Researchers outline strategy for testing ketone bodies against COVID-19
Review highlights the role of geroscience in the fight against this and
future pandemics

Date:
July 15, 2020
Source:
Buck Institute for Research on Aging
Summary:
A new review encourages researchers studying metabolism and immunity
to turn their attention to ketone bodies, which are being widely
studied for their role in aging, as a possible therapeutic against
COVID-19, seasonal flu and other respiratory infections.



FULL STORY ========================================================================== Given the disproportionate impact that COVID-19 has on older adults
in terms of death and lasting disability, and the impact of common aging-related comorbidities like diabetes and cardiovascular disease,
Buck Institute professor and practicing geriatrician John Newman,
MD, PhD, can make a compelling argument that those infected with the
SARS-CoV2 virus are suffering from an aging-related disease, no matter
how old they are when they get infected. In a review published in Med,
a Cell Press journal, Newman and a consortium of colleagues encourage researchers studying aging, metabolism, and immunity to turn their
attention to ketone bodies, which are being widely studied for their
roles in aging and aging-related diseases. The research team views
ketone bodies as a possible therapeutic against COVID-19, seasonal flu
and other respiratory infections.


========================================================================== Ketone bodies are compounds naturally produced during fat metabolism. They provide energy to cells and can also reprogram cellular functions. Eating
a ketogenic diet -- which is high fat, low protein, and low carbohydrates
- - ramps up the production of the primary ketone beta-hydroxybutyrate
acid (BHB).

While the purported and reported benefits of eating the strictly
controlled diet have made ketogenic-related food products and supplements wildly popular, Newman, senior author of the review, is quick to point out
that there is much unknown about the biology of BHB and the physiology of
how it impacts various systems in the body. "I want to be clear that there
is no evidence that a ketogenic diet is protective in any way against COVID-19," he said. "In fact there may be instances where BHB could
promote viral replication of SARS-CoV2, the specific virus that causes
the disease. But given the promise that BHB shows against many of the age-related risk factors for COVID-19 such as heart disease and diabetes
we want to take advantage of this unique opportunity to bring geroscience
to the fight against COVID-19. " Small clinical trials in humans have
shown proof-of-concept that BHB can improve cardiac function in those
with heart failure and improve key aspects of cognitive health. In the laboratory setting BHB shows promise against type 2 diabetes and dampens harmful inflammation. Elevation of blood ketones has been shown to be
broadly protective against hypoxia-related tissue damage, which occurs in severe respiratory infections. Doctors at Johns Hopkins University plan on testing a ketogenic diet on a small group of intubated patients suffering
from COVID-19. The hope is that the diet will improve oxygen exchange,
reduce the duration of time on ventilators and perhaps most importantly,
reduce the systemic inflammation that leads to the cytokine storm that
often proceeds the development of acute respiratory distress syndrome.

"Basic research shows that BHB directly inhibits the activation of
the pro- inflammatory pathway NLRP3, which is central to the disease pathogenesis of COVID-19 and is a likely contributor to the cytokine
storm," said Brianna Stubbs, PhD, a Buck researcher with expertise
in ketone biology and lead author of the review. "Understanding how
BHB impacts innate immunity following infection is one of the key
preclinical questions we hope researchers will be eager to tackle."
"Dying is not the only bad outcome from COVID-19," says Newman. "Some
survivors are presenting with long-term severe memory impairments, extreme exhaustion and weakness from muscle wasting following an extended time
in the hospital." Pointing out the fact that BHB and other ketones act
on multiple systems in the body, the authors are hoping for clinical
studies that test ketone supplementation as a way to bolster muscle
function and attenuate or avoid delirium among those who have been
infected. Key preclinical and clinical questions are included in the
review and are detailed at http:// www.impactmetabolism.org.

"Age-related risk factors are putting older adults at particular peril for COVID-19. Those that survive it, no matter what their age, can emerge with symptoms that are associated with aging," said Newman. "Studying ketone
bodies in this current environment not only holds promise in the fight
against COVID- 19, but the research is also likely to yield results that
could help all of us live better longer in the absence of a pandemic."
Other researchers involved in the study include Eric Verdin, President
and CEO of the Buck Institute; Andrew P Koutnik, Institute for Human
and Machine Cognition; Emily L. Goldberg, Department of Physiology,
University of California, San Francisco (UCSF); Vaibhav Upadhyay,
Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF;
and Peter J. Turnbaugh, Department of Microbiology and Immunology, UCSF.

This work was supported by NIH K08 AG048354, Buck Institute institutional funds, and NIH T32 HL007185.

John C. Newman and Eric Verdin are co-founders of and shareholders in BHB Therapeutics LTD., which is developing products relating to ketone bodies.

Brianne J. Stubbs is a shareholder of HVMN Inc., which markets products relating to ketone bodies and of BHB Therapeutics Ltd. John C. Newman,
Eric Verdin and Briana J. Stubbs are inventors on patents related to the
use of ketone bodies. John C Newman is on the scientific advisory board
of Virta Health, Inc. Eric Verdin is an advisor to Keto Fuel, Inc. Peter
J. Turnbaugh is on the scientific advisory boards for Kaleido, Pendulum,
Seres, and SNIPRbiome.

All other authors declare no competing interests.


========================================================================== Story Source: Materials provided by
Buck_Institute_for_Research_on_Aging. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Brianna J. Stubbs, Andrew P. Koutnik, Emily L. Goldberg, Vaibhav
Upadhyay, Peter J. Turnbaugh, Eric Verdin, John
C. Newman. Investigating Ketone Bodies as Immunometabolic
Countermeasures against Respiratory Viral Infections. Med, 2020;
DOI: 10.1016/j.medj.2020.06.008 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200715131230.htm

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