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Link:  Pharm/Biotech Resources


Title:  Composition and method for treating impaired or deteriorating neurological function

United States Patent:  6,964,969

Issued:  November 15, 2005

Inventors:  McCleary; Edward Larry (1795 Foothills Dr. South, Golden, CO 80401)

Appl. No.:  837562

Filed:  April 19, 2001

Abstract

A nutritional supplement composition for normalizing impaired or deteriorating neurological function in humans is composed of: at least one agent which promotes synthesis of ATP and/or creatine phosphate in the body, at least one antioxidant for scavenging free radicals in at least one pathway in the body; at least one agent for normalizing or maintaining membrane function and structure in the body; at least one agent for normalizing or maintaining normal neurotransmitter function in the body; at least one agent for down-regulating cortisol action; and at least one agent for suppressing activation of apoptotic pathways in the body. The composition may further contain one or more of: at least one agent for suppressing inflammation in the body; at least one agent for normalizing or maintaining vascular wall function and structure in the body; at least one agent for normalizing or maintaining function of nerve growth factors and/or neurotropic factors in the body; at least one agent for suppressing toxic metal ionic effects; at least one agent for normalizing or maintaining methyl metabolism in the body; at least one agent for normalizing or maintaining metabolism of insulin and glucose in the body; and at least one agent for up-regulating activity of heat shock proteins in the body. A method for normalizing impaired neurological function in humans modulating nutrient partitioning in a human involves administering the aforementioned composition to the human, preferably on a daily basis, for a therapeutically effective period of time. Preferably, the method further involves having the human follow a stress reduction program, and/or a cognitive retraining program, and/or a dietary program designed to maximize insulin and glucose metabolism.

SUMMARY OF THE INVENTION

The present invention provides a composition and method for treating impaired neurological function or deteriorating neurological function in the body of a human.

A first aspect of the present invention is directed to a nutritional supplement composition for normalizing impaired or deteriorating neurological function in the body of a human having impaired or deteriorating neurological function, wherein the composition contains effective amounts of:

bullet(A) at least one agent which promotes synthesis of adenosine triphosphate (ATP) and/or creatine phosphate in the body;
bullet(B) at least one antioxidant for scavenging free radicals in at least one pathway in the body;
bullet(C) at least one agent for normalizing or maintaining membrane function and structure in the body;
bullet(D) at least one agent for normalizing or maintaining normal neurotransmitter function in the body;
bullet(E) at least one agent for down-regulating cortisol action; and
bullet(F) at least one agent for suppressing activation of apoptotic pathways in the body; with possible inclusion of one or more of the following:
bullet(G) at least one agent for suppressing inflammation in the body,
bullet(H) at least one agent for normalizing or maintaining vascular wall function and structure in the body;
bullet(I) at least one agent for normalizing or maintaining function of nerve growth factors and/or neurotropic factors in the body;
bullet(J) at least one agent for suppressing toxic metal ionic effects;
bullet(K) at least one agent for normalizing or maintaining methyl metabolism in the body;
bullet(L) at least one agent for normalizing or maintaining metabolism of insulin and glucose in the body; and
bullet(M) at least one agent for up-regulating activity of heat shock proteins in the body.

A second aspect of the present invention is directed to a method for normalizing impaired or deteriorating neurological function in the body of a human having impaired neurological function, wherein the method involves orally administering to the human for a therapeutically effective period of time the composition of this invention. The composition is preferably administered on a daily basis.

The nutritional supplement composition of this invention was developed systematically in a holistic fashion by identifying the multiple, interrelated pathophysiologic pathways and mechanisms which interact to varying degrees and culminate in specific clinical manifestations of neurological system disease, dysfunction or deterioration. Once the important disease-producing pathways were established, each was individually analyzed, and the loci of specific control mechanisms, modulating factors and rate-limiting steps were identified. At each of these loci, therapeutic interventions were developed that were designed to normalize the individual micrometabolic aberrations. Using this model, a therapeutic paradigm was developed to maximize interventional efficacy by capitalizing on the intrinsic synergy of such an approach.

