Process and composition for treating disorders by administering lecithin

Lecithin without a drug is administered to a patient in order to increase acetylcholine levels in the brain or other tissues, thereby to alleviate the effects of tardive dykinesia, manic-depressive disease, memory impairment or familial ataxias.

BACKGROUND OF THE INVENTION 
This invention relates to a process for the administration of lecithin in 
the absence of a drug in order to treat human disorders by increasing 
acetylcholine levels in brain and other tissues. 
There are a number of diseases which affect acetylcholine-containing 
neurons in the brain or other tissues, and which are treated by drugs that 
cause undesired side effects by diminishing acetylcholine's release; there 
also exists diseases now treated by other drugs in which the potency 
and/or efficacy of the drugs could be improved by combining them with 
choline or natural or synthetic compounds that dissociate to form choline 
in order thereby to enhance the release of acetylcholine. Such diseases 
include both those primarily involving the brain (e.g., diseases of higher 
cortical functions; psychiatric illnesses; movement disorders) and those 
involving the peripheral nervous system (e.g., neuromuscular disorders). 
Tardive dyskinesia is a particularly common movement disorder associated 
with inadequate release of brain acetylcholine as a result of drug 
administrations for the initial brain disease (e.g., psychosis). Tardive 
dyskinesia is a choreic movement disorder characterized by involuntary 
twitches in the tongue, lips, jaw and extremities. It typically occurs in 
susceptible persons after chronic ingestion of neuroleptic drugs and may 
involve an imbalance in the postulated reciprocal relation between 
dopaminergic and cholinergic neurons in the basal ganglions. Thus, drugs 
that either block catecholamine synthesis (e.g., 
alpha-methyl-p-tyrosines), deplete the brain of monoamines (e.g., 
reserpine, tetrabenazine) or antagonize dopamine's actions on synaptic 
receptors (e.g., pherothiazines, galoperidol) often suppress tardive 
dyskinesia, whereas drugs that indirectly stimulate dopamine receptors 
(e.g., amphetamine, levodopa) often exacerbate the abnormal movements. 
Drugs assumed to increase the amount of acetylcholine within brain 
synapses (e.g., physostigimine, deanol), also tend to suppress the chorea 
of tardive dyskinesia, whereas anticholinergics (e.g., scopolamine), make 
it worse. 
We have shown that choline administered by injection or by dietary 
supplementation increases blood choline levels in the rat; this, in turn, 
increases choline levels in cholinergic neurons within the brain and 
elsewhere in the body, thereby accelerating the synthesis of 
acetylcholine, increasing tissue acetylcholine levels, and increasing the 
amounts of acetylcholine released into brain synapses. In human beings, 
oral doses of choline or of lecithin, a naturally-occurring compound that 
dissociates to choline were found to cause dose-related increases in blood 
choline levels of sufficient magnitude (based on the studies on rats) to 
enhance brain acetylcholine synthesis and release; choline levels in the 
cerebrospinal fluid also rose in parallel. It has also been reported in 
four human patients that the administration of choline decreased the 
choreiform movements of tardive dyskinesia; no data were provided as to 
whether or not the drug given concurrently for psychosis (haloperidol, 3 
mg per day) continued to be effective during the brief period of choline 
administration, and it was concluded that the apparent effectiveness of 
choline had to be interpreted with caution, since " . . . all four 
patients with tardive dyskinesia could have been gradually improving 
during the study" since this disease is characterized by extreme 
variability of clinical course. Thus, prior to our invention, disclosed in 
Ser. No. 847,967, filed Nov. 2, 1977, it had not been known that the 
concomitant administration of choline or of a natural or synthetic 
compound that dissociates to form choline along with an anti-psychotic 
drug that causes tardive dyskinesia as a side effect could significantly 
reduce or prevent the onset of tardive dyskinesia, without blocking the 
effectiveness of the drug in treating psychosis. 
It would be desirable to eliminate the use of drugs in certain patients 
being treated for psychiatric disease, memory impairment or other brain 
dysfunctions in order to eliminate undesirable side effects of the drugs. 
