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WO1999024040A1 - Stimulation de la production d'hormones - Google Patents

Stimulation de la production d'hormones Download PDF

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Publication number
WO1999024040A1
WO1999024040A1 PCT/US1998/023552 US9823552W WO9924040A1 WO 1999024040 A1 WO1999024040 A1 WO 1999024040A1 US 9823552 W US9823552 W US 9823552W WO 9924040 A1 WO9924040 A1 WO 9924040A1
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Prior art keywords
precursor
neurotransmitter
hormone
composition
regulatory
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PCT/US1998/023552
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English (en)
Inventor
William E. Shell
Mark E. Jarmel
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Nutracorp Scientific, Inc.
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Application filed by Nutracorp Scientific, Inc. filed Critical Nutracorp Scientific, Inc.
Priority to AU13818/99A priority Critical patent/AU1381899A/en
Publication of WO1999024040A1 publication Critical patent/WO1999024040A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients

Definitions

  • This invention relates to agents for promoting production of hormones within the body. Insufficient synthesis of one or more hormones occurs not only due to hereditary conditions, various disease states and other etiologies, but simply with advancing age in the normal aging process. Senescence of the male neuroendocrine system is associated with decreased levels of testosterone. In men, age-related decline in testosterone levels is associated with conditions such as a loss of vitality, diminished immune function, decreased upper body lean muscle mass, decreased libido, and increased incidence of erectile dysfunction, osteoporosis and diabetes. Senescence of the female neuroendocrine system is associated with decreased levels of estrogens, progesterone, and testosterone. Menopause-associated changes in the neuroendocrine system may result in conditions such as diminished immune function, decreased libido, and increased incidence of osteoporosis and cardiovascular disease.
  • Bromocriptine is a synthetic dopamine agonist that is utilized to reduce elevated prolactin levels. Synthetic forms of testosterone are administered in order to raise decreased testosterone levels. In women, exogenous forms of estrogen or other steroid hormones are administered in order to treat undesirable conditions associated with menopause.
  • Each of these pharmaceutical therapies has undesirable side effects and require physician visits. Thus, there exists a need for non-drug dietary supplements that can promote synthesis of hormones within the body, have reduced risk of side effects, and do not require physician visits.
  • the steroid hormones progesterone, estrogen and testosterone are synthesized from a class of endogenous precursors comprised of pregnenolone, dehydroepialdosterone (DHEA), and androstenedione. Androstenedione is the immediate precursor utilized in the synthesis of testosterone. Additionally in women, androstenedione is the immediate precursor utilized in the synthesis of estrogens and is know to promote the synthesis of progesterone. Androstenedione may be synthesized in the body by conversion from pregnenolone, progesterone, or DHEA.
  • pregnenolone, DHEA and androstenedione are produced in the adrenal glands, thymus, and pancreas.
  • the mineralocorticoids, and particularly the steroid hormone aldosterone, and the glucocorticoids, particularly the steroid hormone cortisol, are synthesized in the adrenal glands from the endogenous precursor pregnenolone.
  • pregnenolone, DHEA and androstenedione are found in the organ meats known as "sweet breads" that have long been utilized as foodstuffs, pregnenolone, DHEA and androstenedione may be administered without a prescription as dietary supplements in compliance with regulatory guidelines. Accordingly, procedures to utilize these precursors that would be effective in the treatment of hormone insufficiency would be highly desirable.
  • This invention has the object of effectively promoting synthesis of hormones. It is known that certain neurotransmitters regulate the synthesis and secretion of specific hormones.
  • the invention promotes hormone synthesis by concomitantly administering a hormone precursor with a precursor for a neurotransmitter that stimulates synthesis of the targeted hormone.
  • This invention provides methods and compositions for promoting the synthesis and secretion of endogenous hormones. These embodiments are based upon the discovery that precursors for hormone regulatory neurotransmitters will act synergistically with precursors for the particular hormones which they regulate, thereby to promote glandular secretion of those hormones.
