LINUS
PAULINGINSTITUTE
DIGITAL DIGEST

WINTER/SPRING 2024

LOOKING BACK AT DIET AND OPTIMUM HEALTH 2023 SEE INSIDEAGING WELL & OPTIMUM HEALTH
Exploring the Research on Micronutrients and Healthy Aging

On December 13, 2023, Dr. Emily Ho presented the webinar Aging Well & Optimum
Health: The Role of Micronutrients. She highlighted the Institute’s approachto healthy aging and the scientific data that inform the Institute’s vitamin andmineral recommendations. A synopsis of that presentation follows, including abrief discussion of the micronutrient studies that Dr. Ho reviewed.
Audience members had many more questions than Dr. Ho could answer in the
one-hour webinar. Answers to select audience questions can be found on page 5.
A recording of the presentation and Q&A session is available on our YouTube
channel.

A Role for Micronutrients in Older Adults
It’s no secret that vitamins and minerals are essential for health. If you are severely
deficient in any one of these micronutrients, you run the risk of immediate and serious
health consequences. Nowadays, however, severe deficiencies are usually avoidable
and rare in the United States.
More common are the subtle shortfalls. This is where people do not reach therecommended amounts of certain vitamins or minerals but have no obvious or
immediate health problems. At the Institute, we believe that a lifetime of more subtle
micronutrient inadequacies leads to poor health in the long term and drive thedevelopment of age-related diseases.
Reaching optimum vitamin and mineral status provides long-term benefits for healthand vitality. We refer to this as increasing our healthspan – living longer, better lives.
Continued on page 4

IN THIS ISSUE
Aging Well &Optimum Health.....1
From the Director....2
Micronutrient
Information Center
Updates...................3
Aging Well Q&A
Follow-Up................5
Precision Health:
Living Better,
Longer...................6

FROM THE DIRECTOR
I hope that your year is off to a great
start!

Photo credit: Karl Maasdam

At the Institute, the start of a new year
means hosting Linus Pauling Day. Thisis our annual celebration of the Linus
Pauling legacy that we hold each year
on Dr. Pauling’s birthday, February 28.
Part of this event included an open
house at the Linus Pauling Science
Center in Corvallis, Oregon.

Emily Ho, PhD
Endowed Chair and Director,
Linus Pauling InstituteWe also held our first webinar of theyear on Linus Pauling Day, hosting Dr.
Francesco Visioli from the University of
Padua in Italy. In his presentation, hespoke about the foods, micronutrients,
and phytochemicals that make up theMediterranean diet and the sciencebehind their health benefits.
Dr. Visioli is a long-time friend of theInstitute, having spent a couple ofsummers here in Oregon working
with several LPI investigators, theirstudents, and our staff. During his
recent acceptance speech for theFederation of European Nutrition
Societies Award (a very high honor!),he called his time at the LPI one of thebest experiences of his life.

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You can access the recording of Dr.
Visioli’s webinar Living Better, Longer:
Healthy Compounds Found in a
Mediterranean Diet on YouTube at thelink below. We will have more of the Q&Afrom this webinar in the next issue of theDigital Digest.
Please note that our annual day ofgiving, known as Dam Proud Day, isfast approaching. We can use your help
to support our Healthy Aging Research
Fund. We are also seeking support for
our flagship outreach program, theMicronutrient Information Center. See
more about Dam Proud Day on the backcover.
Part of this initiative involves apartnership with OSU’s Division of
Research and Innovation to support
student research fellows within theInstitute. Stay tuned to learn how you canhelp these students in the next issue ofthe LPI Research Newsletter.
Hope you enjoy this issue. As always,
thank you so much for your support!

MICRONUTRIENT INFORMATIONCENTER UPDATESFolate Article Updates•

Folate and Homocysteine: A high blood level of homocysteine is a risk factor forseveral types of cardiovascular disease. Of the vitamins involved in homocysteine
metabolism, folate status appears to have the greatest impact. Recent studies
suggest that folic acid supplementation, along with vitamin B6 and vitamin B12, may
help prevent stroke, especially in those with existing cardiovascular disease.

