Adirondack Sports January 2024

JANUARY 2024 39
NON-MEDICATED LIFE
Potential Benefits of
Advanced Cholesterol
Testing, PART TWO
By Paul E. Lemanski,
MD, MS, FACP
Medicines are a mainstay of
American life and the healthcare
system not only because they
are perceived to work by the individuals
taking them, but also because
their benefit may be shown by the
objective assessment of scientific
study. Clinical research trials have
shown that some of the medicines
of Western science may reduce the
risk of Type 2 diabetes, heart attacks,
strokes, cardiovascular death and
even some cancers.
In the first 112 installments of
the Non-Medicated Life, a healthy
diet and lifestyle has been shown to
accomplish naturally for the majority
of individuals most of the benefits
of medications in the prevention of
the chronic medical conditions mentioned
above. In order to maximize the
benefit of lifestyle changes, it is best to
first establish a baseline of laboratory
tests of so called “surrogate markers”
of risk. Markers such as fasting blood
sugar, Hemoglobin (Hgb) A1C, total
cholesterol, HDL (the good cholesterol)
and LDL (the bad cholesterol)
and Triglycerides (blood fats) are routinely
followed serially to determining
increasing or decreasing risk.
After a discussion with your primary
care physician or cardiologist, additional
cholesterol-based testing may be
helpful. “Advanced” cholesterol testing
such as High Sensitivity C-Reactive
Protein (HS-CRP), Apolipoprotein
B (Apo B), Trimethylamine-N Oxide
(TMAO), and Nuclear Magnetic
Resonance LipoProfile (NMR Lipo-
Profile) may offer additional identification
of risk – and when measured
serially (at a series of time points) may
help direct and refine lifestyle choices.
Editor’s Note: This is the 113th in a
series on optimal diet and lifestyle
to help prevent and treat disease.
Any planned change in diet, exercise
or treatment should be discussed
with and approved by your personal
physician before implementation. The
help of a registered dietitian in the
implementation of dietary changes is
strongly recommended.
In this two-part article, Part One
addressed the first two advanced tests
(HS-CRP and Apo B) in the November
2023 issue: adksports.com. Part Two will
now address the remaining advanced
tests (TMAO and NMR LipoProfile).
Please note: another important advanced
test Lipoprotein A or Lp(a) that does
not respond to lifestyle changes was
addressed in its own article and will not be
discussed here – see Non-Medicated Life:
An Important New Test Beyond Routine
Cholesterol Testing in the January 2023
issue: adksports.com.
Trimethylamine-N Oxide (TMAO) is
a test developed at the Cleveland Clinic to
help explain why some individuals with
“normal” cholesterol levels still develop
heart disease. TMA (Trimethylamine) is
produced by gut bacteria (gut microbiome)
acting upon lecithin, choline, and
carnitine from dietary sources. TMA is
then absorbed from the gut and travels
to the liver where it is oxidized to TMAO.
TMAO is then released back into the circulation
where it may damage the endothelial
cells that line arteries. This damage
then allows LDL, or the “bad” cholesterol,
to penetrate the arterial wall and form a
cholesterol plaque – the necessary first
step in atherosclerosis.
The potential dietary sources of lecithin,
choline and carnitine are red meat,
eggs, dairy products and fish. Eating sufficient
amounts of any or all of these may
result in the selection and overgrowth of
gut bacteria that can metabolize TMA.
Experiments done with broad spectrum
antibiotics that suppress such bacteria
show a suppression in TMAO. In experiments
in which both regular meat eaters
and vegans were given a steak dinner, the
regular meat eaters subsequent TMAO
blood level was elevated, but the vegans
did not show an increase in TMAO.
Only by increasing the frequency of meat
consumption in vegans was an increase
in TMAO recorded. It appears that by
increasing the frequency of meat consumption
it is actually possible to alter
the gut microbiome population to favor
bacteria that can metabolize TMA.
TMAO may help answer the question:
how much meat may I eat (and still be
healthy from a cardiovascular perspective)?
Because TMAO levels are also,
in part, determined by your genetics,
measurement may provide individualized
feedback on the safe frequency and
amount of consumption of red meat, fish
and dairy products. Of course, the saturated
fat content of red meat consumed
is also important, as saturated fat will
increase the concentration of LDL in the
blood. Thus, substituting filet mignon
(lower saturated fat) for porterhouse
(higher saturated fat), as well as decreasing
portion size and frequency of consumption,
may lower cardiovascular risk
as shown quantitatively by measuring
both TMAO and LDL cholesterol.
Nuclear Magnetic Resonance Lipo-
Profile (NMR LipoProfile) is a specialized
blood test in which blood samples are
subjected to NMR analysis in a manner
similar to MRI of solid tissues. The NMR
LipoProfile allows a delineation of the size
distribution of LDL and HDL particles in
the blood and a quantitation of particle
number. You will recall that LDL and HDL
in the blood exists as spherical particles.
These particles are heterogenous in size,
meaning that there are small, medium,
and large sized LDL and HDL particles.
This becomes potentially an important
consideration because different size particles
appear to be associated with different
levels of risk. For example, so called
small, dense LDL particles (smaller in
size than average LDL, and denser in that
they contain relatively more protein) are
more likely to form plaques than so called
large, fluffy LDL particles (larger in size
than average LDL, and fluffy in that they
contain more of a fat called triglyceride).
The distribution of these particles in
a normal individual follows a bell curve,
with few small LDL on one end, few large
LDL on the other end, and medium size
particles in between representing the
majority. The area under this particle
distribution bell curve is what is typically
reported as your LDL number in
milligrams per deciliter (mg/dL). By
changing the shape of this bell curve,
to have the “hump” of the curve toward
one side or the other, may change the
number of high-risk particles or lowrisk
particles, without changing the
total area under the curve. Thus, the
benefit of the NMR LipoProfile may be
knowing the LDL subclass distribution
and not only the total LDL in mg/dL.
Moreover, lifestyle changes may
alter the particle distribution markedly.
For example, exercise and weight loss
result in predominately more large,
fluffy LDL particles and fewer small,
dense LDL particles, even if the LDL in
mg/dL does not change appreciably.
Patients are often upset that instituting
an exercise program did not lower their
LDL appreciably in mg/dL. The NMR
LipoProfile may help to quantitate the
benefit and provide valuable feedback
that encourages continuation of beneficial
lifestyle changes.
In summary, the determination of
global cardiovascular risk is helped
with the measurement of “surrogate
markers” of risk, most commonly the
standard cholesterol profile, assessed
over time, to identify increasing or
decreasing risk. Diet and lifestyle, as
well as medications may appreciably
change risk. After a discussion with
your primary care physician or cardiologist,
additional testing may be
helpful. Beyond routine cholesterol
testing, advanced tests may offer a way
to further refine risk. Moreover, such
advanced testing – such as HS-CRP,
Apo B, TMAO, and NMR LipoProfile
– when measured
over time, may
provide additional
quantitative feedback
on how you
may further lower
risk and help direct
and refine lifestyle
choices.
Paul E. Lemanski, MD, MS, FACP
(plemanski3@gmail.com) is a boardcertified
internist practicing internal
medicine and lifestyle medicine in
Albany. Paul has a master’s degree
in human nutrition, he’s an assistant
clinical professor of medicine at
Albany Medical College, and a fellow
of the American College of Physicians.