NUTRIGENOMICS METHODS AND COMPOSITIONS

• US 20110189161A1
• Filed: 06/22/2009
• Published: 08/04/2011
• Est. Priority Date: 06/21/2008
• Status: Abandoned Application

• Current Assignee: Downs B. William, Kenneth Blum, Roger L. Waite, William J. Heaney
• Original Assignee: Downs B. William, Kenneth Blum, Roger L. Waite, William J. Heaney
• Inventors: Downs, B. William, Heaney, William J., Blum, Kenneth, Waite, Roger L.
• Application Number:
  US13/000,623
• Publication Number:
  US 20110189161A1
• Time in Patent Office: Days
• US Class Current: 424/94.65
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C12Q 2600/172 Haplotypes

Abstract

The present invention provides a proprietary compositions and systems to modulate genetic and metabolomic contributing factors affecting disease diagnosis, stratification, and prognosis, as well as the metabolism, efficacy and/or toxicity associated with specific vitamins, minerals, herbal supplements, homeopathic ingredients, and other ingredients for the purposes of customizing a subject'"'"'s nutritional supplement formulation to optimize specific health outcomes. Specific to this invention the utilization of certain known polymorphic genes associated with Substance Use Disorder (SUD) are analyzed to target certain genetic anomalies that lead to a high risk and predisposition to SUD. The genotypic patterns are then utilized to provide certain nutritional customized solutions especially related to the attenuation of aberrant abuse of physician prescribed narcotic pain medication across all pain conditions. A priority GENOPROFILE is measured and directs the customization of a subsequent nutraceutical to act as a therapeutic modality. Specifically the treatment includes slow attenuation of the pain medication by incorporating orals (shakes, liquid beverages, pills, tablets, troche, ointments etc.), Intramuscular, Intravenous, intra-rectal and any form necessary to deliver a sufficient amount of an anti-craving and anti-stress nutraceutical. Moreover, the invention includes examples of novel analgesic ointments coupling Synaptamine and such analgesic and other anesthetic compounds including but not limited to Gabapentin, Ketamine, Baclofen, Ketoprofen, Amitriptyline, Lidocaine, Cyclobenzapine, Diclofenac, Menthol, Camphor and Capsaicin. The GENOPROFILE will be used to determine pain sensitivity Intolerance.

Claims

1-65. -65. (canceled)

66. A method of treating a disease state or condition selected from the group consisting of a reward deficiency syndrome (RDS) behavior, a Substance Use Disorder (SUD), acute or chronic pain, inflammation, joint damage, stress, anxiety, sleep loss, insomnia, lethargy, attention deficit hyperactivity disorder, depression, and pre-menstrual dysphorric disorder, comprising administering to a patient determined to have a genotype correlated with the disease state or condition at least the following substances:

a. an opiate destruction-inhibiting amount of at least one substance selected from the group consisting of a D-amino-acid, a peptide, and a structural analogue or derivative of a D-amino-acid or a peptide;

b. a neurotransmitter synthesis-promoting amount of at least one neurotransmitter precursor selected from the group consisting of a dopamine precursor, optionally L-Tyr, L-Phe, or L-Dopa;

a serotonin precursor, optionally L-Trp or 5-hydroxytyrptophane; and

gamma amino butyric acid (GABA) precursor, optionally L-glutamine, l-glutamate or L-glutamic acid; and

c. a tryptophan concentration enhancing amount of at least one chromium salt; and

d. a catecholamine catalytic inhibitor of the enzyme Catecholamine o-methyl-transferase (COMT), optionally selected from the group consisting of any form of Rhodiola and Huperzine,

wherein the substances (a)-(d) are administered as part of one or more compositions.

