Excess NO may be responsible for causing glaucoma and possibly
other conditions: how to address this naturally: There has been
much publicity in the press recently about a finding that many people
suffering with chronic open angle glaucoma (COAG) have excessive
levels of Nitric Oxide (NO) (Neufeld 97).
By reducing these levels through drugs, researchers were able
to reduce the damage caused by increased intraocular pressure to
the optic nerves in rats (Neufeld 99). There is now a rush by pharmaceutical
companies, to get a NO-blocking drug approved for the treatment
of COAG. However, there seems to be little interest in finding out
what is really causing these levels to be so high in the first place.
Since artificially suppressing any natural physiological response
of the body is bound to have unintended consequences, wouldn't it
make sense to look for the cause and address that instead?
Nitric Oxide: a brief description
Information about this neurotransmitter is still not fully known,
since it was only first identified in 1987 (Ignarro, 1987), resulting
in the authors receiving the 1989 Nobel Prize in Science. Nitric
Oxide is made, at various sites in the body, from L-arginine. It
serves many functions, such as inducing vasodilatation, controlling
intragastric pressure, facilitating dilation of the uterus during
pregnancy, inhibiting bone resorption, is essential for producing
and maintaining an erection, and kills bacteria, fungi, and even
tumor cells. However, it is also very dangerous at high levels,
being a potent nitrogen free radical. It actually has the capacity
to kill neurons and is thought to be responsible for much of the
degeneration that occurs after strokes and in some diseases of the
What are some of the possible causes of increased NO levels?
Based on current knowledge and available research, there are several
factors which may cause or contribute to elevated NO levels:
- Allergies (histamine)
- Poor iron status
- Hypoxia (oxygen deficiency)
- Carbon monoxide exposure
- Excess estrogen or 'estrogen dominance'
How can allergies cause increased NO levels? The answer is quite
simple. It is common knowledge that allergies can cause elevated
histamine levels, which is why antihistamine medications are such
popular drugs. What is not widely known, is that histamine, in turn,
stimulates a release of NO from various cells in the body (Mannaioni
97a, Mannaioni 97b, Champion 98).
It is actually proposed that some of the adverse effects of histamine,
such as increasing permeability of the blood/brain barrier, are
actually mediated by NO (Mayhan 96). Therefore, in individuals with
allergies causing elevated histamine levels, addressing this problem
may abrogate the need for pharmacologically reducing NO levels.
Additionally, high histamine levels have been associated with of
circulatory hypoxia, a condition that will be discussed further
in another section (Sumina 78).
The question of how to address this problem can be done in several
ways, the merits of which will not be explored now, since this is
a topic which deserves more attention than can be given here:
- Avoidance or reduction of allergens (e.g., dietary change,
air filters, etc.)
- Use of natural antihistamines (e.g., quercitin) (Bronner, Pearce)
- Use of conventional antihistamine medications
- Alternative allergy treatment (homeopathy, enzyme-potentiated
- Conventional allergy treatment
For those people with allergies, some of whom may not even know
they have them, one or a combination of the above choices might
help improve not just their allergic symptoms, but their overall
health as well. Of course, in order to adequately address the allergy
problem, it must be properly diagnosed by a qualified clinician.
Poor iron status
Another possible cause of increased NO is decreased iron levels.
One of the reasons for this is that hemoglobin and other iron-containing
compounds bind to NO in the blood, rendering it inactive.
Poor iron status and anemia may result from dietary insufficiency,
not only of iron, but of folic acid and vitamin B-12 as well. Particularly
in the elderly, B-12 deficiency is not uncommon. This is most likely
due to an age-related decline in the production of Intrinsic Factor,
a glycoprotein secreted by cells in the gastric mucosa, necessary
for the proper absorption of B-12. Those at greatest risk for a
deficiency of iron and B-12 are vegetarians and those with a diet
very low in meat, the best source of B-12. However, deficiencies
can be pharmacologically induced as well. As an example, drugs taken
for gastrointestinal problems, such as the popular omeprazole (Prilosec
in the US, Losec in Canada), are known to reduce B-12 absorption
significantly, possibly by reducing IF levels (Marcuard 94).
Even in people with normal hemoglobin levels, their iron stores
may be less than optimal. Many physicians feel that this is more
accurately assessed through the evaluation of serum ferritin levels.
Ferritin is the major iron storage protein, conserving it for use
as needed, in the cells. It also serves other functions, such as
protecting against certain free radicals, such as oxidized iron
and peroxides, and is essential for proper cell growth and proliferation.
Therefore, it is likely that adequate ferritin levels act to reduce
some of the negative effects of excess NO through its antioxidant
function. NO in turn, helps to protect against the release of oxidative
free iron from iron-containing compounds (Puntarulo 97, Juckett
In addition to resulting in reduced hemoglobin and ferritin levels,
iron deficiency may cause elevated NO levels through another physiological
mechanism by causing anemic hypoxia, or subnormal oxygen content
in the blood. Hypoxia is known to cause a stimulation of NO production,
which is most likely a defense or survival mechanism of the body,
which produces the NO to relax the blood vessels in order to supply
more oxygenated blood to the tissues.
Other forms of hypoxia may also be present and have this effect
as well. For example, diffusional hypoxia results from damaged pulmonary
membranes and impaired lung function, as occurs with chronic obstructive
pulmonary disease (e.g., emphysema). Therefore lung diseases may
cause elevated NO levels by causing chronic hypoxia.
As for natural treatments, some nutrients have been shown to enhance
lung function. The most notable of these is N-acetylcysteine, commonly
referred to as NAC.