Thus, the present invention not only improves symptomalogy but actually functions at various sites to produce metabolic and physiologic changes which alter, modulate and improve or reverse the basic abnormalities responsible for the development of various neurological diseases.

Furthermore, since the various aberrant pathways are integrated and interrelated to varying degrees and, therefore, functionally augment each other's pathologic effects, the present invention's holistic approach is able to block this negative synergism.

As stated above, the present invention uses a multimodal neurofacilitatory approach. Along with the above-identified approach using nutritional supplements, the present invention also preferably involves a dietary approach designed to optimize glucose and insulin metabolism, a stress reduction program designed to down-regulate the hypothalamic-pituitary-adrenal axis (HPAA) and lower cortisol levels, and/or a cognitive retraining program.

Thus, the present invention produces beneficial effects at many sites in various dysfunctional pathways. The invention prevents, lessens, or reverses the attendant neurological symptomalogy and, at the same time, ameliorates their causative mechanisms.

DETAILED DESCRIPTION OF THE INVENTION

As stated above, the present invention is directed to a composition and a method for normalizing impaired neurological function in the body of a human. The composition is composed of effective amounts of various nutritional supplements which provide a holistic approach to normalizing impaired neurological function. The method of the invention involves the administration of an effective amount of the composition preferably in conjunction with a stress reduction program and/or a cognitive retraining program and/or a dietary plan designed to maximize insulin and glucose metabolism.

As used herein, the term "impaired neurological function" refers to deteriorating or defective neurological function.

With respect to the amounts of the individual components of the composition of this invention, the term "effective amount" means that amount of the component which, when used in combination with the other components in the composition, will provide the composition with the capability of normalizing impaired neurological function in humans.

As stated above, neurons need continuous, substantial production of ATP to fulfill ongoing metabolic requirements. The most rapid way to generate ATP is through phosphorylation of adenosine diphosphate (ADP) by creatine phosphate.

Thus, the composition of this invention includes an effective amount of (A) at least one agent which promotes synthesis of ATP and/or creatine phosphate in the body.

Preferably, component (A) of the composition of this invention is selected from one or more of the following compounds: Co-enzyme Q10, idebenone, taurine, acetyl L-Carnitine (ALC), nicotinamide adenine dinucleotide (NADH), phosphatidyl serine, B-vitamins, vinpocetine, oral creatine (which can be provided as creatine monohydrate), cytidine-5′-diphosphocholine, ribose and alpha lipoic acid (ALA).

As mentioned above, dysfunctional bioenergetics involve abnormalities of substrate supply/metabolism, disturbed passage of high energy electrons along the respiratory chain and impaired calcium homeostasis.

Co-enzyme Q10 facilitates high energy electron transfer along the respiratory chain with resultant augmentation of ATP synthesis. Idebenone, a co-enzyme Q10 analogue, may be used in a similar fashion.

Taurine supplementation is desirable in the present invention because of taurine's ability to beneficially modulate calcium balance in neurons.

ALC, a compound with excellent central nervous system penetration, helps fatty acids across the mitochondrial membrane where the fatty acids may be used as an energy source. ALC enhances brain energy production by improving mitochondrial function and is also a beneficial modulator of mitochondrial DNA synthesis—a process which is closely linked with cellular energy metabolism.

NADH is a nutritional substance which facilitates ATP production in neurons.

Phosphatidyl serine acts as a mitochondrial protectant. It is located within the inner mitochondrial membrane and is intimately involved in mitochondrial function.

B vitamins are cofactors in numerous neuronal bioenergetic pathways, and pharmacologic supplementation ameliorates or normalizes neurologic dysfunction due to poor nutritional intake or excessive neuronal energy demands.

Vinpocetine is a derivative of vincamine which is an extract of the periwinkle. It is a powerful metabolic enhancer by beneficially modulating Krebs Cycle activity and thus stepping up central nervous system (CNS) ATP production.