  • This invention utilizes the natural precursors for targeted hormones and the natural precursors for neurotransmitters, rather than the hormones themselves, natural or synthetic, or other prescription drugs. It is also an object to promote optimal production of such hormones by a method that utilizes the natural self-regulatory mechanisms of the body.
  • the neurotransmitter precursors and hormone precursors utilized in this invention are substances normally assimilated and processed by the body's intrinsic homeostatic mechanisms. Thus, administering precursors normally utilized by the body's synthesizing mechanisms reduces the possibility of side effects.
  • This invention is applicable to both steroidal and non-steroidal hormones, and in the case of steroidal hormones including the sex hormones testosterone, the estrogens, particularly estradiol, and progesterone, the glucocorticoids, and specifically cortisol, and the mineralocorticoids, and specifically aldosterone.
  • steroidal hormones include triiodothyronine and thyroxin.
  • the endocrine-regulating neurotransmitter norepinephrine stimulates synthesis of testosterone.
  • a precursor for norepinephrine is administered concomitantly with a precursor for testosterone.
  • the amino acids tyrosine and phenylalanine are precursors for norepinephrine.
  • the precursors for testosterone include androstenedione, DHEA and pregnenolone.
  • Histidine is the precursor for the neurotransmitter histamine, which inhibits release of dopamine and stimulates norepinephrine release.
  • histamine promotes conversion of catecholamine precursors into norepinephrine as opposed to dopamine.
  • Norepinephrine regulates progesterone secretion by inhibiting its synthesis. Synthesis of estrogens is promoted by norepinephrine' s inhibition of progesterone secretion, combined with dopamine' s stimulation of estradiol secretion, (Bodis J, Tinneberg HR, Torok A, Cledon P, Hanf V, Papenfuss F: Effect of noradrenaline and dopamine on progesterone and estradiol secretion of human granulosa cells. Acta Endocrinol (Copenh) 1993;129:165-168).
  • precursors for neurotransmitters that stimulate synthesis of estrogens include, tyrosine and phenylalanine for norepinephrine and dopamine, histidine for histamine, and glutamic acid and glutamine for GABA.
  • the precursors for estrogens include androstenedione, pregnenolone and DHEA.
  • Precursors for norepinephrine, dopamine, histamine and /or GABA are administered concomitantly with a precursor for estrogens to enhance the secretion of estrone, estradiol and/ or estriol.
  • neurotransmitter precursors for neurotransmitters that stimulate its synthesis dopamine, serotonin, histamine, GABA, acetylcholine and /or glutamate are administered concomitantly with a precursor for progesterone.
  • the neurotransmitter precursors include, tyrosine and phenylalanine for dopamine, tryptophan or 5-hydroxytryptophan for serotonin, histidine for histamine, glutamic acid and glutamine for GABA and glutamate, and choline, phosphatidyl choline or lecithin for acetylcholine.
  • one or both of their common precursors, progesterone and pregnenolone are administered concomitantly with a precursor of a regulatory neurotransmitter that stimulates their production, including precursors for the neurotransmitters norepenephrine, serotonin, histamine and /or acetylcholine.
  • the neurotransmitter precursors include tyrosine and phenylalanine for norepenephrine, tryptophan or 5- hydroxytryptophan for serotonin, histidine for histamine and choline, phosphatidyl choline or lecithin for acetylcholine.
  • the precursors for these hormones, iodine in elemental or salt form and either tyrosine or phenylalanine are administered concomitantly.
  • tyrosine and phenylalanine also serve as precursors for the neurotransmitter norepinephrine, which stimulates thyroid hormone synthesis.
  • compositions of this invention are employed both for relieving deficiencies of the hormones due to senescence, diseases, genetic disorders and other conditions and for generally optimizing their secretion in maintenance of good health.
  • one or more xanthines and particularly theobromine is administered along with the hormone and neurotransmitter precursors to enhance the release of the neurotransmitter and thereby potentiate the release of the hormone.
  • histidine, aspartic acid, glutamine, and /or glutamic acid is administered along with the hormone and neurotransmitter precursors.
