DrG's Medisense Feature Article
17091-Nitric_Oxide
Fad
Supplement: Nitric Oxide Pills
by Ann Gerhardt, MD
August 2017
Print Version
Bottom
Line At the Top:
Save your money to buy healthy vegetables and protein foods rather than
“nitric oxide” supplements which don’t
contain nitric
oxide anyway. Nonetheless, understanding the role of nitric
oxide
is interesting and important.
You can’t buy nitric oxide pills because it’s a
gas.
That doesn’t keep pill pushers from labeling their product as
nitric
oxide (NO), even though what they’re selling are ingredients
that
your body MAY turn into NO. They don’t tell you
that there
is no guarantee that your body will do so.
Ads tell you that their product improves strength and power with weight
training and enhances the body’s production of nitric oxide,
a
natural blood-flow enhancer good for a healthy heart, blood pressure
and circulation. The labels must say that their claims have
not
been evaluated by the FDA and that their product is not intended to
diagnose, treat, cure or prevent any disease. But that
doesn’t keep them from scaring the unwary consumer with
“signs of NO deficiency,” listed as fatigue,
unhealthy
blood pressure and “No signs at all,” meaning
anyone.
They confirm your need for their product with NO test strips, which
measure salivary nitrate, not NO.
The only accurate statement in these ads relates to the fact that NO
signals blood vessels to relax and dilate, promoting healthy blood
pressure and cardiac function. Arginine, one of the common
pill
ingredients, might improve muscle building, but by way of a non-NO
mechanism.
The main ingredient of most NO products is arginine, an amino acid that
we normally get from protein foods. Other products, often
made
from beets, contain nitrate found naturally in vegetables.
The body has enzymes that turn arginine into NO, but that
doesn’t
happen willy-nilly. If it did, our blood pressure would
bottom
out and we would pass out from lack of blood to the
brain.
NO generation is regulated and doesn’t automatically surge
with
an arginine influx from a pill, even though, as a gas, it
doesn’t
last more than a few seconds in blood.
Vegetable nitrate follows a different path to NO. Bacteria in
the
mouth reduce beet or spinach nitrate to nitrite, which is
swallowed. Stomach acid may convert nitrite to NO, or it may
be
absorbed into the body and flushed out in urine or turned back into
nitrate. The salivary glands take up nitrate from blood and
concentrate it in saliva, so it can be swallowed and go through the
whole process again. Nitrates naturally abundant in water
follow
a similar fate.
NO actually has an interesting history. Joseph Priestly
discovered it in 1774, 2 years after discovering nitrous oxide, or
laughing gas. While nitrous oxide went on to intoxicate
people at
laughing gas parties and later to be used as an anesthetic, NO
languished in obscurity.
In 1846, Italian chemist Ascanio Sobrero synthesized nitroglycerin and
realized that it was explosive. Why he decided that tasting
his
explosive compound might be a good idea has been lost to history, but
in doing so, he discovered that it causes a blow-your-head-apart type
of headache. Scientists attributed the headache to dilated
blood
vessels. Since angina pectoris, the chest pain often preceding a heart
attack, is caused by the heart’s arteries not delivering
enough
blood, nitroglycerin was used for its treatment. It opens the
heart’s blood vessels, allowing blood and oxygen to reach
heart
muscle and alleviate pain.
More than 200 years after Priestly’s discovery, scientists
finally elucidated how nitroglycerin works and NO’s role in
the
body. They proved that nitroglycerin and other nitrates
dilate
blood vessels only after their conversion to NO, which is responsible
for regulating arteries’ relaxation or
constriction. They
found that cells in blood vessel walls make NO. They
identified
nitric oxide synthase (NOS) as the enzyme in the cells that generates
NO from arginine. NO’s role in controlling vascular
tone
and contributing to heart muscle function led to the journal Science
naming it the “Molecule of the Year” in
1992. The
scientists who figured it out received the Nobel Prize in Physiology or
Medicine in 1998.
Since then we’ve learned much more. Nitroglycerin
not only
relaxes the walls of blood vessels, but also relaxes heart
muscle. It relaxes the main airway into the lungs and inhaled
NO
dilates the lung’s blood vessels in people with lung
disease. It relaxes the muscles and sphincters of the
gut.