The full text of the article
on folate can be found at:
lpi.pub/MIC-folate
Information about highhomocysteine levels canbe found at:
lpi.pub/MIC-HCys

High blood levels of homocysteine are also a risk factor for cognitive decline,
dementia, and Alzheimer’s disease. There is limited evidence that folic acidsupplementation improves cognitive function, although more randomized
controlled trials are needed. It is nevertheless prudent to ensure adequate intakesof folate and other B vitamins throughout life for overall health.
•

Supplemental Forms: Folic acid is the most common form of folate supplement.
Many years of clinical trial evidence show that folic acid supplementation
supports healthy folate status in the body. Other forms of folate are available assupplements. However, despite claims by manufacturers, there is very little clinicalevidence that they are superior to folic acid.

Vitamin B12 Article Updates••

Vitamin B12 Status: Although measuring blood concentrations of vitamin B12(cobalamin) alone is useful, other blood markers may better describe vitamin
B12 status. Elevated blood concentration of methylmalonic acid is the specificindicator of vitamin B12 deficiency, but blood concentrations of total cobalamin,
holo-transcobalamin (also called “active vitamin B12”), and homocysteine can also
be used. Since there is no “gold standard” blood test, the manifestation of clinicalsymptoms is important in the diagnosis of vitamin B12 deficiency.
Who Might Need Supplements: Anyone who avoids animal products, such asvegans and vegetarians, is at high risk for vitamin B12 deficiency. While fortified foods(e.g., cereals, nutritional yeast) may be a source of the vitamin, it is generally advisedthat vegans and vegetarians take vitamin B12 supplements.
Additionally, older adults are at increased risk for vitamin B12 deficiency due totypically undetected inflammation in the stomach lining and the resulting decreasein stomach acid production. The use of antacids or other drugs that lower stomachacid also can reduce the absorption of vitamin B12 from food. The use of metformin,
which is most commonly prescribed to treat diabetes, can also reduce vitamin B12
absorption. Because low vitamin B12 status is common among older adults, theInstitute recommends that all older adults get 100 to 400 μg of vitamin B12 per day
from supplements.

•

Supplemental Forms: Cyanocobalamin is the main form of supplemental
vitamin B12 available in the US. Hydroxycobalamin is a form of vitamin B12
commonly used in Europe. Other forms of vitamin B12 include methylcobalamin andadenosylcobalamin.
Sublingual vitamin B12 (placed under the tongue until dissolved) is also available overthe counter in the United States. A few studies suggest that the use of sublingual
cyanocobalamin or methylcobalamin are effective at increasing vitamin B12 status.

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The full text of the article
on vitamin B12 can befound at:
lpi.pub/MIC-B12

Continued from Cover

While the Institute focuses on ways toextend healthspan with good nutrition, we
recognize that current science cannot yet
define optimum levels of micronutrientsfor each person. However, the Institutecontinues to conduct nutrition trials inboth animals and people towards thiseffort.
Dr. Ho selected a few of those trials tosummarize in her presentation. The
first was a preclinical trial conducted byher research group, showing how zincstatus influences inflammation in older
mice. Older animals that consumed adiet low in zinc had much higher levels
of inflammatory biomarkers than young
mice that consumed the same diet.
However, older mice that received a dietsupplemented with zinc fared muchbetter: inflammatory markers decreased,
and other aspects of the immune system
improved. This suggests that these older
animals had an undetected need formore zinc, which may also be present inolder people.

A summary of Dr.
Gombart’s study
can be found in theWinter 2021 editionof the LPI ResearchNewsletter.
A more detailed
overview of Dr.
Hagen’s study canbe found in the Fall
2023 edition of
the LPI ResearchNewsletter.

