Specific protein transporters
called monoamine transmitters exist that transport monoamines into or out of a cell. These
are the dopamine transporter (DAT), serotonin transporter (SERT), etc.
Monoamine oxidase (MAO) is an enzyme that breaks down monoamine neurotransmitters
after they have been released into the synapse.
transporter (DAT) is a membrane-spanning protein that binds the neurotransmitter dopamine and performs
re-uptake of it from the synapse into a neuron. DAT is present in the peri-synaptic area of
dopaminergic neurons where dopamine signaling occurs. DAT terminates the dopamine signal and is
implicated in many dopamine-related disorders.
is an integral membrane protein that removes dopamine from the synaptic cleft and deposits it into surrounding cells,
thus terminating the signal of the neurotransmitter dopamine.
is a symporter that moves dopamine across the cell membrane. DAT was found to be enriched in
dendrites and cell bodies of neurons in the SUBSTANTIA NIGRA. This pattern makes sense for a
protein that regulates dopamine levels in the synapse.
Results suggest that dopamine re-uptake may occur outside the synaptic specializations once dopamine diffuses from
the synaptic cleft. In the substantia nigra, DAT appears to be specifically transported into dendrites
where it modulates the entra-cellular and extra-cellular dopamine levels of nigral dendrites.
The rate at which DAT removes dopamine from the synapse can
have a profound effect on the amount of dopamine in the cell, best evidenced by motor abnormalities.
Decreasing levels of DAT expression are also associated with aging and likely are underlying reasons for decreases
in dopamine released as a person ages.
Acetyl L-Carnitine (ALCAR)
are no harmful side effects. ALCAR is non-toxic.
It is also known as Vitamin BT. It is synthesized from Lysine and Methionin but enough B1 (Thiamine)
and B6 (Pyridoxine) must be available.
It is used for
fatty acid transport (FAT) and is required for entry into the mitochondria and removal of organic acids which frees
the entramitochrondrial coenzyme. It is used for energy supply within the cell, muscles, assists in prevention
of fats in the muscles. It improves antioxidant affect of Vitamins C & E.
It reduces the risk of poor fat metabolism. In long-term administration
in rats, it restores a synaptic pattern comparable to that of young rats.
Antioxidant concentrations are shown to be low in the substantia nigra with most severe neuron depletion with
age. Acetyl L-carnitine is being investigated as a determinant of neuronal longevity.
ALCAR can counteract the age-dependent reduction of several receptors in the CNS of rodents such as neurotransmitters
and others, thereby enhancing the efficiency of synaptic transmission and appears to reverse age-associated deficits
in cellular function, in part by increasing cellular ATP production.
It transports fatty acids into the mitochondria and increases the rate in which fat is burned.
It contributes positive effects on muscles, heart immune cells, brain nerves, and sperm. R-Alpha Lipoic Acid (R-ALA):
Typical dose: 100-200 mg three times per day. There are no significant side effects.
Food sources include spinach, broccoli and potatoes. Lipoic acid (R-ALA) is non-carcinogenic and
shows no evidence of target organ toxicity.
It is found in every cell in the
body. It is thought that certain nerve diseases are at least partially caused by free radical damage.
Free radicals are hypothesized to play a role in neuropathy. In diabetes, nerve cells leading to
the arms and legs become damaged, resulting in numbness, pain, etc. It neutralizes free radicals in
both fatty and watery regions of cells.
levels of glutathione (an antioxidant in the brain). It is produced by the body
and decreases with age. It acts as a coenzyme in cellular energy production. It
chelates heavy metals and recycles vitamin E and C. The R form of R-ALA is biologically active and native
to the body. It significantly reduces inflammations. It is immediately available to
cells in the R-ALA form. It is a co-factor in aerobic metabolism, specifically the pyruvate dehydrogenase
complex. R-ALA has the ability to modify gene expression by stabilizing a transcription factor for treatment
of various cancers.
Lipoic acid is able to regenerate
(reduce) antioxidants such as glutathyione, Vitamin C & E, thus maintaining a healthy cellular redox
state. Studies of rat aging suggest that R-ALA and L-Carnitine result in improved memory and delay
mitochrondrial decay. As a result, it is helpful for Parkinson’s disease and Alzheimer’s.
R-ALA chelates mercury intoxication. It can penetrate the blood-brain barrier and cell membrane.
Lipoic acid is essential to oxidative decarboxilization of keytones. In pyruvate dehydrogenase,
complex lipoic acid links with a Lysine residue and results in reversible ring open/closing in the
oxidation of A-keto acids.
Deficiency of lipoic
acid results in: reduced muscle mass, failure to thrive, brain atrophy, and increased lactic acid
accumulation. Lipoic acid is involved in the conversion of carbohydrates to energy. When
sugar is metabolized in the production of energy, it is converted to pyruvic acid. When there is plenty
of oxygen available to the cell, pyruvate is broken down by an enzyme complex that contains lipoic acid, thiamine and niacin.