  • These amino acids form a class of precursors for neurotransmitters that depolarize neurons that release other neurotransmitters.
  • One or more of these precursors for depolarizing neurotransmitters may be utilized to enhance the release of a targeted neurotransmitter and thereby potentiate the release of the hormone.
  • xanthines and a precursor for a depolarizing neurotransmitter are employed together with the hormone precursor and the regulating neurotransmitter precursor for a further enhanced effect as they operate through different mechanisms to enhance neurotransmitter release and are thus complementary.
  • the single dosage forms for oral administration constitute pills, caplets, chewable wafers and other forms individualized for administering the appropriate single dose quantities of the selected constituents.
  • hormone precursors and precursors of regulatory neurotransmitters that stimulate secretion of the hormone are administered concomitantly to enhance hormone secretion for the purpose of ameliorating hormone deficiency and thereby optimizing the hormone function.
  • Hormone deficiency includes any condition in which secretion of the hormone is less than optimal. It may constitute a general deficiency such as in senescence or other glandular impairment or insufficiency. Hormone deficiency results in less than optimal regulation of body functions leading to a wide variety of conditions and disorders. These are the conditions and disorders that may be treated utilizing this invention.
  • a precursor for that hormone is administered along with a precursor of a specific regulatory neurotransmitter that enhances the secretion of that hormone. While the same neurotransmitter may enhance the secretion of more than one hormone, each is specific in its effect. Hence, the neurotransmitters precursors for use in enhancing secretion of a particular hormone are chosen accordingly.
  • steroidal hormones form an important class, and particularly the sex hormones testosterone, the estrogens, particularly estradiol, and progesterone, the glucocorticoids, and specifically cortisol, and the mineralocorticoids, and specifically aldosterone.
  • the precursors for norepinephrine are effective together with the hormone precursors for testosterone, androstenedione, DHEA or pregnenolone, to enhance its secretion.
  • the precursors for dopamine, histamine and GABA may be employed along with a precursor for estrogens chosen from pregnenolone, androstenedione and DHEA.
  • Tyrosine or its precursors, such as phenylalanine is employed as the precursor for dopamine, histidine for histamine and glutamic acid or glutamine for GABA.
  • Pregnenolone the precursor for the hormone progesterone, is employed to enhance its secretion, together with tyrosine and /or phenylalanine as a precursor for dopamine, 5-hydroxytryptophan and tryptophan as precursors for serotonin, histidine as a precursor for histamine, glutamic acid and glutamine, as a precursor for GABA and glutamate and/ or choline, phosphatidyl choline or lecithin as a precursor for acetylcholine. Additionally, a precursor may be employed for the acetyl group of acetylcholine, including pyruvates, carnitine, acetyl-L-carnitine.
  • one or both of their precursor, progesterone and pregnenolone are administered together with tyrosine and phenylalanine, precursors for norepenephrine, tryptophan or 5-hydroxytry ⁇ tophan as precursors for serotonin, histidine the precursor for histamine and/ or choline, phosphatidyl choline or lecithin, precursors for acetylcholine.
  • iodine In the case of non-steroidal hormones, to enhance the secretion of the hormones triiodothyronine and thyroxin, their precursors, iodine, and either tyrosine or phenylalanine are administered concomitantly.
  • the tyrosine or phenylalanine serve as well to enhance secretion of these hormones by acting also as precursors for norepinephrine.
  • the iodine may be administered in elemental form or as a non-toxic salt, preferably a soluble salt such as sodium iodide.
  • Tyrosine and its precursors, including phenylalanine are precursors for both dopamine and norepinephrine and will enhance the production of both.
  • Dopamine may decrease the effectiveness of the norepinephrine so where norepinephrene is the desired neurotransmitter to enhance secretion of the hormone, it can be advantageous to administer histidine, as a precursor for histamine, along with the tyrosine or phenylalanine, as histamine will inhibit release of dopamine.