Furthermore, it would be desirable to replace choline as an oral source of 
precursor for brain acetylcholine since the administration of choline is 
accompanied by undesirable odor. 
SUMMARY OF THE INVENTION 
This invention is based upon the discovery that lecithin, when administered 
alone, optimizes physiological functions and restores impaired 
physiological functions in situations associated with inadequate 
cholinergic transmission such as tardive dyskinesia, manic-depressive 
states or other psychiatric diseases, memory impairment, familial ataxias 
or the like. The lecithin can be administered orally such as in tablet, 
capsule, granules or liquid form or parenterally by intravenous, 
intramuscular or subcutaneous injection.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS 
In accordance with this invention, lecithin is administered to a patient 
without a drug in order to increase blood levels of choline, and thereby 
to increase the level of acetylcholine in the brain. The acetylcholine is 
synthesized from choline and acetyl CoA in a reaction catalyzed by choline 
acetyltransterase (CAT). It has been found that the administration of 
lecithin alone is useful for the treatment of physiological functions 
associated with inadequate cholinergic transmission. 
There are a number of brain and peripheral diseases involving cholinergic 
neurons that are presently treated with drugs that are only sometimes 
effective, or that require very large doses of the drugs (with 
correspondingly greater cost and incidence of side effects); some of these 
diseases can be effectively treated by replacing the existing drug therapy 
with the administration of lecithin. One example is the mania phases of 
manic-depressive psychosis, which is currently treated with lithium salts. 
These salts, as a side effect, can cause toxic changes in the kidneys. The 
administration of lecithin would allow for effective treatment of the 
mania without the lithium dose. Another example is memory impairment 
occurring in apparently normal people or those associated with aging or 
with neurological diseases. There is no adequate current mode of 
treatment. In addition, lecithin alone may be used to treat patients with 
familial ataxia, another degenerative disease for which there is no 
adequate treatment. 
The lecithin can be administered as lecithin with either saturated or 
unsaturated fatty acid side chains. The lecithin is administered so that a 
choline level of at least about 10-25 nanomoles/ml and usually between 
about 10 and 50 n moles/ml is attained in the patient's blood stream. When 
utilizing lecithin in a liquid carrier, it is administered in amounts of 
between about 0.1 and 100 g/day. When lecithin is administered in granular 
form, as a tablet or in a capsule, it is employed in amounts of between 
about 0.1 and 100 g/day, usually between about 30 and 50 g/day. Normally, 
lecithin is not available as a pure compound and is available in admixture 
with other phospholipids wherein the lecithin comprises about 20-30 weight 
percent of the mixture. 
The following example illustrates the present invention and is not intended 
to limit the same. 
EXAMPLE I 
This example illustrates that lecithin significantly improves memory loss 
in a normal patient. 
A patient who was not taking medication, but who had suffered memory loss, 
but who did not suffer from any other brain dysfunction or from any 
psychiatric disease was treated with lecithin. Prior to the lecithin 
treatment, he was tested for memory quotient and intelligence quotient by 
the Wechsler Memory & Intelligence tests; his memory quotient was 122. 
Lecithin obtained from the Nattermann Corporation and which comprises 80% 
lecithin was orally administered to the subject at a dosage of 10 g. every 
8 hours over a period of 6 weeks. The dosages were prepared by mixing the 
lecithin in foods. 
Blood samples for choline measurements were collected from the subject 
before the lecithin trial began and 6 weeks later during lecithin 
ingestion; plasma samples were separated, frozen and assayed for choline 
content by a conventional radioenzymatic method. 
Before treatment, plasma choline levels were 12. g.+-.1.1 nmol per 
milliliter. After lecithin ingestion, plasma choline levels in blood 
obtained 4 hours after a lecithin dose increased to 30.3.+-.2.7 nmol per 
milliliter (P&lt;0.01). During the 6th week of lecithin ingestion at a time 
the plasma choline level was significantly elevated, his memory quotient 
improved to 140.