67. A method according to claim 66 that further comprises administering at least one or more additional substances selected from the group consisting of:

a. a calming herbal component, optionally selected from the group consisting of passion flower or fruit, Black Currant Oil, Black Currant Seed Oil, Ribes nigrum, Borage Oil, Borage Seed Oil, Borago officinalis, Bovine Cartilage, Bromelain, Ananas comosus, Cat'"'"'s Claw, Uncaria tomentosa, cetyl myristoleate, Cetyl-M, cis-9-cetylmyristoleate, Cmo, chondroitin culfate, collagen cydrolysate, collagen, gelatin, gelatine, gelatin hydrolysate, hydrolyzed [denatured] collagen, Devil'"'"'s Claw, Devil'"'"'s Claw Root, Grapple Plant, Wood Spider, Harpagophytum procumbens, Dhea—

Dehydroepiandrosterone, Dimethyl Sulfoxide (DMSO), Evening Primrose Oil, Evening Primrose, Primrose, an Oenothera species (including Oenothera biennis), Feverfew, Tanacetum parthenium, Fish Oil, Flaxseed, Flaxseed Oil, Flax Oil, Linseed Oil, Linum usitatissimum, Ginger, Zingiber officinale, Gingko, Gingko biloba, Ginseng, American ginseng, panax quinquefolius, Asian ginseng, panax ginseng, Siberian ginseng, eleutherococcus senticosus, GLA (Gamma-ü

nolenic Acid), Glucosamine, Glucosamine sulfate, glucosamine hydrochloride, N-acetyl glucosamine, Gotu Kola, Gotu Cola, Brahmi, Brahma-Buti, Indian Pennywort, Centella asiatica, Grapeseed, Grapeseed Oil, Grapeseed Extract, Vitis vinifera, Green Tea, Chinese Tea, Camellia sinensis;

Guggul, Gugulipid, Guggal, Commiphora mukul, Indian Frankincense, Frankincense, Boswellia, Boswellin, Salai Guggal, Boswellia serrata, Kava Kava, Kava, Kava Pepper, Tonga, Kava Root, Piper methysticum, melatonin, MsM (Methylsulfonylmethane), New Zealand Green-Lipped Mussel, Perna Canaliculus, Phellodendron Amurense, Sam-E (S-adenosyl-L-methione), shark cartilage, cartilage, St. John'"'"'s Wort, Hypercium perforatum, Stinging Nettle, Urtica dioica, Thunder God Vine, Tripterygium wilfordii;

Turmeric, Curcuma longa, Curcuma domestica, Type II Undenatured Chicken Collagen, Chicken Collagen, Chicken Type II Collagen, Type II Collagen, Valerian, Valeriana officianalis, White Willow, Willow Bark;

SaNx Alba, White Willow Bark, Wild Yam, Discorea villosa, Ganoderma Lucidum, Mangosteen Extract, Quercetin, and a combination of any two or more of the foregoing; and

/or

b. a vitamin component, optionally selected from the group consisting of Folic Acid, Vitamin D, Vitamin C, and Vitamin B₆, and a combination of any two or more of the foregoing vitamin components; and

/or

c. mineral component, optionally selected from the group consisting of manganese, potassium, magnesium, calcium, coral calcium, Sierasil®

, Algae Cal®

, and any active salt thereof; and

/or

d. a homeopathic component, optionally selected from the group consisting of Aceonite 12×

;

Belladonna 12×

;

Bryonia 12×

;

Chamonlia 6×

;

Ferrum Phos 12×

;

Gelsemium 12×

; and

Berberis 6×

.

68. A method according to claim 66 that includes at least one of the following:

a. the D-amino-acid is selected from the group consisting of D-phenylalanine;

D-Leucine; and

hydrocinnamic acid; and

/or

b. the neurotransmitter synthesis precursor is selected from the group consisting of a dopamine precursor, optionally L-Tyr, L-Phe, or L-dopa;

a serotonin precursor, optionally L-Trp or 5-hydroxytryptophan;

a gamma amino butyric acid (GABA) precursor, optionally L-glutamine, L-glutamic acid, or L-glutamate;

an acetylcholine (ACH) or acetylcarnitine precursor, optionally L-choline or L-acetylcholine;

L-carnitine; and

aceyticarnitine; and

/or

c. the chromium salt is selected from the group consisting of picolinate, polynicotinate, chloride, and any active salt thereof.