Recent clinical trials have also madeprogress toward a better understanding of
how multivitamins support the nutritional
status of older adults. Dr. Ho discussed two
studies led by investigators at the Institute,Drs. Adrian Gombart and Tory Hagen.
Dr. Gombart’s trial focused on immune
function in men and women over theage of 55. Half of the study participants
took an immune-focused multivitaminsupplement that was high in vitamin C,
while the other half took a placebo control.
At the end of the 12-week study, theindividuals taking the multivitamin showed
increased blood levels of vitamin C andzinc compared to those in the control
group. Although both groups reported
having respiratory illnesses throughout
the study, participants in the multivitamingroup reported less severe illness andshorter duration of illness when comparedto the control group.
These results suggest that immune
response was somehow improved bysupplementation, although determining
the specific mechanism requires further
investigation.

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Dr. Hagen’s trial focused on metabolism
in older men, primarily over the age of
70. Like Dr. Gombart’s study, half thestudy participants took a multivitaminsupplement every day, while the other half
took a placebo control. The supplement
was a multivitamin designed for older men,containing most vitamins and minerals andsome phytochemicals.
At the end of the six-month study,
participants in the multivitamin group
showed significant increases in blood levelsof several vitamins, especially vitamin B6,
vitamin D, and vitamin E.
Interestingly, a decline in cellular oxygen
consumption was observed in white blood
cells obtained from individuals in theplacebo group, which was not seen in themultivitamin group. This suggests that the
supplement protected the multivitamingroup from the decreases in mitochondrial
function that occurred in the placebo group.
Dr. Ho expressed that these studies are justthe beginning of our research that will help
us understand the roles of micronutrients inhealthy aging.
References:
Wong et al. J Nutr. 139 (2009);
doi: 10.3945/jn.109.106021
Fantacone et al. Nutrients 12 (2020);
doi: 10.3390/nu12082447
Michels et al. Nutrients 15 (2023);
doi: 10.3390/nu15122691

AGING WELL Q&A FOLLOW-UP

More Audience Questions Answered From Dr. Ho’s Webinar
NHANES data show that many adults don’t
meet potassium intake recommendations.
Why is this the case?

In the trials using multivitamins, the data forblood serum or plasma were shown. Were thecellular levels of the nutrients also tested?

Put simply, 80% of children, teens, and adults in
the United States are not eating enough fruit andvegetables every day. For example, adults average
only 1½ servings of vegetables and only 1 servingof fruit each day, which is far below the goal of 5-7
servings of fruit and vegetables every day.

For most vitamins and minerals, no. This is because
in most cases, the plasma levels are considered to be
the best indicator of vitamin status. The exception is
folate because red blood cell levels of that vitamin are
considered a more useful marker of folate status.
An analysis of red blood cell mineral status could bedone if additional funding is made available. In theory,
micronutrients can also be measured in white blood
cells, but these cells can be difficult to obtain in sufficientquantities for testing.

Most Americans need to dramatically increase fruitand vegetable intake in order to reach potassium
intake recommendations of 2,600 mg/day for
women and 3,400 mg/day for men. While fruit andvegetables are the primary sources of potassium inthe diet, some dairy products like yogurt and seafood
are also good sources.

In all of the reviewed studies, it was noted thatblood levels of many minerals are not very
helpful for assessing nutrient status. Why isthat?

Using dietary supplements to meet your potassium
needs is not recommended for several reasons,
including the risk of serious side effects.

Our bodies regulate blood levels of minerals to avoid
imbalances that could impact bodily functions. Whenblood levels increase, our body either stores the extra
minerals in tissues or eliminates any excess in urine.
When blood levels fall, our body accesses those extra
minerals from our tissues and limits urinary excretion
to keep blood levels steady. Typically doctors use bloodlevels of minerals as an indicator of organ function, notnutritional status.

