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(Make a copy for your doctor!)

I had CFS/FM for 20 years and have devoted thousands of hours over the
last 6 years researching this weird illness.  Only recently have I
developed a strong theory which indicates that, for various reasons,
nitric oxide (NO) is dysregulated causing most of the symptoms of this
disease.

NO is produced by many cells in the body in response to increased
production of cytokines in inflammatory condition and the state of
hyperactive immunity associated with this illness.

NO is the most potent vasodilator know to man.  The upregulation of this
simple gas dilates the blood vessels of the lower extremities and could
easily explain neurally mediated hypotension and reduced brain
perfusion.  NO is also excreted by the lymph nodes in response to
bacteria, etc., causing the nodes to swell.

Excessive NO is released by the cartilage cells of the joints and
increases sensitivity to pain as much as 10 fold.  Since NO is a gas, it
can go in and out of solution depending on barometric pressure. As a
gas, NO can come out on solution when pressure is reduced, and can be
specially bothersome when the atmospheric pressure drops on the approach
of bad weather.

Excessive production of NO can down regulate the production of adrenal
hormones and cause adrenal insufficiency (low cortisol), which can
result in sodium loss and hypovolemia.

Decreased production of cortisol down regulates the production of red
blood cells.

Increased production of NO down regulates hemoglobin levels and
interferes with hemoglobin's ability to utilize iron, creating a form of
iron deficiency anemia.  But there's a difference in the type of anemia
caused by upregulated NO.  The stored iron level in the cells is normal,
but the utilization of iron by hemoglobin is reduced in effect causing a
form of  iron deficiency where iron levels are normal on measurement.

Since hemoglobin is the only substance that cleans (scavenges) excessive
nitric oxide from the system, any minor problem with hemoglobin or red
cell numbers will reflect in increased nitric oxide.

This entire process is one of a "vicious circle."  You could have
suffered an illness for few months during which your cytokines were
elevated increasing nitric oxide to upper levels.  The increased nitric
oxide in turn down regulated adrenal output (cortisol).  Cortisol acts
as the brake of the immune system so once cortisol is down, immune
activity is increased.  Red cell numbers fall and hemoglobin is alter,
thereby reducing the scavenging of nitric oxide, down regulating the
cortisol and on and on in a "vicious circle" of chronic disease.  The
original "cause" of your sickness could easily have subsided, yet you
are still caught in this "vicious circle."

One way around this is to increase the cortisol activity, which will
down regulate cytokines and lower nitric oxide production.  Increasing
cortisol will also increase the red cell numbers.  At the same time, you
should  do everything you can to lower nitric oxide levels by other
means.

But, and here's the big problem, taking regular doses of  hydrocortisone
(cortisol) over the length of time required to increase the red cell
count to midrange (borderline-low red cell counts is a hall mark of this
illness) will feedback to the adrenal gland and down regulate your own
production of cortisol no matter what Tittlebaum says.  The adrenal
gland does not recover normal production if it has been down regulated
for any length of time.  Most doctors know the danger of too much
hydrocortisone!

There is a safe way around this.  11-beta hydroxysteriod dehydrogenase
is the enzyme that deactivates your own production of cortisol.  If you
could someway inhibit this enzyme, your own production would remain
bioactive in your system for much longer and do much more work  Since
inhibiting 11 beta hydroxysteriod dehydrogenase does not increase the
level of cortisol, rather it only increases the time cortisol remains
bioactive, there is no feedback to the adrenal.

It just so happens that glycyrrhizin in licorice extract  is an
inhibitor of 11 beta hydroxysteriod dehydrogenase.  Licorice extract can
increase cortisol activity by 6 fold when taken in doses of 3-5 grams
day.  But don't take much more because licorice increases nitric oxide
production at doses higher than 3-5 grams.  In addition, 3-5 grams per
day is a relative asafe dose even for people with borderline
hypertension as long as they are not salt sensitive.  Since licorice
extract increases blood pressure by increasing sodium retention, only
salt sensitive hypertensive people should avoid licorice extract.  If
salt don't bother you, licorice won't either.

It takes licorice extract about 3 hours to be metabolized and to
maximally inhibit the enzyme, therefore, if you take a very low dose of
hydrocortisone (<2.5 mg day) 3 hours after taking the licorice dose, the
hydrocortisone is potentated by ~6 fold and does the job of 15 mg of
cortisol without much danger of feedback.  Take licorice extract and
low-dose hydrocortisone on a 2 day on, one day off schedule and the
chance of any feedback problems to the adrenals is reduced to zero!

The increased cortisol activity will help you retain sodium and make you
feel better within hours, but it will require about three months to
build your red cell count back to midrange.

If during this period, you eat lots of liver (the prescription for
fatigue 50 years ago) and take a few other meds to keep nitric oxide
down regulated, you blood should return to its old
nitric-oxide-scavenging ability and should break the "vicious circle"
and completely recover.

I am 90% recovered.  The only thing standing in my way of announcing my
complete recovery is to loose the extra weight I gained.

Studying NO, I found out that increased NO causes insulin sensitivity
and hypoglycemia so I went on the Atkin's high protein diet and have
steadily lost 3 pounds a week for the last month.  My energy level is
also increased by not eating high-glycyemic foods.

You can read my rough notes on nitric oxide and licorice and CFS/FM at
my web site located at:  http://www.serve.com/licorice  Look for the
links to the nitric oxide theory.

Good luck,
Dave Williams