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The
following cofactors need to be used
along with the amino acid precursors:
·
Vitamin C
1,000 mg per day
·
Vitamin B6
75 mg per day
·
Calcium 500
mg 500 mg per day
In addition,
·
Cysteine
4,500 mg per day in equally divided
doses
·
Selenium 400
mcg per day and
·
Folic acid
2,000 mcg to 3,000 mcg per day
should also
be used to prevent depletion of the
methionine-homocysteine cycle (figure 5)
by L-dopa and presumably by L-tyrosine
from which L-dopa is synthesized from,
the immediate precursor of L-dopa.
Administration of L-dopa leads to
depletion of S-adenosyl-methionine
(SAMe), a component of the
methionine-homocysteine cycle which is
the one carbon methyl donor of the body;
proper levels of SAMe are needed in
order for norepinephrine to be
methylated to epinephrine. Long-term use
of L-dopa without proper administration
of amino acids of the
methionine-homocysteine cycle leads to
depletion of epinephrine.37
There
is a, “total loss” of sulfur amino acid
associated with treatment of
Parkinsonism with L-dopa as evidenced by
the loss of total glutathione which
occurs.41
Depression
NeuroResearch Clinics Approach
Figure 5:
“The methionine - homocysteine cycle”,
the heart of the sulfur amino acids.
Glutathione is synthesized in a side
chain reaction off the
methionine-homocysteine cycle, see
figure 5. The loss of total glutathione
leads to a state where the body’s most
powerful detoxifying agent (glutathione)
is no longer functioning properly and is
unable to neutralize further toxic
insult leaving the patient in a state
where more toxic damage is facilitated.
All patients taking L-dopa and/or
L-tyrosine need to be supplemented with
adequate levels of sulfur amino acid to
prevent depletion of the
methionine-homocysteine cycle, depletion
of glutathione, depletion of
epinephrine, and the other components
dependent on the methionine-homocysteine
cycle. While administration of any of
the sulfur amino acids in the cycle is
adequate if the dosing is high enough
cysteine is chosen since it costs only
about eleven cents per day wholesale.
Selenium 400 mcg per day needs to be
administered with cysteine to prevent
cysteine (sulfur amino acids) from
creating an environment that contributes
to central nervous system neurotoxicity
from methylmercury. Administration of
cysteine can potentially facilitate
concentration of methylmercury into the
central nervous system.46
Selenium binds irreversibly to
methylmercury in the central nervous
system rendering the methylmercury
biologically inactive and non-toxic.47
Folic acid
is required in order to provide optimal
function of the folic acid cycle which
in turn prevents hyperhomocysteinemia
from preventing the
methionine-homocysteine cycle from
functioning properly. As noted
previously, without proper
administration of amino acids of the
methionine-homocysteine cycle leads to
depletion of epinephrine. It would
appear the second factor driving
epinephrine levels beyond
methionine-homocysteine cycle depletion
is hyperhomocysteinemia. It can take 3
to 6 months for hyperhomocysteinemia to
return to normal when proper levels of
folate, vitamin B6 and vitamin B12 are
provided for. It appears to be no
coincidence that it can take 3 to 6
months for epinephrine levels to return
to normal a fact that appears to
parallel homocysteine improvement.
When
the goal of treatment is to prevent
depletion of neurotransmitters by
prescription drugs or in associated
situations where prescription drugs are
no longer working effectively during
treatment due to the neurotransmitter
levels falling too low from depletion
due to circumstance set up by the drug45,
the patient should be placed on the
level 1 amino acid dosing (see Table 1)
along with the prescription drug,
cysteine, selenium and folate. While
amino acid precursors when used alone
properly are highly effective, a
drug/amino acid combination may be
desirable with severe disease, such as
the suicidal patient, the catatonic
patient, or the patient that is unable
to take part in normal day-to-day
functions such as work. Supplementing
with amino acid precursors allows
reuptake inhibitors to continue to
function optimally without
tachyphylaxis.
When
amino acids are used as the initial
therapy, start all patients on the level
1 dosing protocol along with cofactors
and proper methionine-homocysteine cycle
support at the first visit. Patients
should return in one week, at which time
focus on how the patient’s symptoms the
previous day. Asking about the previous
day’s symptoms is more indicative of
changes in the system brought about by
amino acid therapy since it takes 3 to 5
days for the full effects of starting or
changing an amino acid dosing to be
displayed.
If
symptoms are not fully under control in
one week, increase to the level 2 dosing
along with cofactors and proper sulfur
amino acid support and instruct the
patient to return in one week. At the 3rd
visit, if symptoms are not under
control, increase to the level 3 dosing
along with cofactors and proper sulfur
amino acid support and have the patient
return to clinic in one week. If in one
week symptoms are not under control,
continue the level 3 dosing and obtain a
urinary neurotransmitter test of the
caliber provided by laboratory under the
direction of a hospital based laboratory
pathologist.40 Follow the
amino acid dosing recommendations
returned generated after review of
testing preformed under the supervision
of a board certified laboratory
pathologist. Patients should return in
one week to discuss results and amino
acid dosing changes that may be needed.
Any time an amino acid dosing change
occurs, patients should return in one
week to evaluate the results. Over 60%
of patients tested needed only one
neurotransmitter test. This is
consistent with complete resolution of
symptoms after adjusting the amino acid
dosing in accordance with the consultant
recommendations on the test.
When
treating depression, if amino acid
dosing changes establish both the
serotonin and dopamine in the phase 3
therapeutic range (see urinary
neurotransmitter testing below) and no
relief of symptoms is achieved, consider
the possibility of depressive bipolar
disorder. Under treatment with the
amino acid protocol approximately 2% of
patients are found to suffer from
depressive bipolar disorder that has not
been previously diagnosed. The primary
care physician at this point should
continue the amino acids and initiate a
psychiatric referral in order to affect
starting of a mood stabilizing bipolar
drug. It is noted that as long as the
amino acids are continued, over 99% of
patients started on mood stabilizing
drugs such as lithium, Depakote, or
Lamictil find complete resolution of
depression on the standard starting
dose.
Depression
NeuroResearch Clinics Approach |