  • glutamic acid and glutamine are also precursors for glutamate and glutamate can decrease the effectiveness of GABA. Therefore, where GABA is desired for enhancing hormone secretion, it may be advantageous to also administer along with the glutamic acid a glutamate inhibitor to minimize glutamate release, in favor of GABA.
  • Glutamate inhibitors include proline, either as the free acid, pharmaceutially accept salts thereof and hydrates and acid adducts thereof.
  • Pharmaceutically acceptable magnesium salts, particularly water soluble salts such as magnesium chloride may also be employed. The latter may be advantageously administered chelated with an amino acid.
  • the hormone precursors may be employed in this invention in pure form, synthesized or derived from animal or other sources.
  • the neurotransmitter precursors may also be employed in this invention in pure form, e.g. exogenous material synthesized or derived from animal or vegetable protein, particularly purified extracts isolated from the amino acid residues in enzyme hydrolyzed proteins.
  • the neurotransmitter and hormone precursors may also be in the form of their pharmaceutically acceptable derivitives, including their salts, hydrates, acid adducts (e.g. hydrochloric acid) and mineral chelates (e.g. salts bound to the precursor by chelation bonding).
  • derivitives include, in the case of acetylcholine, choline sources such as phosphatidylcholine, cytidyldiphospo choline and glycerophosphocholine.
  • a tryptophan source particularly useful in this invention both because it is a natural food source and because of regulatory restrictions, is naturally occurring protein. Proteins may either be enzyme hydrolyzed prior to administration to release tryptophan, or unhydrolyzed protein may be administered along with a proteolytic enzyme that will liberate tryptophan in the gastrointestinal tract. Commercial preparations of predigested proteins typically from milk-derived protein, such as casein or whey, are available and may be administered in composition with histidine and /or a xanthine.
  • the tryptophan is to be administered in the form of a predigested protein or a protein to be enzyme hydrolyzed upon administration, it is important in this invention to administer the protein concomitantly with a carbohydrate.
  • Concomitant administration of a carbohydrate and particularly sugar, dextrins, starch and the like, is desired in order to cause release of insulin to remove from the bloodstream the other amino acids competing with tryptophan for transport across the blood-brain barrier.
  • soluble proteins such as albumin are preferred, for ease of breakdown. Whey, casein and soy are convenient protein sources.
  • Proteolytic enzymes may include papain, chymopapain, bromelain, trypsin, and pepsin.
  • Xanthines and precursors for a depolarizing neurotransmitter selected from histamine, glutamate, and aspartate may be administered either separately or, most advantageously, together, along with neurotransmitter precursors and the hormone precursors to potentiate the release of the precursors' respective neurotransmitters and thereby further enhance the secretion of hormone, as will be described. It is a highly advantageous feature of this invention to utilize the xanthines and the precursors for depolarizing neurotransmitters together, as they operate by different mechanisms to have a multiplier effect in potentiating hormone secretion.
  • Xanthines constitute a class of non-selective adenosine antagonists and they include theobromine, caffeine and theophylline. They are capable of promoting release of the neurotransmitters serotonin, dopamine, norepinephrine, histamine, acetylcholine, glutamate, and aspartate. Xanthines administered in accordance with this invention potentiate neurotransmitter synthesis and release for each of serotonin, dopamine, norepinephrine, acetylcholine, glutamate, and aspartate. Combining one or more xanthines, with one or more neurotransmitter precursors, allows the desired effects to be achieved with reduced, safe, doses of the individual agents.
  • the xanthines may be used in the form of their free compounds or as their salts, adducts or other derivatives, for example citrated caffeine, theophylline ethylenediamine, theophylline sodium acetate, sodium glycinate, the choline salt, the theophylline derivatives theophylline megumine and dyphylline, theobromine calcium salicylate, sodium acetate or sodium salicylate.
