This study, which utilized the gold standard
method of stable isotopes, reinforces that NMN cannot cross the
cell membrane directly and must first be converted to NR
ChromaDex Corp. (NASDAQ:CDXC), a global authority on
Nicotinamide Adenine Dinucleotide (NAD+) research and healthy
aging, shares findings from a preclinical study, as reported in the
peer-reviewed journal International Journal of Molecular Sciences
by a team of scientists led by Dr. Yue Yang, Assistant Professor of
Research in Pharmacology at Weill Cornell Medicine in New York.
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Outside of the cell, NMN cannot cross the
cell barrier directly and must first be converted to NR (Graphic:
Business Wire)
This preclinical study utilized stable isotopes, the gold
standard method in research, to assess the metabolic fate of
nicotinamide mononucleotide (NMN). The results indicate that NMN is
primarily converted to nicotinamide and nicotinamide riboside (NR)
before being utilized for NAD+ synthesis, with only a small portion
of NMN being directly incorporated into NAD+. These results build
on a growing body of research demonstrating that NMN cannot cross
the cell membrane directly and must first be converted to NR.
Because NR can cross the cell membrane directly, this data, along
with other science, indicates that NR is a more efficient NAD+
precursor than NMN.
“The research overwhelmingly demonstrates that NMN obtained from
the diet or supplementation is a precursor to NR as NMN cannot
efficiently cross the cell membrane and suggests NR is more
efficient at increasing NAD+ levels,” said Dr. Anthony Covarrubias,
Principal Investigator at UCLA David Geffen School of Medicine,
Department of Microbiology, Immunology, and Molecular Genetics,
UCLA Metabolism and Immunology Theme Space, who was not involved in
the study.
Although NAD+ was discovered over a century ago, interest in the
science around NAD+ biology has ignited due to the recent discovery
of NR and NMN’s ability to boost bioavailable NAD+. However, in
November 2022, the U.S. Food & Drug Administration determined
that NMN could no longer be sold as a dietary supplement. This
decision has no impact on NR, which is a chemically and
biologically distinct precursor to NAD+.
Chemical structure differences of NR and NMN
NR and NMN are chemically identical except for a phosphate group
present within the structure of NMN. This phosphate group prevents
exogenous NMN from entering the cell directly. NMN’s phosphate
group is removed by the extracellular enzyme, CD73, converting NMN
into NR. A comparison of two separate clinical studies featuring
healthy middle-aged to older adults who received 1000 mg of NR or
NMN daily showcased that NR was 25% more effective in raising whole
blood NAD+ levels after two weeks of supplementation. Additionally,
because of the additional phosphate on NMN, an individual must
consume approximately 15% more NMN (~345mg), compared to 300mg of
NR to deliver the same amount of NAD+ precursor molecules (Conze et
al., 2019 and Pencina et al., 2022).
While one published preclinical study claimed the NMN
transporter, Slc12a8, allows NMN to enter cells directly, these
results were obtained in mice and never replicated in humans
(Grozio et al., 2019). By comparison, five preclinical studies have
demonstrated that NMN cannot cross the cell barrier directly and
must first be converted to NR to increase NAD+ (Fletcher et al.,
2017, Nikiforov et al., 2011, Ratajczak et al., 2016, Kim et al.,
2020, Suave et al., 2023). In contrast, NR is directly imported
into human cells by a family of equilibrative nucleoside
transporter (ENT) proteins (Kropotov e al., 2021).
About the study
The preclinical study led by Dr. Yang provides insights into
NAD+ homeostasis and the precise effects of NMN in mice.
10-week-old male mice were administered isotopically-labeled NMN
(500 mg/kg) both intravenously and orally and NAD+ synthesis was
analyzed after 2 or 4 hours.
Study highlights
- The liver had the highest increase in NAD+ levels after NMN
administration, but it actively broke down NMN releasing it in the
blood, and preferred utilizing nicotinamide and NR instead of NMN
for NAD+ production
- The kidney and small intestines showed significant
incorporation of NR for NAD+ production from NMN
- There was a very small amount of direct incorporation of NMN
into NAD+ in the kidney and white adipose tissue, however levels
were nominal
The results indicate that NMN is primarily converted to
nicotinamide and NR before powering the crucial synthesis of NAD+
and only a small portion of NMN was directly incorporated into
NAD+. This understanding of the conversion pathways sheds light on
the dynamics of NAD+ metabolism in different tissues and is
consistent with a large body of evidence suggesting NMN must be
converted into NR prior to entering cells.
Further, another recent preclinical study analyzing NR and NMN
demonstrated that while both NMN and NR protect DNA, there was a
stronger preventative effect against DNA damage when cells were
treated with NR before chemotherapy versus NMN (Qiu et al.,
2023).
These results add to the growing body of science establishing
that NR is a more efficient and superior NAD+ precursor compared to
NMN, however more research must be conducted to determine the
effects of NR and NMN supplementation on the full NAD+
metabolome.
For additional information on ChromaDex, visit
www.chromadex.com.
About ChromaDex:
ChromaDex Corp. is a global bioscience company dedicated to
healthy aging. The ChromaDex team, which includes world-renowned
scientists, is pioneering research on nicotinamide adenine
dinucleotide (NAD+), levels of which decline with age. ChromaDex is
the innovator behind NAD+ precursor nicotinamide riboside (NR),
commercialized as the flagship ingredient Niagen®. Nicotinamide
riboside and other NAD+ precursors are protected by ChromaDex’s
patent portfolio. ChromaDex maintains a website at
www.chromadex.com to which ChromaDex regularly posts copies of its
press releases as well as additional and financial information
about the Company.
Forward-Looking Statements:
This release contains forward-looking statements within the
meaning of Section 27A of the Securities Act of 1933, as amended,
and Section 21E of the Securities and Exchange Act of 1934, as
amended, including statements related to whether this research
builds on a growing body of evidence showcasing that exogenous NMN
must be converted to NR, making NR a more efficient NAD+ precursor
to NMN. Statements that are not a description of historical facts
constitute forward-looking statements and may often, but not
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forward-looking statements include the impact of the COVID-19
pandemic on our business and the global economy; our history of
operating losses and need to obtain additional financing; the
growth and profitability of our product sales; our ability to
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consumer perceptions of our products; our reliance on a single or
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uncertainties associated with our business and financial condition.
More detailed information about ChromaDex and the risk factors that
may affect the realization of forward-looking statements is set
forth in ChromaDex's Annual Report on Form 10-K for the fiscal year
ended December 31, 2022, ChromaDex's Quarterly Reports on Form 10-Q
and other filings submitted by ChromaDex to the SEC, copies of
which may be obtained from the SEC's website at www.sec.gov.
Readers are cautioned not to place undue reliance on these
forward-looking statements, which speak only as of the date hereof,
and actual results may differ materially from those suggested by
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to reflect events or circumstances after the date hereof.
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ChromaDex Media Contact: Kendall Knysch, Head of Media
Relations & Partnerships 310-388-6706 ext. 689
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