A New Therapeutic Approach for Treating DEPRESSION. NADH is a safe, potent, biological (natural) ANTIDEPRESSIVE Agent.
Experience with 205 Patients

DISCUSSION
This study confirms and extends our preliminary report on the clinical benefit of NADH for patients suffering from depression ( ⁷ ).

The patients included in our study suffered from depression with various forms of clinical symptoms, in all of which a disturbance in the catechloamines, dopamine, serotonin and norepinphine as well as in the metabolites, vanilin mandelicacid and 5-hydroxyindol-acetic acid levels in blood plasma have been observed (G.D. Birkmayer, unpublished results).

According to the guidelines of the Diagnostic and statistical manual of mental disorder ( ²¹ ) one does not distinguish different forms of depression but only the severity of the symptoms.

NADH seems to be effective with all of them. In order to elucidate the mechanism of NADH action we have to look at the biochemical events leading to depression ( ¹ ). It has been claimed that the balance of neurotransmitters is disturbed and this change is responsible for the clinical symptoms of depression.

One of the approaches in the treatment of depression is the application of monoaminoxidase (MAO) inhibitors, in order to block the metabolic degradation of the catechloamines thus achieving a higher endogenous concentration. Monoaminoxidase inhibitors such as imipramine and amitryptilin as anti-depressive medication( ^{20, 8} ) have been used for more than 30 years. One of the drawbacks of these monoaminoxidase inhibitors is the blockage of the re-uptake of neurotransmitter from the pre-synaptic neuron. Therefore the neurotransmitter accumulate in the synaptic cleft. This unnatural condition causes clinically side-effects. Side effects indicate always over-dosage of the drug. The philosophy of using NADH as anti-depressive substance was its potential capacity to stimulate the endogenous biosynthesis of L-DOPA, dopamine, norepinephrine and other catechloamines, respectively. Previous studies have shown that there is a deficit in the brain of Parkinsonian patients which seems to be responsible for at least some of the symptoms of depression( ^{3, 4} ). As dopamine is synthesized from tyrosine via L-DOPA under the action of tyrosine hydroxylase this particular enzyme plays a central role for biosynthesis of dopamine and noradrenaline ( ¹⁷ ) and due to this also for psychic disorders.

In this context it has been shown that tyrosine-hydroxylase is strongly reduced in Parkinsonian patients, not only in the brain, but also in the adrenal medulla ( ¹⁵ ). This enzyme has 2 cofactors, tetra-hydrobiopterine and iron. Tetra hydrobiopterine was found to be reduced in the brain of Parkinsonian patients by more than 50% yielding a decreased tyrosine-hydroxylase activity ( ¹⁶ ). By stimulating the biosynthesis of tetra hydrobiopterine one may achieve an activation of tyrosine hydroxylase which then leads to a higher dopamine production. Tetra hydrobiopterine is synthesized from dihydropteridine by an enzyme called dihydropteridinreductase ( ²³ ). Cofactor of this enzyme is NADH. The working hypothesis was that addition of NADH will trigger tyrosine-hydroxylase activation and due to this an increase of L-DOPA and dopamine production. In a study with more than 400 patients we have shown that NADH is able to improve the symptoms of Parkinsonian patients ( ⁶ ). Biochemical analysis showed that the improvement of clinical symptoms was paralleled by an increase of the dopamine metabolites HVA and VMA in the urine which provides indirect evidence that NADH is increasing the endogenous dopamine production ( ⁵ ).

Direct support for our hypothesis have been gained from tissue culture experiments. NADH added to the culture medium increased the production of dopamine in phaeochromocytoma cells up to 6 times. Furthermore, tyrosine hydroxylase activity was stimulated by NADH to 175% ( ²¹ ).

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