Oral creatine augments neuronal levels of high energy phosphate compounds in vivo. Oral creatine is preferably provided as creatine monohydrate.

Cytidine-5′-diphosphocholine (CDP-choline) is a donor of choline which is used in the synthesis of both phosphatidyl choline, an important brain phospholipid, and the important neurotransmitter acetyl choline (ACH). Oral administration of CDP-choline also reactivates brain mitochondrial ATPases and the Na/K ATPases.

Ribose is a pentose ring carbohydrate which is well absorbed and may become a rate-limiting substrate in the synthesis of 5-phosphoribose-1-pyrophosphate (PRPP) under conditions of excessive energy demands. Hence, ribose supplementation facilitates cellular energy production and mitochondrial bioenergetics.

Supplementation with the cofactor ALA augments energy production.

In a preferred embodiment, component (A) comprises a combination of oral creatine and ALA. Preferably, in such embodiment, the creatine:ALA ratio ranges from about 1:30 to about 2500:1, more preferably from about 1:10 to about 1000:1.

The composition of this invention also contains (B) at least one antioxidant for scavenging free radicals in at least one pathway in the body. Preferably, component (B) is one or more antioxidants selected from the following: idebenone, co-enzyme Q10, vitamin E, ALA, vitamin C, carnosine, tocotrienols, flavonoids, ALC, vinpocetine, selenium, lycopene, creatine, certain amino acids (e.g., arginine, taurine, and cysteine), NADH, resveratrol, ginkgo biloba, oligomeric proanthocyanidins, and phenolic antioxidants.

Although a single antioxidant can scavenge free radicals in the body, antioxidative therapy is most effective when multiple antioxidants are used as a network, where the antioxidants continuously interact with one another in a beneficial fashion to maximally suppress oxidative events in many interrelated pathways. Thus, in a preferred embodiment, component (B) is composed of two or more, preferably all, of the antioxidants listed above.

In a particularly preferred embodiment, component (B) is composed of a combination of taurine and cysteine. Preferably, the taurine:cysteine ratio in such embodiment ranges from about 1:20 to about 60:1, more preferably from about 1:20 to about 15:1.

The composition of this invention further contains (C) at least one agent for normalizing or maintaining membrane function and structure in the body.

Preferred agents for component (C) include one or more of the following: gamma linolenic acid (GLA); highly polyunsaturated long chain fatty acids such as docosahexanoic acid (DHA), phosphatidyl serine (PS), phosphatidyl choline (PC), phosphatidyl ethanolamine (PE), and phosphatidyl inositol (PI); CDP-choline; methyl donors; S-adenosyl methionine, and antioxidants (e.g., one or more of the antioxidants which can be used as component (B) of the composition of this invention) and sphingosine.

Essential fatty acid deficiency mimics many of the symptoms of ADD/ADHD. This is consistent with an association between alterations in membrane function and the development of specific neurological disease.

CDP-choline plays a major role in the synthesis of phosphatidyl choline, thus protecting the integrity of neuronal cell membranes, membrane function and repair mechanisms.

Oxidative stress reduces the fluidity of the membranous lipid bilayer with subsequent adverse effects upon embedded functional proteins. Antioxidant therapy as well as supplementation with methyl donors or S-adenosyl methionine (SAMe) can mitigate these adverse effects.

Preferably, component (C) comprises a combination of DHA and phosphatidyl serine (PS), preferably at a DHA:PS ratio of from about 1000:1 to about 1:100, more preferably from about 50:1 to about 1:10.

The composition of this invention further comprises (D) at least one agent for normalizing or maintaining normal neurotransmitter function in the body.