  • a particularly suitable form of xanthines for use in this invention are those that are derived from natural sources. Cocoa provides a unique combination of the xanthines theobromine and caffeine in a form that is normally easily ingested and tolerated by the subject. Cocoa powder was originally included in preliminary formulations with neurotransmitter precursors to improve flavor and because its mood enhancing effects have appealed to people for centuries. An unexpected result was that the cocoa powder significantly potentiated the effects of the neurotransmitter precursors. This potentiating effect was determined by us to be produced by the naturally occurring xanthines present in cocoa powder.
  • Infusions of caffeine from coffee beans and of caffeine and theophylline from tea leaves may be employed as a natural source of these xanthines, either in liquid form as coffee and tea, or in dried extract form, alone or, more conveniently, in composition with the neurotransmitter precursor.
  • Caffeinated soft drinks, chocolate, guarana, ephedra, mate' and other food or herb sources may be employed.
  • each hormone precursor used in accordance with this invention is in an amount sufficient to enhance synthesis and release of its respective hormone in combined administration with the neurotransmitter precursors employed as potentiated by xanthines and /or precursors for depolarizing neurotransmitters, if they are employed as well.
  • the desirable dosage range for all of the precursors for testosterone, estrogens, progesterone, aldosterone and cortisol is between 1 and 1,000 mg and preferably each is given as a single dose in the amount of between 10 and 500 mg.
  • the dosage of iodine used as a precursor for thyroid hormones is 5 to 50 mg, expressed as elemental iodine, either in the form of elemental iodine or iodine salts.
  • the dosage of tyrosine or phenylalanine as both a neurotransmitter precursor and a hormone precursor for thyroid hormones is desirably between 10 and 1,000 mg and preferably within the range of 50 and 750 mg.
  • each regulatory neurotransmitter precursor used to enhance hormone secretion is an amount sufficient to enhance synthesis and release of its respective neurotransmitter both where it is administered alone or in combined administration with a depolarizing neurotransmitter precursor and/ or the xanthines.
  • an effect may result in some cases from a dosage of all of the regulatory and depolarizer neuotransmitter precursors as low as 1 mg.
  • a dosage for each of the precursors of at least 10 mg., and preferably 50 mg. or higher is advisable for a practical enhancement.
  • the usual range of administration in practice is desirably between 100 mg. to 750 mg. per dose.
  • the maximum practical dose is about 1,000, although essentially for all precursors but much higher doses may be feasible, even up to 3 grams or higher, without undue risk of side effects.
  • 5- hydroxy tryptophan and tryptophan Special considerations may be appropriate for 5- hydroxy tryptophan and tryptophan, in view of safety considerations as to contaminants. In view of regulatory restrictions in this respect. Thus for 5-hydroxytryptophan or tryptophan a single dose range from about 2.5 to 100 milligrams, with a typical dose of 45 milligrams, may be desirable.
  • each neurotransmitter precursor is applicable for each hormone with which it is indicated above to be effective and for each indicated hormone precursor therefor.
  • the ranges also apply to combined administration of the precursor with histidine and /or another depolarizing neurotransmitter precursor, with a xanthine, or with both.
  • hydrolyzed proteins or proteins to be hydrolyzed in the gastrointestinal tract are employed as the source of tryptophan, the proteins should be in an amount to provide the tryptophan dosage levels of this invention as discussed above. Typically, this will be in a range of between around one half of a gram and 30 gm. The amount of enzyme employed may be 30 to 50 mg. per gram of protein. Insulin producing carbohydrates administered with the protein are desirably at dosage levels of from about one half gram to 5 grams. Hydrolyzed protein sources of tryptophan may be taken separately in tablet form, utilizing commercially available predigested protein tablets, such as LLP Concentrated Predigested Protein sold by Twin Laboratories, Inc., Ronkonkoma, New York containing approximately 18 mg. of tryptophan per 1 gram tablet
  • Xanthines are employed in this invention in dosage ranges appropriate to promote release of neurotransmitters and to avoid undesired side effects.
  • Theobromine may be administered in a dosage of from 1 mg. to 2 grams or higher.
  • Caffeine may be administered in a dose of from 1 to 200 mg or higher if tolerated by the subject.
