Sports supplements and ergogenic aids
SUMMARY
,Lecture Nitrate
NO metabolism
Nitric oxide is an important molecule in the body. It has various physiological roles and until
about 25 years ago we really thought that nitric oxide could only be formed through the L-
Arginine pathway. That is an oxygen dependent pathway. So, when there is enough oxygen
available, we can reduce L-arginine through a certain series of steps into NO, which happens
predominantly in the vascular wall. It also happens in the brain and other neural areas. We
use Nitric Oxide Synthase enzymes (NOS) for that pathway. By doing this, you also produce
nitrite (NO2-) endogenously (inside your own body), because NO itself is quite volatile. It
appears and within a few seconds it is gone already. Nitrite and Nitrate are then being
formed as byproducts of this pathway. The nitrite and nitrate that we have in our body
floating around in the systemic circulation in our blood is mostly being formed as a
byproduct of NO metabolism.
It was discovered that nitrate when it is in your body/circulation can be transformed back
into nitrite and this can be reduced back into NO. You can also produce NO in this reversed
pathway. This is more under hypoxic and low pH conditions. When we don’t have a lot of
oxygen available, this is a pathway which we can use to compensate potentially, for a
reduced working of the normal L-arginine pathway which works under oxidative conditions.
Knowing that, there is a lot of substances that contain a lot of nitrate inside it in terms of
food products, it was quickly suggested that if we ingest these food products (e.g.,
concentrated beetroot juice), nitrate, nitrite levels in the blood are elevated and we can use
that in the nitrate nitrite NO pathway to produce more NO. This seems to be the case. The
suggestion was that if we ingest more dietary nitrate, we can stimulate this reverse pathway
and produce more NO in that manner (outside from the L-arginine pathway). Which could
be beneficial under hypoxic or low pH conditions, but also in conditions where the normal L-
arginine pathway is not working properly. This happens in a lot of metabolic or
cardiovascular diseases.
NO is a very important physiological substance. So, we have L-arginine on the right side
which is oxygen dependent and dietary nitrate on the left side which we now call the nitrate
,nitrite NO pathway. We ingest dietary nitrate; you increase nitrate in your circulation, you
also increase nitrite in your circulation, in that way you can produce more NO in this reverse
pathway. That is important since NO plays a role in many physiological processes. Exercise
efficiency, mitochondrial respiration, Ca2+ handling, vasodilation, glucose uptake and muscle
fatigue are very important for exercise performance. If you stimulate these processes, it
may be beneficial for exercise performance.
What happens when we ingest nitrate? This explains the time that you need to have
between ingestion and any potential ergogenic effects that may appear. If you ingest nitrate
from any substance, it obviously comes into your mouth. You chew on it and swallow it, get
it through your stomach, and it normally appears in the upper part if the digestive tract (of
the intestines). That is where (most of) the nitrate is being absorbed. That is what we call
the ‘first passage’. If it gets absorbed, it enters your circulation (into the blood) and you see
an increase in nitrate concentration in your blood. That blood is being transported
throughout the whole body. There is an active uptake of nitrate from the blood in the
salivary glands, so in the mouth. The concentration is 20-25% higher than in the normal
circulation. It is now in the mouth/saliva. The nitrate is now in free form, and it is turned
into nitrite by bacteria in the mouth. The oral microbiome is important for the conversion of
nitrate into nitrite. You then swallow that again; it comes into the stomach and there is now
nitrite in the stomach. Within the stomach, some of the nitrite is immediately reduced into
NO which can than have certain physiological effects in the stomach. The rest is then
transported into the intestines. It is taken up again and that is when nitrite in the
plasma/blood is increasing. This is called the ‘second passage’. The nitrite is transported
throughout the entire body and in various tissues it can be reduced into NO. 25% of the
nitrate is taken up by the salivary glands, the rest is excreted in the urine. 5-7% of total
nitrate is being reduced to nitrite. So when you look at graphs of nitrate and nitrite you see
that the unit that is being used is different because the concentrations of nitrite is much
lower than the concentration of nitrate.
, First human studies
They know that NO is a vasodilator, the first thing that should happen is a reduction in blood
pressure. You dilate your vessels; blood pressure goes down. After three days of
supplementation, blood pressure was measured. It can be seen that nothing happens with
systolic blood pressure, but there is a reduction in diastolic blood pressure. This was the first
time that somebody shows in humans that if you provide people nitrate, quickly afterwards
see a reduction in blood pressure.
Looking back at the picture of the physiological roles of NO, it appears that
vasodilation producing NO in the reverse pathway is able to produce NO locally, in the
circulation/endothelial wall, thereby dilating your vessels and reducing blood pressure.
Lower O2 cost submaximal exercise
They tried to translate these findings to exercise performance measures. After
supplementation period they cycled on a bike at different submaximal intensities until
maximum. They measured oxygen consumption (VO 2), and heart rate. For the heart rate
nothing happens. But for oxygen consumption they showed that at each exercise intensity,
the bar for nitrate is lower than the bar for the control condition. So, for each exercise
intensity either with or without nitrate supplementation, they saw that you need less
oxygen to cycle at that intensity. You can reduce oxygen consumption at submaximal
intensities if you ingest a certain amount of dietary nitrate.
What they then did is to see if really become better if you consume less oxygen. They also
did a time to exhaustion trial in that same study you see that everyone except one person
did better in the beetroot juice condition versus the placebo. So, they could last longer at a
certain intensity. They saw a 16% improvement.