Such an agent for component (D) may comprise one or more of the following: (1) an agent for synthesis of various neurotransmitters, non-limiting examples of such a substrate including choline, CDP-choline, phosphatidyl choline, dimethyl minoethanol (DMAE), and various amino acids; (2) an agent for stimulation of production and secretion of neurotransmitters, non-limiting examples of such substrate being phosphatidyl serine (which increases DO, NE and ACH), CDP-choline (which increases DO, ACH and NE), and vinpocetine (which increases NE); (3) an agent for inhibition of enzymes used to degrade various neurotransmitter molecules within the region of the synaptic cleft, a non-limiting example of such substrate being Huperzine A, an acetylcholinesterase inhibitor, (4) a re-uptake inhibitor (e.g., ritalin, which blocks DA re-uptake); (5) an agent that facilitates improved binding at the receptor site (e.g., phosphatidyl serine); (6) a direct agonist (e.g., pergolide, which is a DA agonist); (7) an agent for induction of enzymes used to synthesize neurotransmitters (e.g., soy phytoestrogens, which increase choline-acetyl transferase (CHA); and (8) an agent for augmentation of neurotransmitter receptor sites (e.g., SAMe, which increases ACH receptor sites).

In a preferred embodiment, component (D) comprises a combination of DMAE and huperzine A. Preferably, the DMAE:huperzine A ratio in such embodiment ranges from about 2000:1 to about 1:15, more preferably from about 2000:1 to about 67:1.

Component (E) of the composition of this invention is composed of at least one agent for down-regulating activity of cortisol in the body. Preferably, component (E) comprises one or more agents selected from the group consisting of phosphatidyl serine, DHEA, melatonin, and pyridoxine.

The composition of this invention also contains (F) at least one agent for suppressing activation of apoptotic pathways in the body.

Preferred agents for use as component (F) include one or more of the following: vinpocetine, huperzine A, magnesium, calcium channel blockers, resveratrol, pycnogenol, and lycopene.

Vinpocetine, huperzine A and magnesium each counteract the action of glutamate at NMDA receptors. Glutamate action at NMDA receptors mediates the activation of excitotoxin-induced apoptotic pathways, which in turn can lead to neuronal degeneration.

Activation of NMDA receptors produces elevations in intracellular calcium concentration. Thus, calcium channel blockers and resveratrol (which also decreases calcium influx) can serve a protective function against such elevations in calcium concentration.

Activation of NMDA receptors also increases nitrergic tone within neurons. Pydiogenol counteracts this effect. Any such induced elevation of intraneuronal nitric oxide contributes to the generation of peroxynitrite which is very sensitive to quenching by the action of lycopene.

In a preferred embodiment, component (F) comprises a combination of huperzine A and vinpocetine. In a particularly preferred embodiment, component (F) comprises a combination of huperzine A and vinpocetine in a huperzine A;vinpocetine ratio of from about 1:2 to about 1:200.

Component (G) of the composition of this invention comprises at least one agent for suppressing inflammation in the body.

Preferably, component (G) comprises one or more agents selected from the following: COX-2 inhibitor (e.g., resveratrol), CDP-choline, phosphatidyl serine, DHEA, melatonin, pyridoxine, magnesium, GLA, long chain omega 3 fatty acids, insulin-sensitizing agent (e.g., chromium), antioxidants and vitamin C.

As discussed previously herein, COX-2 mediates inflammation in the body. Thus, COX-2 inhibition forms another therapeutic avenue. Resveratrol is a natural compound with significant COX-2 inhibitory activity.

COX-2 mRNA levels increase in the presence of Interleukin-1 (IL-1). CDP-choline usage lowers IL-1 levels.

Inflammatory processes have been associated with increases in glucocorticoid activity caused by elevated EAA levels within the hypothalamus. Phosphatidyl serine, DHEA, melatonin, vitamin C, and pharmacologic doses of pyridoxine each have anti-cortisolic effects.

Interventions which improve insulin sensitivity are by their very nature anti-inflammatory. Weight loss and specific dietary changes also act in a synergistic fashion to decrease inflammatory mediators.