  • Theophylline may be administered in a dose of from 1 to 200 mg. or higher if tolerated by the subject. Cocoa may be administered in a dose of 1 mg. to 10 grams or higher for an appropriate dose of xanthines, with a preferred dose being 500 to 800 milligrams. Xanthine-containing beverages such as tea or coffee may be employed, with one to two cups providing an appropriate dose. Somewhat higher doses of these xanthines may be employed with some subjects without undue discomfort.
  • the dosage of a precursor for a depolarizing neurotransmitter for use with other precursors in order to additionally enhance the effect of their associated neurotransmitters is an amount sufficient to enhance brain synthesis and release of the depolarizing neurotransmitter, and to enhance thereby the synthesis of other neurotransmitters for which precursors are concomitantly administered, including one or more of the neurotransmitters serotonin, dopamine, norepinephrine, acetylcholine, GABA and glutamate.
  • the dosage ranges for these precursors is the same as that for their use as regulatory neurotransmitters, as discussed above.
  • the desired single dose is typically from about 1 to 500 milligrams and may be up to 1,000 milligrams, with a typical dose being 30 to 200 milligrams.
  • the precursor for the depolarizing neurotransmitter aspartate the desired dosage range is from about 1 to 1,000 milligrams, with a typical dose of 300 to 600 milligrams.
  • the desired dosage is the same as the same as described above for their use in this invention as precursors for the regulatory neurotransmitter glutamate or GABA.
  • the regulatory neurotransmitter precursor used for the target hormone is a precursor for glutamate or GABA
  • a precursor of another depolarizing neurotransmitter i.e. a precursor for either histamine or aspartate.
  • the neurotransmitter precursors, hormone precursors and xanthines of this invention may be administered orally separately, or for assurance of appropriate proportions and dosages as well as for convenience, they are administered together in the same composition.
  • the dosage forms for administration separately or in the same composition may be any of the conventional forms, including capsules, caplets, chewable wafers, tablets, liquid suspensions, powders and the like.
  • Xanthine dosages may take the form of chocolate preparations, cocoa drinks, infusions, e.g. coffee and tea and cola drinks containing caffeine.
  • compositions in the form of powders or liquids may be packaged in multiple dosage quantities with instructions to the user to extract therefrom for ingestion appropriate individual dosage amounts, e.g. a teaspoonful.
  • appropriate individual dosage amounts e.g. a teaspoonful.
  • the compositions are desirably prepared in discreet units, e.g. capsules, wafers, etc., which each contain the appropriate dosage amounts of neurotransmitter precursors with xanthines and /or histidine, for a single dose as discussed above.
  • compositions may include the usual carriers, fillers, excipients, flavorings and adjuvants in addition to neurotransmitter precursors, hormone precursors and the potentiating agents contained in cocoa.
  • they may also include folic acid and vitamin B6 to enhance conversion of tyrosine to dopamine and norepinephrine, and histidine to histamine respectively.
  • the preferred amount of folic add is 200 meg. per dose with a range of 1 to 800 meg. /dose.
  • the preferred amount of vitamin B6 is 20 mg. with a range of 1 to 100 mg./ dose.
  • the dosages when the subject has an empty stomach, typically at least an hour after the subject has eaten.
  • Administering the compositions on an empty stomach is important in order to avoid undesirably slow uptake of precursors into the bloodstream. Uptake of administered neurotransmitter precursors across the blood-brain barrier would be particularly inhibited by competition for absorption by other amino acids from the ingested food.
  • the precursors of this invention are administered as a single dose per day but they may given more frequently, twice a day or in some instances three times daily.
  • This example illustrates the use of the testosterone precursor and in combination with precursor for the neurotransmitter norepinephrine to promote to promote testosterone secretion in men.
  • Norepinephrine enhances testosterone synthesis.
  • a formulation was prepared comprising tyrosine 500 mg, androstenedione 50 mg, histidine 200 mg, cocoa 500 mg, sugar 1,000 mg, vitamin B6 10 mg, and folic add 0.2 mg. This formulation is best administered once or twice daily on an empty stomach, at least one or two hours after eating.