Dr. Ho indicated that taking too much zinc
can interfere with copper absorption. If
we decide to take a zinc supplement, is it
important to also take a copper supplement?
Taking too much zinc can indeed interfere withcopper absorption, but this only occurs when copperand zinc are present in the digestive system at thesame time. If you take a zinc supplement, you canstill absorb copper from food if you do not take thezinc supplement with copper-rich food sources, suchas shellfish, seeds, nuts, and mushrooms. A copper
supplement is not necessary.

For example, if our body senses that it is not getting
enough calcium from the diet, it will take calcium
from our bone stores and also limit calcium loss in theurine. During that process, blood calcium levels remain
within the normal range, but calcium stores are slowly
depleting. Only when the calcium stores are nearlyexhausted do blood levels start to drop.

Adults should limit their zinc intake to 40 mg per day
to avoid these issues. Make sure to account for theamount of zinc you are getting from both food andsupplements.

Are there any home tests that we can use tomeasure our vitamin and mineral levels?

Where can we find the Institute’s
recommendations for vitamins andminerals?

Although many companies claim that they canaccurately assess your vitamin and mineral levels
through at-home tests, the scientific evidence supporting
their use is lacking.

The Institute’s Micronutrient Information Centeris the best source for this information. Intake
recommendations can be found in articles on
specific vitamins or minerals and in articles that
focus on specific life stages (older adulthood,pregnancy, and childhood).

The best tests still require a medical or research lab.
Speak to your healthcare provider if you are interested in
micronutrient testing.

In addition, you can check out the Micronutrients for
Health handout on our website.
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PRECISION HEALTH: LIVING BETTER, LONGER
The 2023 Diet and Optimum Health Conference
The Linus Pauling Institute’s biennial conference washeld on September 19 and 20, 2023 in Corvallis, Oregon.
This scientific meeting focused on the theme of precision
health and explored the latest advances that exist at theconvergence of personalized nutrition and healthspanresearch.
The conference covered a wide spectrum of nutrition
research, including the emerging role of data science, newbiomarkers for health, and interventions that promotehealthy aging.
Below is an overview of the keynote panel sessions thatbegan each day of the meeting.

Precision Nutrition Keynote Panel
Speakers: Cindy Davis (USDA), Holly Nicastro (NIH), andAndrea Wong (CRN)

Dr. Holly Nicastro, Coordinator for the Nutrition
for Precision Health Program at the National
Institutes of Health, provides an overview of the
All of Us research program.

This panel fostered a discussion on measuring individualized
nutritional needs. All of the panel members agreed that thisis a much-needed approach to advance nutrition science,as general dietary recommendations often fall short. Each
speaker brought different perspectives on an individualized
approach to nutrition and encouraged the use of different
tools, technologies, and techniques.
Dr. Holly Nicastro spoke about the All of Us research
program from the National Institutes of Health (NIH). The
goal of this program is to nurture long-term relationships
with one million or more participants of diverse backgrounds
from across the United States and to create a large
biomedical dataset for health research. In this voluntary
program, people provide information about their health andhabits, biological samples, and access to their electronic
health records.

Dr. Bruce Y. Lee, Professor at the City Universityof New York, talks about the potential for AI andother technologies to inform approaches topersonalized nutrition.

Dr. Cindy Davis discussed food and nutrition research
priorities at the United States Department of Agriculture(USDA). These included how food is produced, the effects
of food processing, assessing the nutritional value of foods,
and how well various nutritional needs are met. She notedthat the USDA’s Agricultural Research Service maintains
FoodData Central, a publicly accessible web tool thatprovides current nutrition information about a wide variety
of foods.
Dr. Andrea Wong from the Council for Responsible Nutrition(CRN) – a trade organization for the dietary supplement andfunctional food industries – gave an industry perspective.
She discussed new tools and technologies that companies
use to assess a person’s nutritional needs and the effects of
dietary supplementation. Such approaches have led to newscientific discoveries that are shared with the public.
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The Young Investigator Award finalists pose with
Drs. Emily Ho and Maret Traber from the LPI (left)and Dr. Eric Ciappio from the Balchem Corporation(right).