69. A method according to claim 66 comprising daily administration of:

a. approximately 32-10,000 mg of DL-phenylalanine, 10-10,000 mg of L-tyrosine, 5-5,000 mg of L-tryptophan, 3-30,000 mg of L-glutamine, 2-30,000 mg of chromium salt, 1-300 mg of pyridoxal-5′

-phosphate, and 1-10,000 mg Rhodiola rosea;

or

b. 2-2000 mg Passion flower;

5-1500 mg Kava Kava;

5-10,000 mg Rhodiola rosea;

5-10,000 mg Rhodendron;

5-10,000 mg DL-phenylalanine;

2-5000 mg L-tyrosine;

10-5,000 mg L-glutamine;

5-2000 mg 5-Hyroxytryptophane;

20-30,000 mg Chromium Picolinate or other active salt thereof;

1-1000 mg Pyridoxal phosphate;

1-1000 mg Vitamin B complex;

5-2000 mg Calcium citrate;

5-2000 mg Magnesium ascorbate;

10-20,000 mg Hydroxycitric acid (a potassium salt); and

2-2000 mg Magnolia.

70. A method according to claim 69(a) further comprising daily administration of 5-10,000 mg Algae Cal®

and/or 5-10,000 mg Coral Calcium.

71. A method according to claim 66 wherein determination of whether a patient has a genotype correlated with the disease state or condition is made by performing an allelic analysis of nucleic acids, optionally DNA, obtained from a sample taken from a subject known or suspected to have the disease state or condition, wherein (i) the sample is optionally a buccal sample or a blood sample and/or (ii) the allelic analysis analyzes at least two genes to identity mutations in the genes, wherein identifying mutations optionally comprises measuring multiple genetic mutations through single nucleotide polymorphisms or gene expression.

72. A method according to claim 71 wherein the allelic analysis comprises identifying at least one mutation selected from the group consisting of:

a polymorphism in a gene encoding a Beta-adrenergic receptor;

a polymorphism in a gene encoding an angiotensin converting enzyme (ACE);

a polymorphism in a gene encoding an angiotensin 11 TI receptor;

a polymorphism in a gene encoding cholesteryl ester transfer protein;

a polymorphism in a gene encoding a potassium channel;

a polymorphism in a gene encoding a cytochrome P-450 enzyme, optionally CYP2D6;

a polymorphism in a gene encoding a protein product of the HER2/neu oncogene;

a polymorphism of the C825T gene;

a polymorphism in the APOE gene locus);

a polymorphism in the CT or TT allele of the dopamine D2 receptor gene;

a SNP (polymorphism) designated AA, at nucleotide position−

6 of the ANG gene;

a polymorphism in a gene encoding Apo-A1;

a polymorphism in a gene encoding Methylene Tetrahydrofolate Reductase (MTHFR), optionally a C677T polymorphism;

a polymorphism in tumor necrosis factor (TNF) gene;

a polymorphism in the carbohydrate responsive element-binding protein (ChREBP) gene;

a polymorphism of the Leptin receptor gene;

a polymorphism of the dopamine D2 receptors gene (DRD2);

a polymorphism of any of the dopamine D1, D3, D4, and D5 genes;

a dopamine D2 receptor polymorphism selected from the group consisting of Ser311cys and TaqIA;

a polymorphism in a c-fos gene;

a polymorphism in the c-jun gene;

a polymorphism in the c-myc, gene;

a polymorphism in a gene encoding Sterol Regulatory Element Protein-1 (SREBP-Ic);

a polymorphism in a gene encoding mitochondrial glycerol-3-phosphate acetyltransferase gene (MGPAT);

a polymorphism in a gene encoding the peroxisome proliferator-activated receptor PPAR-gamma-2) gene;

the Prol2Ala polymorphism of the PPARgamma gene;

a polymorphism in a gene encoding Tryptophan 2,3-Dioxygenase (TDO2);

a polymorphism in a gene encoding TCP-I;