The mineral magnesium has been shown to have beneficial actions involving the stabilization of neuronal membranes and is able to down-regulate excitatory neurotransmission by direct negative allosteric effects upon the NMDA receptor.

GLA and long chain omega 3 fatty acids play a key role in down-regulating the inflammatory cascade.

Antioxidants are effective at impairing the induction of Nuclear Factor Kappa Beta (NFKB), a potent inflammatory transcription factor.

Component (H) of the composition of this invention comprises at least one agent for normalizing or maintaining vascular wall function and structure in the body.

Preferably, component (H) comprises at least one agent selected from the group consisting of magnesium, L-arginine, L-taurine, antioxidants, insulin-sensitivity enhancers, long chain polyunsaturated fatty acids, vinpocetine, choline, betaine, vitamin B6, vitamin B12, folic acid, and supplemental potassium.

Supplemental magnesium has vasodilatory effects. L-arginine drives the constitutive nitric oxide pathway which further dilates blood vessels and helps to maintain proper endothelial function. Antioxidants play a key role in this regard by preventing inactivation of nitric oxide. Augmentation of insulin sensitivity further enhances these nitric oxide pathways. Supplementation with long chain polyunsaturated fatty acids or vinpocetine enhances red blood cell deformability will subsequent improvements in nutrient delivery through the smallest caliber vascular channels. Elevated serum homocysteine levels are toxic to endothelial cells and impair endothelial cell function.

Augmentation of methylation pathways by the use of nutritional supplements such as creatine, choline, betaine, vitamin B6, vitamin B12, folic acid, dehydroepiandrosterone (DHEA), phosphatidyl serine, S-adenosyl methionine (SAMe), zinc and selenium enhances vascular function and nutrient delivery to the central nervous system. Methyl donors lower homocysteine levels.

Component (I) of the composition of this invention comprises at least one agent for normalizing or maintaining function of nerve growth factors and/or neurotropic factors in the body.

Preferably, component (I) comprises one or more agents selected from the group consisting of estrogenic compounds (e.g., estradiol and soy phytoestrogens), idebenone, and propentofylline.

Estrogenic compounds increase the expression of the anti-apoptotic protein Bcl-XL in hippocampal neurons. This effect represents estrogen transcriptional regulation since a putative estrogen response element has been identified in the bcl-x gene. Enhancement of Bcl-XL is associated with a reduction in measures of beta-Amyloid-induced apoptosis and inhibition of both caspase-mediated proteolysis and neurotoxicity. Both estradiol and soy phytoestrogens have been shown to significantly increase mRNA levels of BDNF which has antiapoptic activity. Hence, soy phytoestrogens are able to act as estrogenic agonists in the brain without possessing the unwanted side effects of enhancing the risk of breast and uterine cancer. Idebenone and propentofylline both enhance the synthesis of nerve growth factors. Agents tending to augment cholinergic tone have also been shown to have a similar neuronal trophic effect. The hormone insulin is also considered functionally to act as a neurotrophic agent. It has anabolic properties which increase neuronal protein synthesis. Neuronal insulin receptors have been described which act to increase glucose metabolism in nerve cells. Resistance to this action of insulin in the brain has been produced by excess glucocorticoid tone as well as by other systemic metabolic abnormalities which decrease insulin sensitivity and subsequently diminish its trophic action.

Component (J) of the composition of this invention comprises at least one agent for suppressing toxic metal ionic effects caused by interaction between toxic metal ions and neuronal constituents in the body. As used herein, the term "toxic metal ionic effects" refers to metal ion activities which impair cellular processes in the body. Examples of toxic metal ions include iron, lead and aluminum.

Preferably, component a) comprises one or more agents selected from the group consisting of desferroximine, alpha-lipoic acid (ALA), zinc, silicon and polyphenolic antioxidants.

Desferroximine and ALA function as chelators for toxic metals in the central nervous system. Zinc, while not acting as a true metal chelator, acts to reverse the adverse effects caused by the interaction of lead with the NMDA receptor. Silicon reduces neuronal aluminum accumulation which may be related to the development of Alzheimer's disease. Polyphenolic antioxidants achieve iron detoxification.