  • This product was prepared in the form of a blended powder, portioned into individual doses and administered to three male subjects ages 45, 46 and 53.
  • the product may alternatively be prepared in the form of a chewable wafer sized to contain the same dose, by combining with the blended powder a sweetener and excipients.
  • Phenylalanine can be substituted for tyrosine in this formulation, in the same quantity, if desired.
  • DHEA or pregnenolone can be substituted for androstenedione, utilizing the same quantity, although they are not preferred because partial conversion to estrogen or progesterone may possibly occur.
  • the example illustrates a formulation for administration to perimenopausal or postmenopausal women in order to promote synthesis of testosterone and estrogens, primarily estradiol.
  • Androstenedione is the primary precursor utilized in women to synthesize both estrogens and testosterone. Since dopamine promotes estrogens and norepinephrene promotes testosterone synthesis, tyrosine the precursor for both norepinephrine and dopamine is employed in this formulation to enhance production of both neurotransmitters in order to enhance secretion of both estrogens and testosterone.
  • a formulation is prepared comprising 500 mg tyrosine, 50 mg androstenedione 400 mg cocoa and 1,000 mg of sugar.
  • the cocoa contains primarily theobromine as a xanthine to potentiate release of the neurotransmitters.
  • DHEA in the amount of 25 to 50 mg may be added as another precursor for estrogens and testosterone to further enhance synthesis and secretion thereof.
  • This single dose formulation is best administered once or twice daily on an empty stomach, at least one or two hours after eating.
  • This example illustrates a formulation that may desirably be administered in postmenopausal women in order to promote endogenous synthesis of progesterone, utilizing the precursor for progesterone, pregnenolone.
  • Acetylcholine promotes the synthesis of progesterone from pregnenolone, so its precursor, choline, is utilized in this formulation to enhance progesterone secretion.
  • Addition of DHEA shifts synthesis in the direction of progesterone.
  • a formulation is prepared comprising tyrosine 500 mg, pregnenolone 30 mg, DHEA 25 mg, choline 200 mg, cocoa 400 mg, and sugar 1,000 mg.
  • lecithin in an amount between 200 mg and 1,000 mg, may be substituted for choline as a precursor for acetylcholine.
  • histidine, tryptophan, GABA, glutamine and /or glutamic add may be added to this formulation to augment progesterone synthesis or in full substitution for the tyrosine.
  • histidine, glutamine and /or glutamic add is used to augment the tyrosine, their neurotransmitters additionally ad as depolarizers thereby further enhancing release of dopamine and hence promoting progesterone production.
  • This single dose formulation is best administered once or twice daily on an empty stomach, at least one or two hours after eating.
  • This example illustrates a formulation that may desirably be administered in postmenopausal women in order to promote endogenous synthesis of dopamine, estrogen and testosterone.
  • a formulation may be prepared comprising tyrosine 500 mg., androstenedione 50 mg., pregnenolone 30 mg., DHEA 25 mg., cocoa 400 mg., and sugar 1,200 mg. This formulation is best administered, as a single dose, as in Example 1.
  • This example illustrates the use of glutamine and androstenedione to promote the synthesis and release of the neurotransmitter GABA and testosterone.
  • This formulation may be administered to enhance sexual receptivity in women.
  • Proline is concomitantly administered with the glutamine to promote the desired GABA activity in the brain while inhibiting glutamate activity.
  • a formulation may be prepared comprising tyrosine 300 mg., glutamine 500 mg,, proline 500 mg dressing androstenedione 50 mg tone cocoa 400 mg busy and sugar 1,200 mg.
  • This single dose formulation is best administered as in Example 1.
  • This product was prepared in bulk in the form of a blended powder in the proportions indicated and then portioned into individual doses each containing the above amounts..
  • glutamic add may be substituted in like amount for the glutamine in this formulation.
  • glutamine is preferred due to its greater uptake across the blood-brain barrier.
  • This example illustrates a formulation for the purpose of increasing the production of cortisol.