a polymorphism in a gene encoding Mc4R;

a polymorphism in a gene encoding CART;

a polymorphism in a gene encoding interleukin-1 beta;

a polymorphism in a gene encoding tumor necrosis factor-alpha;

a polymorphism in a gene encoding an intracellular adhesion molecule;

a polymorphism in a gene encoding interleukin-8, a polymorphism in a gene encoding and interleukin-10;

a polymorphism in a gene encoding interferon-alpha;

a polymorphism in a gene encoding Ras-Protein and (HLA-DRBI 0404 and OlOlor PTPN22 R620W);

the Dopamine Receptor D3 Ser9Gly (−

205-G/A, -7685-G/C) polymorphism;

a polymorphism in a gene encoding Glutamine;

fructose-6-phosphate amidotransferase (GFPTI or GFPT

     2), optionally polymorphisms in exon 14, optionally 1471V, or 3′

UTR;

or a polymorphism in a gene encoding glucosamine 6-P acyltransferase;

a polymorphism in Aggrecan proteoglycan allele 27;

a polymorphism in a gene encoding 11-beta hydroxysteroid dehydrogenase typel;

a polymorphism in a gene encoding FK506 binding protein 5;

a polymorphism in a gene encoding serum/glucosteroid kinase;

a polymorphism in a gene encoding tryptophan 2,3 dioxygenase;

a polymorphism in a gene encoding Myelin;

a polymorphism in a gene encoding a Myelin associated glycoprotein, optionally myelin oligodendrocyte glycoprotein (MOG), optionally a polymorphism in a tetranucleotide TAAA repeat (MOG4), C10991T SNP;

a polymorphism in a gene encoding Edg2;

a polymorphism in a gene encoding Fgfr2;

a polymorphism in a gene encoding Decorin;

a polymorphism in a gene encoding Brevican;

a polymorphism in a gene encoding Neurotensin (NT) receptors-1;

a polymorphism in a gene encoding Neurotensin (NT) receptor-2;

a polymorphism in a gene encoding Neurotensin (NT) receptor-3;

a polymorphism in a gene encoding Proenkephalin;

a polymorphism in a gene encoding prodynorphin, optionally 946C>

G;

a polymorphism in a gene encoding Bdnf (Neurotrophic Factor, optionally BDNF Va166Met and −

281 C>

A, T allele of the C270T);

a polymorphism in a gene encoding Sgk (Serum- and glucose-regulated kinase (SGK

     1), optionally SNP Intron 6, Exon 8 (CC, CT, TT);

a polymorphism in a gene encoding Gabl;

Id2;

a polymorphism in a gene encoding COMT;

a polymorphism in a gene encoding ANKKI;

a polymorphism in a gene encoding DATI;

a polymorphism in a gene encoding DBH;

a polymorphism in a gene encoding HTT;

a polymorphism in a gene encoding HTRIA;

a polymorphism in a gene encoding HTRID;

a polymorphism in a gene encoding HTR2A;

a polymorphism in a gene encoding HTR2c, optionally 5-HT-2A, 5-HT 2B, 5-HT-4, and 5-HT-7);

a polymorphism in a gene encoding ADRA2A;

a polymorphism in a gene encoding ADRA2;

a polymorphism in a gene encoding NET;

a polymorphism in a gene encoding MAOA;

a polymorphism in a gene encoding GABRA3;

a polymorphism in a gene encoding GABRB3;

a polymorphism in a gene encoding CNRI;

a polymorphism in a gene encoding CNRA4;

a polymorphism in a gene encoding NMDARI;

a polymorphism in a gene encoding POMC;

a polymorphism in a gene encoding MGPAT;

a polymorphism in a gene encoding NYP;

a polymorphism in a gene encoding AgRP;

a polymorphism in a gene encoding OBR;

a polymorphism in a gene encoding Mc3R;