The composition of this invention further comprises (K) at least one agent for normalizing or maintaining methyl metabolism in the body.

Preferably, component (K) comprises one or more agents selected from the group consisting of dehydroepiandrosterone (DHEA), phosphatidyl serine, S-adenosyl methionine (SAMe), choline, folic acid, vitamin B6, vitamin B12, betaine, zinc, selenium, and creatine.

Zinc also plays a key role because of the zinc finger appendages on one of the most important enzymes in DNA regulation, specifically, DNA methyl transferase.

Vitamin B6, DHEA and phosphatidyl serine exhibit cortisol-ameliorating effects. The stress reduction element of the present invention also produces cortisol-ameliorating effects.

SAMe is a high energy methyl donor. SAMe's methyl groups make possible the production of carnitine and creatine (both of which play key roles in cellular bioenergetics); the neuronutrient, acetyl-L-carnitine; the stress hormone and neurotransmitter, adrenaline; the neuronutrient and chief membrane phospholipid, phosphatidyl choline; and the DNA bases, methyladenine and methylcytosine.

SAMe also plays a major role in the synthesis of acetyl choline (ACH), which is one of the most important neurotransmitters, especially involving memory, attention, cognition and executive functioning. The provision of exogenous SAMe has been beneficial as a stand alone agent in ADD/ADHD trials, and use in treatment for depression has been described.

Selenium has been shown to raise SAMe levels when supplemented in its selenomethionine form.

The composition of this invention also contains (L) at least one agent for normalizing or maintaining metabolism of insulin and glucose in the body. Component (L) is designed to improve systemic sensitivity to the insulin. Mechanisms which augment insulin action at the nerve cell membrane facilitate the contribution of glucose to the cellular production of ATP and, in so doing, improve neuronal bioenergetics.

Preferably, component (L) comprises (a) one or more agents which down-regulate glutamatergic tone (e.g., huperzine A or magnesium supplementation), and/or (b) one or more insulin-sensitizing agents (e.g., chromium).

Component (M) of the composition of this invention comprises at least one agent for up-regulating activity of heat shock proteins in the body.

The composition of this invention preferably includes a pharmaceutically acceptable carrier. As used herein, the term "pharmaceutically acceptable carrier" is meant to include one or more pharmaceutically suitable, inactive excipients, carriers, diluents, adjuvants, and lubricants. Non-limiting examples of inactive excipients, carriers, diluents, lubricants, and adjuvants which can be used in the composition of the present invention include: cellulose, substituted cellulose, calcium carbonate, dicalcium phosphate, starches, lactose, modified food starches, dextrose, calcium sulfate, magnesium carbonate, magnesium stearate, stearic acid, glycerin, vegetable oils, polysorbates, lecithin, silicium dioxide, food glaze, talc, croscarmellose sodium, povidone, water and gelatin. Additional inactive excipients, carriers, diluents, lubricants and adjuvants which may be used with the active-ingredient composition of this invention are disclosed in the Handbook of Food Additives (CRC Press), which is incorporated by reference herein in relevant part.

The pharmaceutically acceptable carrier can be present in any conventional amount used in an orally administered composition.

Set forth in the table is a preferred embodiment of the orally administered composition (excluding inactive ingredients) of this invention. The amounts recited in the table represent preferred and more preferred daily dosages of the ingredients listed.