Healthspan Research Keynote Panel
Speakers: Matt Kaeberlein (Optispan), Holly Van Remmen (OMRF),
and David Furman (Buck Institute)
This panel discussion centered around maximizing the healthy periodof our lives and delaying the declines associated with aging. Each panel
member highlighted a slightly different approach.
Dr. Matt Kaeberlein is the founding director of the University ofWashington’s Healthy Aging and Longevity Research Institute and theCEO of Optispan. He spoke about the need to separate fact from fiction in
the field of aging, including pushing back against current fads likecalorie-restrictive diets, intermittent fasting, and the use of aging “clocks.”
Dr. Holly van Remmen is a professor at the Oklahoma Medical Research
Foundation (OMRF), where her research focuses on frailty – a common
problem for adults of advanced age. She spoke about the involvementof mitochondrial dysfunction in muscle wasting that occurs with aging
and the need for additional study in this area. It is possible that targetingtherapeutics to the mitochondria may be one key to reverse this decline.
Dr. David Furman is an Associate Professor and Director of the
Bioinformatics Core at the Buck Institute for Research on Aging and cofounder of Edifice Health, Inc. His work seeks to use artificial intelligence
technologies to integrate the interpretation of various blood markers
into an easy-to-understand health score and develop it as a markerof biological age. Edifice uses this score to provide its clients with asummary of their immune system and actionable interventions to
reduce inflammation and – ideally – the risk for disease.

Philenroza Thavrin, a student researcher
from the Stevens laboratory at the LPI,
presents her poster on the impacts of
intravenous vitamin C in cancer patients.

Other Sessions ofDiet and Optimum Health 2023:• How Big Data Informs Optimal
Nutrition• Nutrition and the Microbiome• Healthy Aging Interventions• Fortifying an Aging Immune System• Slowing the Decline: Healthy
Cognitive Function with Age
More information about all of these sessions
can be found on the Diet and Optimum Healthconference website.

Evidence for New Vitamin C Recommendations?
One of our invited speakers was Dr. Anitra Carr from the University of Otago,
Christchurch. Dr. Carr’s presentation focused on factors that influence vitamin C
concentrations in the body. She and her colleagues examined vitamin C status inlarge datasets collected in the United States and Europe.
Their results suggest that certain groups might need more dietary vitamin C
than others to achieve the same vitamin C blood concentrations. Age andbiological sex were minor factors, but higher body weight, regular smoking
habits, blood markers for diabetes mellitus, and high circulating C-reactive
protein (also known as CRP, a blood marker of inflammation) were the more
influential factors.

References
Carr, Block, and Lykkesfeldt
Nutrients 14 (2022);
doi: 10.3390/nu14071460
Carr and Lykkesfeldt
Nutrients 15 (2023);
doi: 10.3390/nu15071657

For example, their data showed that people who weigh over 220 lbs could need
up to three times as much vitamin C as those who weigh half as much. This canbe at least partially explained as a dilution effect, as a larger body needs more
vitamin C than a smaller one. It is thought that heavy smoking, the presence ofdiabetes, or high CRP levels can all increase reactive oxygen species in the body,thus explaining an increased need for vitamin C.
Although smoking status is already considered in the RDA for vitamin C set by
the National Academy of Medicine, the other factors listed here are not. In all,this information from Dr. Carr suggests a personalized approach to vitaminrecommendations might be needed for everyone to achieve optimum vitamin C
status.
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LINUS PAULING INSTITUTE
DIGITAL DIGEST
Alexander Michels, Newsletter Editor
Victoria J. Drake, Associate Editor
Sandra Uesugi, Assistant Editor
Oregon State University
307 Linus Pauling Science Center
2900 SW Campus Way
Corvallis, Oregon 97331
phone: 541-737-5075
fax: 541-737-5077
email: lpi@oregonstate.edu
website: lpi.oregonstate.edu