UCP-1;

a polymorphism in a gene encoding GLUT4;

a polymorphism in a gene encoding PDGS;

a polymorphism in a gene encoding ALdB;

a polymorphism in a gene encoding LNC2;

a polymorphism in a gene encoding E23K Kir6.2;

a polymorphism in a gene encoding steroid sulfatase (STS);

a polymorphism G82G in PTPNI;

the IVS6+G82A polymorphism;

a polymorphism in a gene encoding Sulfonylurea receptor 1;

a polymorphism in a gene encoding beta(3)-AR Trp64Arg;

a polymorphism in a gene encoding PC1;

a polymorphism in a GHRELIN gene;

a polymorphism in a gene encoding FKBP5;

a polymorphism in a gene encoding a VITAMIN D RECEPTOR, optionally BSMI AND FOKI;

a polymorphism in a gene encoding lymphoid tyrosine phosphatase (LYP), optionally a polymorphism in a gene encoding protein tyrosine phosphatase-22 (PTPN22) gene, and a polymorphism in a gene encoding any sodium ATPAse.

73. A method according to claim 71 wherein the allelic analysis comprises identifying at least one mutation that is a polymorphism selected from the group consisting of a polymorphism (Rs value of SNP) of a gene encoding DRD2 (RsI800497, Rs6278, Rs6276, RsIO79594, Rs6275, RsI801028, RsI076560, Rs2283265, RsIO79727, RsIO76562, RsII25394, Rs4648318, Rs4274224, Rs7131056, Rs4648317, RsI799732, RsI799978;

5HT2A(Rs6314, Rs3742278, Rs6561333, RsI923886, Rs643627, Rs2770292, RsI928040, Rs2770304, Rs594242, Rs6313;

ANKKI (RS2734849, RS1800497, RsII604671, Rs4938016);

OPRKI (Rs35160174, Rs35373196, Rs34709943 RS6473797) OPRMI (Rs510769, Rs553202, Rs514980, Rs561720, Rs534673, Rs524731, Rs3823010, Rs3778148, Rs7773995, R5495491, RsI2333298, RsI461773, RsI381376, Rs3778151, Rs506247, Rs563649, Rs9479757, Rs2075572, RsI0485057, Rs540825, Rs562859, Rs548646, Rs648007, Rs9322447, Rs681243, Rs609148, Rs3798687, Rs648893);

COMT (Rs737864, Rs933271, Rs5993882, Rs740603, Rs4646312, RsI65722, Rs6269, RsI7699);

SLC6A3 (RsI2516948, RsI042098, Rs40184, RsII564773, RsIII33767, Rs6876225, Rs3776512, Rs2270912, Rs6347, Rs27048, Rs37022, Rs2042449, Rs464069, Rs463379, Rs403636, Rs2617605, RsI3189021, Rs6350, Rs2975223, Rs2963238, RsI1564752 Rs2975226);

HTR3B(Rs3758987, Rs2276307, Rs3782025, RsI672717);

NOS3 (Rs891512, RsI808593, Rs2070744, Rs3918226, Rs7830);

PPARG (RsI801282, Rs2938392, RsI175542, RsI7036314, RsI805192, Rs4684847, Rs2938392, Rs709157, Rs709158, RsI175542);

ChREBP(Rs3812316);

FTO (Rs8050136, RsI421084, Rs9939609, RsI861868, Rs9937053, Rs9939973, Rs9940128, RsI558902, RsI0852521, RsI477196, RsI121980, Rs7193144, RsI6945088, Rs8043757, Rs3751812, Rs9923233, Rs9926289, RsI2597786, Rs7185735, Rs9931164, Rs9941349, Rs7199182, Rs9931494, RsI7817964, Rs7190492, Rs9930506, Rs9932754, Rs9922609, Rs7204609, Rs8044769, RsI2149832, Rs6499646, RsI421090, Rs2302673);

TNFalpha (RsI799964, RsI800629, Rs361525, RsI800610, Rs3093662);

MANEA (RsI133503);

LeptinOb (Rs4728096, RsI2536535, Rs2167270, Rs2278815, RsI0244329, RsII763517, RsII760956, RsIO954173);

PEMT (Rs4244593, Rs936108);

