The nitrates ingested through the juice appeared to be
successfully absorbed by the body. When looking at the
two groups given nitrates (with or without medication) in
comparison to the two groups given placebo, there was a
large increase in NOX (shorthand for nitrate plus nitrite)
by 0.52μmol/L, or 2.7-fold the concentration these subjects
had at the beginning of the trial.
cGMP, the signalling molecule produced after nitric oxide,
also increased 1.4-fold, supporting the idea that nitric oxide
itself was stimulated after supplementation. Nitric oxide
itself cannot be measured in a living human since it is a
rapidly synthesized and rapidly destroyed molecule, with an
elimination half-life measured in milliseconds.
There were no changes in transcutaneous arterial methaemoglobin
(a biomarker of oxygen delivery), heart rate,
or any other glycaemic, biochemical, or haematological
biomarker in either group. It appears that out of these measures,
the only clinically relevant change was the desired
increase in total NOX and cGMP. The changes observed
did not differ in subjects who were or weren’t on medication,
as everybody experienced an increase in these desired
biomarkers.
The increase in NOX and cGMP was notably measured in
a fasted state in the lab, not immediately after nitrate ingestion.
When supplementation ceased for two weeks, these
readings reverted to normal. This provides evidence that
a daily dose of nitrates is enough to support your body for
at least 24 hours, though these benefits will be lost in two
weeks if supplementation is not maintained.
When looking at the daily blood pressure readings taken by
the subjects themselves, nitrate consumption appeared to
cause a significant reduction of systolic blood pressure after
a single week. Nitrates continued to have a time-dependent
benefit all the way up to the last week of supplementation,
reaching their peak efficacy of an 8.1mmHg/3.8mmHg
reduction in systolic/diastolic blood pressure. Again, these
changes were not accompanied by any changes in heart rate.
There was some variance between subjects, as this final reading had a wide 95% confidence
interval of 3.8-12.4mmHg systolic and 0.7-6.8mmHg diastolic, but every subject
who took nitrates saw some degree of reduction in blood pressure.
The other blood pressure measurement, ambulatory blood pressure (ABP), displayed
similar benefits. When compared to their baseline levels, the subjects who took nitrates
daily experienced an average reduction of 7.7mmHg systolic and 2.4mmHg diastolic.
There were not any major fluctuations throughout the day in the ABP. Nitrates induced
a sustained reduction of blood pressure over both sleeping and waking hours of similar
magnitude.
The secondary measurements taken in this study were related more to blood flow rather
than pressure, which is a useful biomarker in and of itself, as increases in blood flow are
cardioprotective even if blood pressure does not change.
Pulse wave velocity (PWV) was reduced by 0.59m/s in the subjects taking nitrates
when compared to their baseline values and to a similar magnitude (0.58m/s) when
compared to placebo, as this parameter was not changed with the nitrate-depleted placebo.
PWV reductions of this magnitude have been associated with sizeable decreases
in heart disease risk[3]. AIx and FMD both saw significant benefits as well. These measurements
were reduced by 5.2% and increased by 1%, respectively, while the placebo
group experienced no changes.
These findings support the use of nitrate not only as a blood pressure-reducing agent,
but also as a supplement that could benefit overall circulatory health. Based on the
significant improvement in the measurements of arterial stiffness and the reliability of
arterial stiffness as a biomarker of cardiovascular disease mortality in all age groups,
this further supports the role of nitrates in heart health. However, a subgroup analysis
of whether this benefit to arterial stiffness applied to all subjects found that only the
subjects who were on medication experienced the decrease in PWV.
Finally, similar to how two weeks cessation caused the elevations of plasma NOX and
cGMP to return to normal levels, when nitrate was no longer used by hypertensive participants
their blood pressure and blood flow returned to baseline levels. This indicates
that nitrates are not curative, but rather a ‘band-aid’ supplement that exerts its benefits
for only as long as it is used.
Nitrate ingestion did not appear to be associated with any significant side-effects clinically,
biochemically, or hematologically. Urine and feces were reported to change color
in all groups due to the red coloration of the beet juice, which was an expected outcome.
The pigments of beets, known as betalains, are eliminated in both urine and feces in a form which is still colored red, and leads to many people
thinking their juice caused acute kidney or rectal trauma.
There were no adverse interactions reported in the subjects
using medication in regard to drug-drug interactions, suggesting
a role for dietary nitrates as an adjuvant therapy
(something to be taken alongside the ‘main course’ pharmacotherapy;
adjuvants are the side-dishes of medicine).
While the four subjects that dropped out were all subjects
using medication, it was not determined to be relevant to
the study, since they dropped out prior to receiving their
placebo or nitrate supplementation and were split evenly
between groups.
People supplementing with nitrates experienced a reduction in blood pressure for up to two weeks after supplementation had ceased.