Nitroglycerin relaxes just about any spasm except that of skeletal
muscles, which are the ones attached to bones. NO also plays
a
role in energy metabolism, the immune system and brain
health. It
contributes to memory, vision, pain perception, sense of smell and
nerve function throughout the body. NO regulates how prone
blood
is to clot. Even erectile dysfunction drugs are related to
NO: They work by maintaining NO-induced blood vessel swelling
in
the penis.
Unfortunately, the NO story is not entirely glorious. Too
much of
a good thing might be bad. Unconstrained blood vessel
relaxation
markedly drops blood pressure below the level necessary to keep the
brain and organs alive. This is called shock, and happens in
severe infections in which bacterial toxins stimulate too much NO
production. When immune cells in the brain make too much NO,
it
can be toxic and cause convulsions. NO made by immune cells
helps
to knock out infectious organisms and tumor cells, but it also turns
off white blood cell activation that should be fighting
infection.
NO might also be oxidized to ‘reactive oxygen
species’
(ROS), which are toxic. Inflammatory conditions, such as
rheumatoid arthritis and colitis, and even mild inflammation, common in
obesity and heart disease, favor ROS formation. Diarrhea,
fever
and infection accelerate NO’s oxidation to nitrate.
NOS in cells of blood vessels, heart and brain putters along,
constantly making NO in greater or lesser amounts to maintain
health. This NOS is highly regulated and in normal people
makes
just the right amount of NO to maintain health. Other NOS,
particularly that in immune cells, turns on and off, kicking into
action when needed in response to infection, stress and
inflammation. NOS regulation is often abnormal in people with
diabetes, inflammatory conditions, high blood pressure,
atherosclerosis, high cholesterol and some nutritional
deficiencies. They tend to make less NO and are resistant to
its
beneficial effects.
Because of normal NOS regulation, there is no guarantee that arginine
from food or a supplement will be converted to NO. The body
just
might decide to do something else with it, such as use it to build
protein, convert it to creatine in muscle or break it down into urea to
be flushed away in urine. Similarly, dietary nitrate may or
may
not be converted to NO, alternatively ending up in urine or saliva.
Experiments with arginine or beet juice supplements have been rather
underwhelming. Normal folks don’t derive any
benefit with
respect to lowered blood pressure or boosted immune function.
Beet juice downed by young athletes in a Penn State study did not
enhance blood flow to exercising muscles in spite of relaxed vessels at
rest.
Supplement effects in people with diabetes, high blood pressure, high
cholesterol and heart disease is more complicated. Taking
arginine supplements or drinking large amounts of beet juice does relax
their blood vessels, but studies haven’t shown a survival
benefit. In heart attack patients NO helps to grow blood
vessels
around the clogged ones, so supplements (or a better diet) may be
helpful, but this hasn’t been proven. Short-term
arginine
supplementation relaxes leg arteries in people with poor circulation,
but the effect is lost over the long-term. Beet juice may
make
diabetics’ heart muscle less stiff but often without an
improvement in blood pressure.
Do we need arginine supplements to make adequate NO?
No.
The “internet” tells us that the daily arginine
requirement
is about 4-6 grams, but that is malarky as long as we eat enough
protein. Arginine is one of the amino acids that the body can
make from other amino acids. Assuming normal intestinal,
kidney
and liver function, we just need to eat a healthy amount of protein to
ingest or synthesize sufficient arginine. Good food sources
of
arginine are protein foods – meat, fish, poultry, dairy,
legumes,
corn, nuts, egg and whole grains.
There is no dietary requirement for food nitrates, but everyone should
be eating multiple vegetable servings daily. Green
vegetables,
beets, carrots, cabbage and radishes are good nitrate
sources.
The Dietary Advice to Stop Hypertension (DASH) diet requires nine
vegetable and fruit servings daily. We’ve credited
DASH’s high potassium and bioflavonoid content with lowering
blood pressure, but perhaps its nitrate content helps too.
Will taking arginine or beet supplements hurt you? People
whose
kidneys don’t work well should not be loading up on extra
amino
acids like arginine. Those with drug-induced or hereditary
methemoglobinemia should avoid high nitrate foods, since they can
precipitate a crisis. People with kidney stones should avoid
high
nitrate vegetables which are also high in oxalate.
So, what to do? Eat a varied diet with adequate protein and
plenty of vegetables. If you like beets and spinach, eat
them. Avoid infections. Most of all prevent or
treat the
conditions that cause defective NO regulation, by maintaining an ideal
weight and doing regular, moderate exercise.╣