  • This formulation may be used in the treatment of inflammatory conditions and other indications for which glucocorticoids are useful.
  • a single dose formulation may be prepared by comprising tyrosine 500 mg, pregnenolone 60 mg, histidine 200 mg. and caffeine 50 mg by blending ingredients as powders. This formulation is best administered as in Example 1.
  • This example illustrates a formulation for the purpose of increasing the production of aldosterone.
  • This formulation may be used in the treatment of hypertension and other indications for which mineralocorticoids are useful.
  • a single dose formulation may be prepared by comprising tryptophan 70 mg, pregnenolone 60 mg, histidine 200 mg. and caffeine 50 mg by blending ingredients as powders. This formulation is best administered as in Example 1
  • This example illustrates the use of a neurotransmitter precursor together with a hormone precursor to enhance the synthesis and secretion of thyroid hormones.
  • Tyrosine and iodine are both utilized by the body as precursors for thyroid hormones.
  • tyrosine is the precursor for the neurotransmitter norepinephrine, which further promotes thyroid activity.
  • a formulation may be prepared comprising tyrosine 500 mg., iodine 15 mg., histidine 100 mg. and sugar 1,200 mg. This formulation is best administered as in Example 1 in the treatment of hypothyroidism, given as a single daily dose or more frequently as indicated.
  • the synergistic combinations of the invention allow reduced doses of the individual components, particularly of the neurotransmitter precursors, to be used to achieve the desired effects.
  • the reduced doses decrease side effects caused by pharmaceutical agents heretofore necessary to achieve the desired effects.
  • Our invention allows enhanced functioning of the neuroendocrine-reproductive-immune network to be achieved without utilizing pharmaceuticals.
  • Our invention allows these desired effects to be achieved at dosage levels of neurotransmitter and hormone precursors that are considered safe by regulatory authorities. Previous attempts to use certain of the components in isolation were either ineffective or required dosages which caused side effects.

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Abstract

La présente invention concerne des procédés et des compositions permettant de renforcer la production d'hormones, et partant de remédier partiellement à la déficience hormonale d'un sujet. Le procédé consiste à administrer par voie orale des précurseurs de l'hormone à stimuler et de l'accompagner d'un précurseur d'un neurotransmetteur régulateur qui renforce la production de l'hormone. Pour renforcer encore plus la production hormonale, on administre un complément de xanthine venant favoriser la libération du neurotransmetteur régulateur. En outre, on administre un complément de précurseurs permettant la dépolarisation des neurotransmetteurs que sont l'histamine, la glutamine et l'aspartate, et ce, afin de favoriser plus encore la libération du neurotransmetteur régulateur.
PCT/US1998/023552 1997-11-06 1998-11-05 Stimulation de la production d'hormones WO1999024040A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1146878A1 (fr) * 1998-02-26 2001-10-24 Timothy Cochran Compositions biochimiques utilisees dans des traitements pour l'homme
EP1996213A4 (fr) * 2006-03-22 2014-08-20 Targeted Medical Pharma Inc Procédé et compositions pour potentialiser des médicaments à l'aide d'aliments thérapeutiques à base d'acides aminés

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US5208225A (en) * 1986-02-27 1993-05-04 Warner-Lambert Company Compositions containing fixed combinations
US5407913A (en) * 1992-12-03 1995-04-18 Celtrix Pharmaceuticals, Inc. Method and composition for systemic treatment of tissue injury
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* Cited by examiner, † Cited by third party
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EP1146878A1 (fr) * 1998-02-26 2001-10-24 Timothy Cochran Compositions biochimiques utilisees dans des traitements pour l'homme
EP1146878A4 (fr) * 1998-02-26 2002-12-04 Timothy Cochran Compositions biochimiques utilisees dans des traitements pour l'homme
EP1996213A4 (fr) * 2006-03-22 2014-08-20 Targeted Medical Pharma Inc Procédé et compositions pour potentialiser des médicaments à l'aide d'aliments thérapeutiques à base d'acides aminés

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