MAO-A (Rs3788862, RsI465108, Rs909525, Rs2283724, RsI2843268, RsI800659, Rs6323, RsI799835, Rs3027400, Rs979606, Rs979605 RsI137070);

CRH (Rs7209436, Rs4792887, RsI10402, Rs242924, Rs242941, Rs242940, Rs242939, Rs242938, RsI73365, RsI876831, RsI876828, Rs937, Rs878886 Rs242948);

ADIPOQ (RsI7300539, Rs2241766);

STS (RsI2861247);

VDR(RsI7467825, Rs731236, RsI544410, Rs2229828, Rs2228570, Rs2238136);

DBI (Rs3091405, Rs3769664, Rs3769662, Rs956309, Rs8192506);

GABRA6 (Rs3811995, Rs3219151, Rs6883829, Rs3811991);

GABRB3 (Rs2912582, Rs2081648, RsI426217, Rs754185, Rs890317, Rs981778, Rs2059574);

MTHFR(Rs4846048, RsI801131, RsI801133, Rs2066470);

MLXIPL[carbohydrate binding element] (Rs3812316, RsI7145738);

VEGF (Rs2010963, Rs833068, Rs3025000, Rs3025010, Rs3025039, Rs3025053);

DRD4 (Rs936460, Rs41298422, Rs3758653, Rs936461, RsI2720373, Rs747302, RsI800955, Rs916455, Rs916457, Rs7

     124601);

CLOCK (RsI801260, Rs934945, RsI3033501);

Melatonin (any polymorphism);

Orexin (all polymorphisms), PENK (RS16920581, RS1437277, RS1975285, RS260998, RS2609997), and CBI (RS1049353).

74. A method according to claim 66 wherein:

a. the disease state or condition is joint damage caused by rheumatoid arthritis and the determined genotype comprises allelic analysis of polymorphisms in the tumor necrosis factor (TNF) gene informs a differential response to fish oil supplementation for the treatment of rheumatoid arthritis;

or

b. the disease state or condition is inflammation and the determined genotype comprises allelic analysis of polymorphisms in the tumor necrosis factor (TNF) gene informs a differential response to vitamin E for promoting anti-oxidant activity and reducing inflammatory processes;

or

c. the disease state or condition is pain intolerance and the determined genotype comprises allelic analysis of polymorphisms in the dopamine D2 receptor gene informs a differential response to a chromium salt;

or

d. the disease state or condition is pain and the determined genotype comprises allelic analysis of polymorphisms in a gene selected from the group consisting of the dopamine D2, D1, D3, D4, and D5 receptor genes is used to adjust a dosage of one or more of (i) the substance selected from the group consisting of a D-amino-acid, a peptide, and a structural analogue or derivative of a D-amino-acid or a peptide, (ii) the neurotransmitter precursor, (iii) the chromium salt, and/or (iv) the catecholamine catalytic inhibitor, for pain control;

or

e. the determined genotype comprises allelic analysis of polymorphisms in the human TDO2 gene and informs adjusting dosage of L-tryptophan, 5-hydroxytryptophan, and/or a chromium salt;

or

f. the determined genotype comprises allelic analysis of polymorphisms in a gene selected from the group consisting of the interleukin-1 alpha gene, interleukin-1 beta gene, the TNF-alpha gene, the intracellular adhesion molecule gene, the interleukin-8 gene, and the interleukin-10 gene informs adjusting dosage of Echinacea;

or

g. the determined genotype comprises allelic analysis of polymorphisms in the Methylene Tetrahydrofolate Reductase (MTHFR) gene, optionally the C677T polymorphism, informs adjusting dosage of a vitamin, optionally, folic acid, also administered to the patient;

or

h. the determined genotype comprises allelic analysis of polymorphisms in the hippocalcin like 1 (Hpcall) gene informs adjusting dosage of a mineral, optionally, calcium, also administered to the patient;

or

i. the determined genotype comprises allelic analysis of polymorphisms in a gene selected from the group consisting of the proenkephalin gene, prodynorphin gene, neurotensin (1,2,3) gene, the Bdnf gene, the TD02 gene, the Sgk gene, the Fkbp5&

