Food and Nutrients in Disease Management
able to achieve relief of symptoms with dopamine levels in this range. For treatment of patients with Parkinson’s, the therapeutic range of
urinary dopamine is 6000 to 8000 micrograms of dopamine per gram of creatinine. Dopamine levels of this magnitude can be achieved by administration of the amino acid precursor, L-dopa.
Amino acid supplementation can reduce the tachyphylaxis generally associated with pharmacologic interventions. Once the synaptic levels of dopamine are high enough and the fl ow of electricity is
once again adequate to regulate fi ne motor control, clinical resolution of the Parkinsonian tremor and other symptoms are seen.40 As with Parkinsonism, the damage to other neuron bundles of the serotonin/catecholamine pathways
as seen in depression can be dealt with effectively by increasing the neurotransmitter levels higher than is normally found in the system. This has led our group to propose the Bundle Damage
Theory of Depression.
<b>The bundle damage theory</b>
The bundle damage theory states:Neurotransmitter dysfunction disease symptoms, such as symptoms of depression, develop when the electrical fl ow through the neuron bundles that regulate function is compromised by damage to the
individual neurons or the neuron components composing the neuron bundle which conducts electricity to regulate or control function. In order to optimally restore neuron bundle regulatory function, synaptic
neurotransmitter levels of the remaining viable neurons must be increased to levels higher than is normally found in the system, which restores adequate electrical outfl ow resulting in relief of symptoms
and optimal regulatory function.
Bundles of neurons convey electricity that regulates and/or controls numerous functions in the body. If enough of the individual neurons of a bundle become damaged the fl ow of electricity through the bundle is diminished, leading to the function being controlled and/or regulated not controlling
properly, causing symptoms of disease to develop. Technically synaptic neurotransmitter levels prior to treatment in patients with disease due to neuron bundle damage are in the normal range for the
population.The bundle damage theory and the monoamine theory are not mutually exclusive of each other.Instead these two theories can be viewed a complementary in that they address different mechanisms
of action leading to neurotransmitter dysfunction and compromised electrical fl ow out of the postsynaptic neuron. The monoamine theory addresses low levels of neurotransmitters in the
synapse as the etiology of impedance of electrical fl ow needed to regulate function and keep disease symptoms under control. The bundle damage theory addresses damage to the primarily
postsynaptic neuron structures that impede the fl ow of electricity needed to regulate function and keep disease symptoms under control. With the monoamine theory and the bundle damage
theory the fl ow of electrical energy needed to regulate function is not adequate. Differentiation of the two theories lies in the etiology of the dysfunction. Under monoamine theory returning
neurotransmitter levels to normal will relieve disease symptoms. Under the bundle damage theory synaptic neurotransmitter levels need to be established that are higher than the reference range of
the population.It is the mechanical damage to the postsynaptic neurons as suggested by the bundle damage theory and not the synaptic neurotransmitter levels that is the primary cause of monoamine disease.
This subset is composed of about 88% of adult patients and 100% of the elderly patients with depressive symptoms—the nonresponders from the depression studies above.
Neurons are intended to function for life. Loss of a neuron to apoptosis is permanent, although in limited areas of the brain neurons may regenerate to replace the neurons that have undergone
apoptosis.58 As neurons go into apoptosis in the postsynaptic neuron and become completely nonfunctional they tend to go through an agonizing death where the electrical brilliance with which
they function slowly fades until the electrical fl ow through the neuron regulating function decreases and stops over time.The only way to increase neurotransmitter levels in the central nervous system is to administer
amino acid precursors that cross the blood-brain barrier and are then synthesized into neurotransmitters.Increasing neurotransmitter levels in the synapse is analogous to increasing the voltage in
an electrical wire, whereby turning up the voltage you get more electricity out of the other end of the wire. Turning up the voltage increases the electrical potential (pressure) of the electrons entering a
partially damaged wiring connection, leading to more electrons (electricity) fl owing out of the other end. In the case of neurotransmitter disease where the neurons of the neuron bundles are damaged
to the point that the electricity fl owing out of the neuron bundles is diminished disease develops.Increasing neurotransmitter levels will effectively increase voltage in the remaining viable neurons
in the bundle, causing electrical fl ow out of the damaged neuron bundles to increase to the point that normal regulation and/or control is once again observed. In this state, from a clinical standpoint, the
symptoms of disease are under control.