Ingredient Effective Range Preferred Range
 
Thiamine  1 mg-200 mg 10 mg-100 mg
Riboflavin   1 mg-1000 mg 10 mg-500 mg
Niacin   1 mg-3000 mg 25 mg-750 mg
Carnosine   1 mg-1000 mg 20 mg-500 mg
Pyridoxine  1 mg-300 mg 25 mg-200 mg
Folic Acid 50 mcg-10 mg  200 mcg-2 mg  
B 12 25 mcg-2 mg  100 mcg-1 mg  
Biotin 10 mcg-10 mg  50 mcg-2 mg  
Pantothenic Acid  1 mg-500 mg 10 mg-200 mg
Vitamin C  10 mg-2000 mg  50 mg-1000 mg
Vitamin E   1 IU-2000 IU  10 IU-1000 IU
Magnesium (chelated)  10 mg-2000 mg 100 mg-1200 mg
Zinc (chelated)  2 mg-50 mg 5 mg -25 mg
Selenium 10 mcg-600 mg 20 mcg-300 mcg
(as selenomethionine)
Chromium  25 mcg-2000 mcg  50 mcg-1200 mcg
Potassium  5 mg-150 mg 20 mg-100 mg
OPC  2 mg-150 mg 10 mg-75 mg 
Cysteine  100 mg-2000 mg 200 mg-1000 mg
Taurine  100 mg-6000 mg 500 mg-3000 mg
Acetyl L-Carnitine  10 mg-3000 mg  25 mg-2000 mg
Creatine Monohydrate 100 mg-25 g   500 mg-5 g   
DMAE  20 mg-2000 mg 50 mg-200 mg
Choline 20 mg-10 g   50 mg-2 g   
Inositol 20 mg-10 g   50 mg-2 g   
Phosphatidyl Serine   5 mg-1000 mg 50 mg-400 mg
Phosphatidyl Choline   5 mg-2000 mg  50 mg-1000 mg
Phosphatidyl Ethanolamine   5 mg-1000 mg 50 mg-400 mg
Phosphatidyl Inositol   5 mg-2000 mg  50 mg-1000 mg
DHA  10 mg-5000 mg  25 mg-2000 mg
(docosahexanoic acid)
Vinpocetine  1 mg-30 mg 2 mg-20 mg
Huperzine A  10 mcg-500 mcg 50 mcg-300 mcg
Coenzyme Q10   1 mg-1000 mg  5 mg-400 mg
L-Arginine  100 mg-9000 mg 200 mg-8000 mg
Idebenone 100 mg-400 mg 270 mg-360 mg 
GLA  5 mg-500 mg 50 mg-200 mg
Silicon  2 mg-40 mg 5 mg-20 mg
Alpha Lipoic Acid  10 mg-1000 mg 50 mg-600 mg
Resveratrol  10 mg-300 mg 50 mg-200 mg
Soy Isoflavones  10 mg-200 mg 50 mg-100 mg
CDP-Choline  25 mg-1000 mg 100 mg-400 mg 
NADH  1 mg-20 mg 5 mg-10 mg
DHEA  5 mg-200 mg 25 mg-100 mg
Melatonin  .5 mg-15 mg  1 mg-5 mg 
Ribose 500 mg-10 g   1 g-5 g 
Lycopene  1 mg-30 mg 5 mg-15 mg
Betaine  100 mg-3000 mg 500 mg-1500 mg
Gingko Biloba  10 mg-1000 mg 25 mg-600 mg
 

The composition presented in the table above is preferably in the form of an orally administered composition, e.g., powder, chewable wafer, tablet, regular or compressed capsule, etc., wherein the amounts listed are divided into two portions which in combination constitute a single "serving" or "unit dose" of the composition. Each serving is preferably with 8 ounces of water.

The method of this invention involves the steps of administering (preferably daily) for a therapeutically effective period of time to a human having impaired or deteriorating neurological function an effective amount of the composition of this invention. The composition is administered orally or parenterally preferably orally.

As used herein with respect to the amount of the composition used in the method of this invention, the term "effective amount" means an amount sufficient to normalize impaired or deteriorating neurological function in a human. Preferably, the active-ingredient composition (not including inactive ingredients) of this invention is administered in a per serving (e.g., daily) dosage of at least about 1 gram, more preferably from about 1 gram to about 40 grams, most preferably from about 0.25 grams to about 30 grams. When inactive ingredients are present in the composition, the inactive ingredients of the composition can be present in any conventional amount used in orally or parenterally administered compositions.