When the oxygen supply is low, the cell converts pyruvate acid to lactic acid. During exercise,
lactic acid tends to accumulate and leads to muscle fatigue. Lipoic acid supplementation may help
improved energy metabolism as an antioxidant. It improves diabetic neuropathy.
It also aids in stimulating the regeneration of nerve fibers. It increases
glucose uptake by muscle and nerve cells and protects cells from glycation. R-ALA prevents excess
glucose reaction with proteins to create cross-links that damage vital proteins, including the myelin sheath of neurons.
With decreased bodily production of lipoic acid with age mitochondrial
energy production becomes less efficient and more free radicals are generated. Lipoic acid protects
cells, particularly in the mitochondria where most oxygen damage occurs.L-Tyrosine (TH):
MAOIs may result in hypertensive crisis. The potentiation of sympathomimetic substances
and related compounds by MAO inhibitors may result in hypertensive crises. Individuals taking phenelzine
should avoid sympathomimetic drugs (including amphetamines, cocaine, methylphenidate, dopamine, epinephrine and norepinephrine),
or related compounds (including methyldopa, L-dopa, L-tryptophan, L-tyrosine and phenylalanine). Tyrosine
increases sensitivity to stimulants. Other drugs which tyrosine may interact with include: opiates
Dosage: Daily dose divided into
3 or more doses daily. Sensitivity side affects are observed in as low a dose as 200-500 mg.
Recommend starting at 100 mg, 30 minutes prior to a meal. Do not exceed 4 grams per day.
N-Acetyl Tyrosine has inferior bioavailability.
containing tyrosine include cheese, which is also an extremely high source of glutamine because casein inhibits
protein breakdown in the body.
Tyrosine converts to L-dopa
to dopamine to norepinepherine to epinephrine. Tyrosine as a precursor to L-dopa,
a precursor to dopamine and requires biopterin (a folate derivative). H4biopterin,
the co-enzyme of TH, is reduced to about 50% in the brain of PD patients.
The key enzyme in H4biopterin biosynthesis is the quinoidH2pteridin reductase.
H4biopterin is formed from H2pterin by an enzyme called quinoiddihydropteridinreductase
(DHPR), an enzyme that needs NADH as a central co-factor.
Tyrosine is therefore one of
the possible rate-limiting enzyme for the creation of dopamine. Increasing tyrosine availability
could have the ability to increase dopamine synthesis. Tyrosine increases all catecholamine levels
and increases plasma neurotransmitter levels. Some neurons become more sensitive to tyrosine availability.
Fatigue during exercise is contributed in part to the increase of
serotonin and increase in the ratio of serotonin to dopamine. Tyrosine may help decrease this ratio and
compete with tryptophan (the precursor to serotonin). Increased dopaminigeric activity may decrease the
perception of fatigue.
Tyrosine has been reported in
the treatment of Parkinson’s to elevate dopamine as measured by levels of a dopamine metabolite.
One study associated combined administration of tyrosine, 5-HTP,
and cardbidopa. Tyrosine can potentiate the effects of various drugs, allowing a lower dose to be
equally effective. No toxicity levels have been observed.
Tyrosine is involved in the synthesis of neurotransmitters in the brain. Tyrosine is
a precursor to L-dopa, dopamine, and others. Tyrosine requires biopterin (a folate derivative),
NADPH and NADH (forms of niacin), copper and Vitamin C. Conversion of tyrosine requires Vitamin B-6,
folic acid and copper. It may serve as a valuable adjunct therapy in the treatment of Parkinson’s
disease. Tyrosine is used by cells to synthesize proteins.
Tyrosine functions in part of the signal transduction process; which is transmitted by using glutamate;
as the nitrogen source. Tyrosine phosphorylation is considered to be one of the key steps
in signal transduction and regulation of enzymatic activity.NADH - Nicotinamide Adenine Dinuleotid:
NADH is known as CoEnzyme -1 or as Co-E1.
NADH capsules produce time-released action, increasing bioavailability absorption.
Stimulates manufacture of Dopamine, Noradrenaline & Serotonin by stimulating Tyrosine
to L-Dopa, NAD+ (Redox reduced to NADH) synthesized from tryptophan (Quinolinic acid).
NADH stimulates cellular production of the neurotransmitters of dopamine, noradrenaline
and serotonin. It is directly involved in the cellular immune defensive system and DNA repair.
NADH is the reduced form of NAD with high-energy hydrogen (H), which
provides energy to the cell. Hydrogen, in its biologically active form (the negative charged hydrogen
ANION), is what gives energy to your body’s cells, activating cell metabolism and cell regeneration. The
negatively charged hydrogen, with its extra electron, is a highly efficient antioxidant, which is able to neutralize free
radicals. NADH is the natural biological carrier of H-.
