DAT (dopamine active transporter):
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),
Monoamine oxidase (MAO) is an
enzyme that breaks down monoamine neurotransmitters after they have been released into the synapse.
The dopamine 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.
DAT 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.
DAT 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
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)
There 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.
the risk of poor fat metabolism. In long-term administration in rats, it restores a synaptic pattern comparable
to that of young rats.
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
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.
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.
It increases 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.
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 and L-dopa.
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.
Foods 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.
Nicotinamide Adenine Dinuleotid:
NADH is known as CoEnzyme
-1 or as Co-E1.
Requires Enteric-coated NADH capsules produce time-released
action, increasing bioavailability absorption.
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-.
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
The question 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 enzyme activity.
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 biosynthesis.
NADH Study Group #2:
the concept, 800 PD patients were treated with NADH. NADH has been studied in a dopamine producing neuroblastema
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.
When 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.
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 symptoms.
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 clinical improvement.
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.
Parkinson’s 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.
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
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.
Lecithin:Lecithin’s 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
down to choline, which reacts to form acetylcholine or phosphatidylserine which
breaks down to form phosphatidylcholine.
supplementation is also used therapeutically to reduce cholesterol levels.
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.
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.
Choline also provides liver support,
by increasing solubility of cholesterol and inhibiting platelet aggregation as a result of its high content of linoleic acid.
Alzheimer’s 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.
supplements are made by enzymatically preparing soybean lecithins and L-serine by a phosphilipase reaction. Toxicity:
No toxicity. Recommended dosage: 100-600 mg daily
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 transmission.
Phosphatidylserine restores acetylcholine and increases acetylcholine receptor density.
Phosphatidylserine increases cholinergic function in multiple ways:
First, it maintains membrane potential.
Second, it increases calcium uptake, as this is important in neurotransmitter
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.
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).
reduces circulating levels of stress hormone cortisol. It decreases post-exercise cortisol levels and reduces