Impaired lung function may also be pharmacologically induced with
the use of common medications such as beta-blockers. These drugs
have the potential to promote broncho-spasm and broncho-constriction.
This class of drugs is often used for conditions such as hypertension,
cardiac arrhythmia, chronic angina pectoris, and others. Natural
treatments of these conditions and elimination of the necessity
of these drugs may therefore reduce NO levels.
Ironically, the most popular drugs in the treatment of COAG are
beta-blocker eye-drops (e.g., Timolol). Therefore, it is possible
that this type of treatment could raise NO levels and actually increase
the risk of damage to the optic nerve. Additionally, if those glaucoma
subjects in the study by Neufeld et al were being treated with these
medications, it is possible that the elevated NO was not a result
of the condition, but rather the treatment.
A condition of circulatory hypoxia, resulting from excessive vasoconstriction
or myocardial insufficiency, can also cause an increase in NO levels.
Magnesium has been shown to ease vasoconstriction, and other cardio-protective
nutrients, such as coenzyme Q10, L-Carnitine, Taurine, etc. may
prove helpful for myocardial insufficiency.
Carbon monoxide (CO) exposure can cause circulatory hypoxia, a
condition previously discussed, by attaching to hemoglobin and inhibiting
its oxygen-carrying capacity. As a matter of fact, it attaches more
than 200 times stronger to hemoglobin than oxygen (Walker 99). Low
levels of CO exposure may not present any obvious symptoms and therefore,
may go undetected.
These low levels of exposure may also cause symptoms, mimicking
those of the common cold or flu, and may therefore be misdiagnosed
by even the best physicians. This is unfortunate, since there are
now simple breath meters which can detect carbon monoxide levels
(Walker 99), but which are probably rarely used by general practitioners.
Exposure in an industrial work environment is probably the most
common scenario, but can occur in the home as well. This is especially
true in the winter, when heating units are in use and windows are
usually shut tight.
Interestingly, in a study recently published in a Chinese medical
journal, the intraocular pressure in glaucoma patients has been
shown to increase during the winter months (Qureshi 97). Whether
this effect is due to the colder weather, carbon monoxide exposure,
reduced level of physical activities, or some other factor is not
However, it would seem prudent to have carbon monoxide detectors
installed in the home and even at work in order to reduce the chances
of exposure. These devices are especially important since CO is
odorless and colorless, and low levels of exposure may not present
any immediately obvious symptoms. Proper ventilation is crucial
to avoiding CO, especially when there is any combustion taking place,
such as with heating units, gas stoves, and fireplaces.
It should be noted that those people with higher levels of hemoglobin
and red blood cells should be somewhat less susceptible to damage
from low levels of CO, due to their greater oxygen-carrying capacity.
Recently, estrogen has been shown to enhance the bioactivity of
NO (Blum 98). There are several ways that women can wind up with
excessive estrogen levels or an imbalance in the hormonal system,
causing an "estrogen dominance" situation.
One is that women on hormone replacement therapy (HRT) may not
have their hormone levels properly monitored and may be given doses
that cause levels to rise too high. Also, the most popular estrogen
used, Premarin, is obtained from horses and has a completely different
composition than human estrogen, with much more potent estrogenic
effects. There are an increasing number of doctors who are using
"natural" hormone replacement therapy and custom tailoring the composition
and dosages to their patients.
It is also possible that excessive estrogenic activity is being
induced in the body through estrogen-mimicking environmental pollutants.
There may be some detoxification and lifestyle modification procedures
(e.g., eating organically, avoidance of plastics, etc.) that can
reduce these effects. Another possibility is a hormonal imbalance
between estrogen and progesterone.
If progesterone levels are low, a woman can become "estrogen dominant".
Along with the many other adverse effects of this condition, NO
may become too active. Many nutritionally-oriented doctors routinely
check for this, using either salivary or blood tests, and where
needed may prescribe a natural progesterone to be administered either
orally or more commonly, transdermally.
Fluoride poisoning has been shown to cause circulatory hypoxia
(discussed previously), possibly resulting from a tremendous increase
(8 to 9 fold) in histamine levels (Sumina 78). Therefore, it is
not out of the realm of possibilities that lower doses of fluoride
could result in a slight decrease in oxygen carrying capacity. People
could reduce this possibility by not drinking fluoridated water
or commercially prepared beverages, since many of these are made
using fluoridated water.
One final possibility is that some elevated NO levels may be pharmacologically
induced. As an example, it was discussed previously about this possibility
with beta-blocking agents. It is beyond the scope of this paper
to discuss all of the drugs which could possibly elevate NO levels,
but clinicians and patients should be aware that any drug can have
unintended and unwanted consequences.
Possible Dangers of Suppressing Nitric Oxide
Any drug that is developed to suppress NO production, in the hope
of treating COAG or any other condition, could have many adverse
effects, due to the many functions of the neurotransmitter. For
example, NO plays an important role in controlling feto-placental
circulation during pregnancy (Izumi 96), making it's use during
pregnancy potentially dangerous. Suppression of NO could theoretically
cause other problems such as impotence or sexual dysfunction, elevated
blood pressure, digestive disturbances, increased susceptibility
to infection, and even increased risk of cancer.
Nitric Oxide plays a vital role in normal physiological function.
However, in addition to being an antioxidant, it is also a free
radical and can have unwanted negative effects when levels are abnormally
high. It may be possible to ascertain and treat the cause of this
situation through various means, only some of which have been discussed
here. As more becomes known about NO, other conditions beside COAG
may be identified as being caused or exacerbated by excess NO, thereby
opening up new avenues of treatment and hope for many sufferers
of chronic health problems. (2058 words)