It is effective in combating disorders such as fibromyalgia and chronic fatigue syndrome.
NADH Study #1:
of dopamine could be blocked at the metabolic conversion from tyrosine to L-dopa. The enzyme
catalyzing this reaction is tyrosine (TH). The activity of which is considerably diminished in substantia
nigra of Parkinson’s. H4biopterin, the co-enzyme of TH, is reduced to
about 50% in the brain of PD patients. Taking this into account, we consider a new concept
to overcome the dopamine deficit, namely to stimulate TH activity in order to increase L-dopa biosynthesis.
However, H4biopterin does not show any beneficial effects with PD. The failure of this approach
was the impermeability of the blood-brain barrier for H4biopterin. Therefore, this substance cannot reach
its target, the substantia nigra.
is whether it is possible to stimulate the H4biopterin biosynthesis in the brain. If
a diminished biosynthesis H4biopterin is the cause of TH defect, stimulation of H4biopterin biosynthesis should elevate the
The key enzyme in H4biopterin
biosynthesis is the quinoidH2pteridin reductase (10). This enzyme needs NADH
as a co-enzyme. The idea was to stimulate H4biopterin biosynthesis by applying NADH, which
increases quinonoidhtpteridine reductase activity. Owing to this NADH may stimulate endogenous L-dopa
To investigate the concept, 800 PD patients were treated
with NADH. NADH has been studied in a dopamine producing neuroblastema cell-line.
Results of study group: The maximum improvement of orally applied
NADH was 60%. The motoric ability improved considerably.
When neuroblastoma cells were incubated with NADH, dopamine production was observed. The stimulation
was independent from the tyrosine supplied, indicating that the substrate tyrosine is not the limiting factor, but the enzyme
or the co-enzyme respectively was the limiting factor.
TH (L-trosine) activity was measured directly after NADH had been added to a culture medium, a 75% increase could be observed.
This finding indicates that NADH is able to stimulate TH activity directly.
L-dopa biosynthesis may occur via enhanced production the TH enzyme H4biopterin.
Levels of H4biopterin in the brain of PD patients are reduced by 50%. If the
deficit of H4 is due to a decreased biosynthesis, the biochemical mechanism of NADH may be explainable. H4biopterin
is formed from H2pterin by an enzyme called quinoiddihydropteridinreductase (DHPR), an enzyme
that needs NADH as a central co-factor. There is indirect evidence that DHPR influences TH
activity via H4biopterin biosynthesis, because substances which completely inhibit DHPR such as MPTP induced PD
Therefore, we have to rely on indirect evidence,
one of which is the metabolic product of dopamine and homovanillinic acid (HVA). The level of this substance
increases after NADH treatment.
Furthermore, tissue culture
experiments show that NADH is able to increase dopamine production. Indirect evidence for this assumption
is derived from the assumption that dopa inhibitors such as carbidopa in combination with NADH yield a better and longer-lasting
This new therapeutic principle,
namely the stimulation of the endogenous L-dopa biosynthesis could overcome the drawback of the L-dopa treatment in the
sense that it could avoid further destruction of the residual Ingra cells caused by the action of radicals, which are formed
in considerable quantities by oxidation of L-dopa.
Vitamin D 3:
The role of Vitamin D3 in
degenerative diseases is becoming more obvious every year. Vitamin D3 is obtained from sunlight and stays
longer in the body than supplements.
Disease is a result of selective loss of dopamagenic neurons in the substantia nigra region of the brain.
In PD, the cause and mechanism of continued neuron cell death is currently unknown. We hypothesize,
based upon several lines of evidence, that documented chronically inadequate Vitamin D intake is a significant factor in
the pathogenesis of PD. This hypothesis implies that a dietary aid for prevention and therapy for PD is
possible. Currently the tolerable upper intake level tolerance is approx. 2000 IUs per day (50 mcg).
There’s evidence of lack of adverse affects in clinical trials that used intake of 1250 mcg/day Vitamin D3.
In a test tube, Vitamin D3 increased cell output of GDNF.
GDNF:This is the abbreviation for the Glial
cell-Derived Neuropathic Factor (GDNF). This small protein promotes survival of many types of neurons.
This gene encodes a highly conserved neurotropic factor. A form of this protein has shown to
promote survival and differentiation of dopaminergic neurons in culture, and was able to prevent apoptosis of motor neurons.
A mature form of the protein is a ligand.
The most prominent feature of GDNF is its ability to support the survival of dopaminergic and motor neurons.
These neuronal populations die in the course of Parkinson’s disease.