The term "therapeutically effective period of time" with respect to the administration of the composition in the method of this invention means that period of time sufficient to normalize impaired or deteriorating neurological function in the human. Preferably, the composition of this invention is administered on a daily basis for a period of at least three weeks, more preferably at least six weeks.

As stated above, oral administration is accomplished by ingesting the composition, preferably with water. The orally administered composition of this invention can be in any conventional form including, e.g., capsules (regular or compressed), tablets, chewable wafers, elixirs, powders, granules, suspensions in water or non-aqueous media, sachets, etc.. Powder, tablet, and chewable wafer forms are most preferred.

Alternatively, the composition can be administered parenterally.

As stated above, the method of the present invention may include the human following a stress reduction program which is designed to down-regulate the hypothalamic-pituitary-adrenal axis and lower cortisol levels. The stress reduction program is intended to augment the effects of the nutritional supplement aspect and, if included, the cognitive retraining aspect (discussed below), of the invention. The stress reduction program varies from individual to individual but would involve partaking in activities which reduce stress. Non-limiting examples include, e.g., relaxation, getting a massage, acupuncture, psychotherapy, meditation, taking a sedative, and the like.

The method of the present invention also preferably includes having the human follow a cognitive retraining program. Such a program would act to retrain the brain by inducing changes in neuronal metabolism, neurochemistry/neurotransmission, restructuring of neural circuitry and dendritic/axonal arborization patterns, and increasing synaptosomal surface area and intercellular contacts.

The present invention may further include a nutritional or dietary plan which is designed to improve systemic sensitivity to insulin and to maximize insulin and glucose metabolism. Non-limiting examples include restriction of calories, and/or restriction of refined carbohydrates, and/or restriction of saturated fat, and/or restriction of trans-fat.

Much knowledge has been accumulated regarding etiologic processes as well as possible treatment and/or preventative modalities involving functional brain deterioration. Because of the multiple coexistent pathways of injury which may play a role in any particular scenario, it is no surprise that many prior therapies have been less than effective. However, due to increased understanding of the integrated nature of neuronal pathways of disease, the utility of analyzing all individual pathologic mechanisms at each potentially therapeutic site with the goal of developing a therapy that addresses the entire network of abnormalities involved clearly represents a quantum advance. It is by this analytic process that a truly unique and comprehensive therapeutic paradigm is provided in the present invention.

 

Claim 1 of 5 Claims

1. A composition for treating impaired neurological function or treating deteriorating neurological function in the body of a human, or for promoting neurological health or maintaining neurological health in the body of a human, said composition comprising effective amounts of:

(A) at least one agent which promotes synthesis of ATP and/or creatine phosphate in the body, wherein said (A) agent is selected from the group consisting of creatine monohydrate, alpha lipoic acid, and trimethylglycine;

(B) at least one antioxidant for scavenging free radicals in at least one pathway in the body, wherein said (B) agent is selected from the group consisting of taurine, ginko bioba, lycopene, acetyl L-carnitine, vinpocetine, alpha lipoic acid, coenzyme Q10, and resveratrol;

(C) at least one agent for treating or maintaining membrane function and structure in the body, wherein said (C) agent is selected from the group consisting of inositol and choline;

(D) at least one agent for treating or maintaining normal neurotransmitter function in the body, wherein said (D) agent is selected from the group consisting of DMAE and choline;

(E) at least one agent for down-regulating cortisol action, said (E) agent comprising pyrodoxine; and,

(F) at least one agent for suppressing activation of apoptotic pathways in the body, said (F) agent comprising huperzine;

wherein said (A), (B), (C), (D), (E), and (F) agents are present in said composition in effective amounts for treating impaired neurological function or treating deteriorating neurological function in the body of a human, or for promoting neurological health or maintaining neurological health in the body of a human.

____________________________________________
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