4 gene, the Edg2 gene, the Id2 gene, and the Gabl Fgfr2 gene to informs adjusting dosage of an herbal component, optionally, Passion flower, also administered to the patient as part of the method;

or

j. the determined genotype comprises allelic analysis of polymorphisms in a gene selected from the group consisting of the proenkephalin gene, prodynorphin gene, neurotensin (1,2,3) gene, the Bdnf gene, the TD02 gene, the Sgk gene, the Fkbp5&

4 gene, the Edg2 gene, the Id2 gene, and the Gabl Fgfr2 gene to inform adjusting dosage of Rhodiola, optionally, Rhodiola rosea;

k. the determined genotype comprises allelic analysis of polymorphisms in a gene selected from the group consisting of the COMT gene, the proenkephalin gene, the prodynorphin gene, the neurotensin (1,2,3) gene, the Bdnf gene, the TD02 gene, the Sgk gene, the Fkbp5&

4 gene, the Edg2 gene, and Id2 gene to informs adjusting dosage of Rhodendron that is also administered to the patient as part of the method;

l. the determined genotype comprises allelic analysis of polymorphisms in a gene selected from the group consisting of the COMT gene, the DRD1-5 gene, the ANKKI gene, the DATI gene, the DBH gene, the TD02 gene, the HTT gene, the HTRIA gene, the HTRID gene, the HTR2A gene, the HTR2c gene, the ADRA2A gene, the ADRA2 gene, the NET gene, the MAOA gene, the GABRA3 gene, the GABRB3 gene, the CNR1 gene, the CNRA4 gene, the NMDAR1 gene, the POMC gene informs adjusting dosage of dl-phenylalanine;

or

m. the determined genotype comprises allelic analysis of polymorphisms in a gene selected from the group consisting of the COMT gene, the NET gene, the MAOA gene, any of the DRD1-5 genes, ANKKI gene, the DATI gene, the DBH gene, the POMC gene, the proenkephalin gene, the prodynorphin gene, the neurotensin (1 gene, the 2 gene, the3) Bdnf gene, the TD02 gene, the Sgk gene, the Fkbp5&

4 gene, the Edg2 gene, the Id2 gene, and the GabI Fgfr2 gene informs adjusting dosage of L-Tyrosine;

or

n. the determined genotype comprises allelic analysis of polymorphisms in a gene selected from the group consisting of the COMT gene, the NET gene, the MAOA gene, the POMC gene, the proenkephalin gene, the prodynorphin gene, any neurotensin (1, 2, or

     3) gene, the GABRA3 gene, and the NMDAR1 gene the informs adjusting dosage of the neurotransmitter precursor, optionally L-glutamine;

or

o. the determined genotype comprises allelic analysis of polymorphisms in a gene selected from the group consisting of the COMT gene, the NET gene, the MAOA gene, the POMC gene, the proenkephalin gene, the proenkephalin gene, the prodynorphin gene, any neurotensin (1, 2, or

     3) gene, the TD02 gene, the HTT gene, the HTRIA gene, the HTRID gene, the HTR2A gene, and the HTR2c gene informs adjusting dosage of the neurotransmitter precursor, optionally 5-Hyroxytryptophane;

or

p. the determined genotype comprises allelic analysis of polymorphisms in a gene selected from the group consisting of the COMT gene, the NET gene, the MAOA gene, the POMC gene, the proenkephalin gene, the prodynorphin gene, any neurotensin (1, 2, or