The GDNF family of ligands (GFL) consists of four neurotropic factors:
GDNF, NRTN, ARTN & PSPN. GFLs play a role in cell survival, neurite outgrowth, cell differentiation
and cell migration. In particular, signaling by GDNF promotes the survival of dopaminergic neurons.
GFLs are distantly related to the transforming
growth factor super family of proteins and belong to the cystine knot protein family.
GFLs function as homodimmers at the cell
surface of target cells. At the cell surface, a signaling complex forms composed of a:
GFL, dimmer, a receptor tyrosine, and a cell surface bound co-factor.
Consequential phosphorylation of these tyrosines then initiate intra-cellular transduction processes.
GFLs are an important therapeutic target
for several conditions: GDNF has shown promising results in Parkinson’s disease clinical
trials. GDNF is a potent survival factor for central motor neurons.
NRTN can also be used for Parkinson’s disease therapy
to promote survival of basal forebrain cholinergic neurons and spinal motor neurons. Given the huge
spectrum of possible therapeutic applications, the modulation of GFR receptor complex activity is of great interest.
However, as GFLs are unable to penetrate
the blood-brain barrier, creation of agonists for development of effective therapies against neurological diseases are desired.
side affects include anorexia, nausea, abdominal bloating, gastrointestinal pain and diarrhea. Medications
of high niacin to treat high cholesterol can deplete choline (a derivative of lecithin).
Toxicity: No toxicity. Recommended dosage: 100-600 mg daily
Lecithin breaks down to choline, which reacts to form acetylcholine
or phosphatidylserine which breaks down to form phosphatidylcholine.
Choline supplementation is also used therapeutically to reduce cholesterol levels.
Lecithin is usually used as a synonym for pure phosphatidylcholine.
Phosphatidylcholine is an important component of the mucous layer or mucosa in the large intestine. The
mucous layer forms the mucosal barrier, protecting the large intestine from attacks by bacteria. Lecithin
is an essential part of cell membranes and can be easily and totally metabolized.
The major source of lecithin is soybean oil. The main phosolipids in lecithin from soy and sunflower
are phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine, and phosphatidic acid.
Choline is essential in the manufacture of the neurotransmitter acetylcholine and
is the main component of our cell membranes, such as phosphatidylcholine (lecithin) and sphingomyelin.
Choline supplementation also increases the accumulation of acetylcholine within the brain.
Choline is also required for the proper metabolism of fats. Choline,
like Vitamin B12, SAM-e and folic acid, acts as a methyl-donor. It's essential for proper liver
function. It’s required for the export of fat from the liver. Choline as a methyl-donor
also helps conserve carnateine and folic acid.
also provides liver support, by increasing solubility of cholesterol and inhibiting platelet aggregation as a result of
its high content of linoleic acid.
Disease is characterized by the general destruction of nerve cells in several key areas of the brain.
It’s possibly related to the decrease of available acetylcholine, which functions as a transmitting agent
in the brain.
Phosphatidylserine, a derivative of choline
(Lecithin derivative), is mostly found in neural cell membranes. The serine molecule in phosphatidylserine
is attached mostly to DHA (Omega-3 fatty acid) – (Fish Oil). Phosphatidylserine
in soy is basically serine attached to fatty acids. Phosphatidylserine is the major phosholipid
of brain synaptic membranes. It plays a crucial role in several membrane-linked activities
such as: enzyme activation, liposome function, ion permeability, maintenance of the cell’s internal
environment, secretory vesicle release, cell-to-cell communication, and cell growth regulation.
Phosphatidylserine supplements are made by enzymatically preparing soybean lecithins
and L-serine by a phosphilipase reaction. Toxicity: No toxicity. Recommended dosage:
100-600 mg daily
Phosphatidylserine modifies: glucose
metabolism in the brain, catecholamine, and acetylcholine release, NMDA receptor density and function and
muscarinic acetylcholine receptor density. The primary mechanism is the enhancement of cholinergic
In rats, Phosphatidylserine restores acetylcholine
and increases acetylcholine receptor density.
increases cholinergic function in multiple ways:
it maintains membrane potential.
it increases calcium uptake, as this is important in neurotransmitter release.
Third, Phosphatidylserine affects exocytosis of neurotransmittors by interacting
with membrane-binding proteins. Phosphatidylserine increases turnover of dopamine
in the brain and in the striatum. It also increases dopamine released in the limbic area and cerebral
cortex. Phosphatidylserine also prevents age-related deficits in NMDA receptor function in the forebrain.
Phosphatidylserine mediates a variety of processes related to synaptic
plasticity, information storage, and glutamatergic transmission.
It also acts as an antioxidant, suppresses cytotoxic factors & interacts with nerve growth factor (NGF).
It reduces circulating levels of stress hormone cortisol.
It decreases post-exercise cortisol levels and reduces muscle soreness.