or more vitamins and minerals. Extended
hospitalization often exacerbates these deficits, which
can be accelerated by increasing levels of inflammation.
Strategies designed to address micronutrient needs arelikely to improve outcomes in critical care patients.

Dr. Jens Walter reviewed the complex relationships
surrounding fiber supplements and changes to the gut
microbiome. In clinical trials, both fermentable and nonfermentable fiber supplements had beneficial properties.
The use of fermentable corn bran fiber supplements was
associated with improved insulin sensitivity, increased
satiety, and beneficial changes to the gut microbiome.
On the other hand, the use of non-fermentable cellulose
fiber supplements reduced inflammation despite theabsence of detectable changes to the gut microbiome.

Dr. Simin Meydani discussed the importance of
maintaining adequate micronutrient status in the elderly.
While good nutrition helps older individuals maintaina proper immune response, it is very commonly
overlooked. Dr. Meydani’s group has worked on several
studies using vitamin, mineral, and botanical supplements
to help reduce inflammation levels and lower the risk ofcontracting infections in older adult populations.

Dr. Leigh Frame’s presentation highlighted the
production of short-chain fatty acids by bacteria,
which can happen during the fermentation of fibers.
Small clinical trials show that short-chain fatty acids
have been associated with increased gut motility,
appetite regulation, and obesity prevention. However,larger experimental trials are needed to understandthe role of short-chain fatty acids in health.

Lastly, Dr. Philip Calder spoke about EPA and DHA –the omega-3 fatty acids most abundant in fish oil – andtheir role in blunting an overactive immune response.
He reviewed the data showing positive effects of DHA
supplementation on allergic responses, respiratory
illness, and arthritic pain. Dr. Calder also spoke about
DHA supplements’ potential to improve chronic pain
issues.

Dr. Fred Stevens spoke about the effect of gut bacteria
on bile acid metabolism and how this may lead to healthbenefits. In particular, he discussed his research on
xanthohumol and its influence on the gut microbiota –a topic that was covered in more detail in the Fall 2021
LPI Research Newsletter.

THE NEXT DIET AND OPTIMUM HEALTH CONFERENCE?
The next Diet and Optimum Health conference is tentatively scheduled for Fall 2023 at Oregon State
University in Corvallis, Oregon. Notifications will be sent to all previous conference attendees whendates have been finalized.
If you would like to be added to the notifications list, email us at lpi@oregonstate.edu

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

INSIDE: ARE VITAMIN D AND ZINC USEFUL IN THE FIGHT AGAINST COVID-19?

JOIN US FOR
DAM PROUD DAY!

April 27, 2022

Dam Proud Day is Oregon State
University’s annual day of giving.
The Linus Pauling Institute is raising
donations for the Simone and Balz
Frei Graduate Fellowship Fund insupport of young nutrition scientists.
Help make this day a success!

Want to know more?
See http://lpi.pub/DamProudfor more information or contact
Andrew.Norwood@osufoundation.org