<b>Etiology of Bundle Damage</b>
Bundles of monoamine neurons can be impaired from neurotoxin exposures, trauma, or biologicalinsult.56 Neurotoxin exposures are poorly defi ned and ongoing exposures are in contrast to
the MPTP study model of Parkinsonism. The most comprehensive listing located reveals 1179 known neurotoxins.39 Susceptibility of individuals based on genetic predisposition, environmental
infl uences, synergy between chemicals or other predisposing factors suggest that some individuals may experience neurotoxicity from many unlisted substances and at lower than threshold doses
of known neurotoxins, and so was not considered. Under the bundle damage theory it is assumed that neurotoxins are the leading cause of monoamine bundle damage leading to the following
speculation: Depression The bundle damage’s theory of repeated insult during a lifetime can explain the lack of effi cacy seen in the treatment of elderly with reuptake inhibitors who presumably have greater cumulative lifetime
effects from neurotoxins and other events that cause neuron damage. In the end these patients need to have neurotransmitter levels established that are much higher than can be achieved with reuptake
inhibitors alone.With repeated insult more damage occurs, which is cumulative. When the damage is at the point where the neurotransmitter levels needed to control disease symptoms cannot be achieved with the
use of reuptake inhibitors alone, from a clinical standpoint it appears that the drug is not working.This may explain why about 90% of adults treated with reuptake inhibitors achieve results no better
than placebo.The bundle damage theory may also explain why developed countries have a higher rate of depression as the population is exposed at a higher rate to neurotoxins.
Since insult exposure may be ongoing in patients with depression, optimizing nutritional status is important. Improving neuronal ability to minimize and recover from toxic insult form the basis
of the antioxidant nutrients Dr. David Perlmutter explains in Chapter 28, “Parkinson’s Disease,” and the membrane-stabilizing nutrients Dr. Patricia Kane explains in Chapter 24, “Seizures.”
<b> IV. PHARMACOLOGY</b>
AMINO ACIDS
Treatment of depression, as well as any other monoamine neurotransmitter diseases, is not possible through the direct administration of monoamine neurotransmitters. This is due to the fact that monoamine
neurotransmitters do not cross the blood-brain barrier, as depicted in Figure 29.1.2,3,4,5 The only way to increase the levels of central nervous system monoamine neurotransmitter molecules is
to provide amino acid precursors, which cross the blood-brain barrier and are synthesized into their respective neurotransmitters by presynaptic neurons.
REUPTAKE INHIBITOR DEPLETION OF MONOAMINE
The National Institute of Drug Abuse presents a detailed discussion on its website on how reuptake inhibitors deplete neurotransmitters.22 Medicines used to treat depression are not the only drugs
that block reuptake; cocaine and amphetamines block reuptake as well.22 Reuptake inhibitors block
<b>CONCLUSIONS</b>
The bundle damage theory creates a framework by which to offer patients new treatments for clinical depression. The theory underscores the importance of minimizing toxic exposures, through
avoidance where possible, through diminished uptake, and through adequate nutrients. Similarly patients who have inadequate substrate for neurotransmitter synthesis may need cofactors, nutrients
involved in sulfur pathways, and amino acid precursors. Patients may also receive benefi t from amino acid precursors beyond what can be obtained from diet alone.
There are three primary considerations in the use of amino acids for treating depression.First, proper levels of amino acids should be administered with the drugs to prevent depletion of
neurotransmitters. Second, proper use of amino acids will keep the drug functioning properly, avoiding tachyphylaxis. Third, the use of amino acids may cause a drug side effect to become
active. In summary, amino acids hold more therapeutic potential and less potential for harm when
administration is physician-guided.