     3) gene, the TD02 gene, the HTT gene, the HTRIA gene, the HTRID gene, the HTR2A gene, the HTR2c gene, the DRD1-5 gene, the ANKKI HTR2A gene, the HTR2c gene, the DRD1-5 gene, the ANKKI gene, the DATI gene, and the DBH gene informs adjusting dosage of a chromium salt;

or

q. the determined genotype comprises allelic analysis of polymorphisms in a gene selected from the group consisting of the HTT gene, the HTRIA gene, the HTRID gene, the HTR2A gene, the HTR2c, the 5-HT-2A gene, the 5-HT 2B gene, the 5-HT-4 gene, the 5-HT-7 gene, the COMT gene, any of the DRD1-5 genes, the ANKKI gene, the DATI gene, the DBH gene, the TD02 gene, the ADRA2A gene, the ADRA2 NET gene, the MAOA gene, the GABRA3 gene, the GABRB3 gene, the CNR1 gene, the CNRA4 gene, the NMDAR1 gene, the POMC gene, the proenkephalin gene, the prodynorphin gene, any neurotensin (1, 2, or

     3) gene, the Bdnf gene, the TD02 gene, the Sgk gene, the Fkbp5&

4 gene, the Edg2 gene, the Id2 gene, the Gabl gene, and the Fgfr2 gene informs adjusting dosage of (−

)-Hydroxycitric acid (HCA) also administered to the patient as part of the method;

or

r. the determined genotype comprises allelic analysis of polymorphisms in a gene selected from the group consisting of the Hpcall gene, the COMT gene, the NET gene, and the MAOA gene informs adjusting dosage of Pyridoxal phosphate also administered to the patient as part of the method;

s. the determined genotype comprises allelic analysis of polymorphisms in a gene selected from the group consisting of the HpcaII gene and any ATPase gene informs adjusting dosage of magnesium also administered to the patient as part of the method;

or

t. the determined genotype comprises allelic analysis of polymorphisms in a gene selected from the group consisting of the leptin receptor gene, any of the dopamine DI-5 genes, the HpcaII gene, the HTT gene, the HTRIA gene, the HTRID gene, the HTR2A gene, the HTR2c gene, they-HT-2A gene, the 5-HT 2B gene, the 5-HT-4 gene, the 5-HT-7 gene, the ANKKI gene, the DATI gene, the DBH gene, and the TD02 gene informs adjusting dosage of potassium also administered to the patient as part of the method.

75. A method according to claim 66 that further comprises administering at least one or more additional substances selected from the group consisting of (−

)-Hydroxycitric acid (HCA), Passion flower (Passiflora incarnata) L Extract, Potassium, Thiamin, Vitamin B₅, and Calcium, wherein the additional substance(s) is(are) optionally each administered in a daily dosage ranging from approximately 1 meg to 30,000 mg.

76. A method according to claim 66 that further comprises administering a pain-alleviating ointment formulation, wherein the ointment formulation optionally comprises a base ointment cream comprising a solubilizer, wherein the solubilizer optionally is selected from the group consisting of a soya-lecithin aggregate;

a micronized, cyclic monoterpene;

a cyclohexanone derivative;

isosorbide dinitrate; and

Lipoderm.

77. A pain-alleviating ointment formulation for use in practicing a method according to claim 76, wherein the ointment formulation is selected from the group consisting of:

a. an ointment formulation comprising D-phenylalanine, wherein the ointment formulation optionally is selected from the group consisting of D-phenylalanine, LID, GBP, KET, KEPF (optionally in the ratio of about 10/5/10/10/10%);

D-Phenylanine, GBP, KET, BAC (optionally in the ratio of about 10/10/10/4%);

D-Phenylalanine GBP, KET, LID (optionally in the ratio of about 10/6/10/10%);

D-Phenylanine, GBP, KET, AM, BAC (optionally in the ratio of about 10/6/6/4/4%);

D-Phenylalanine, KEPF (optionally in the ratio of about 10/10%);

D-Phenylalanine, KEPF (optionally in the ratio of about 10/20%);

D-Phenylalanine, KEPF, LID (optionally in the ratio of about 10/10/5%);

D-Phenylalanine, KEPF, CLB(optionally in the ratio of about 10/20/2%);

D-Phenylalanine, KEPF, LID, CLB (optionally in the ratio of about 10/20/5/2%);

D-Phenylalanine, IBUF, KEPF, CLB (optionally in the ratio of about 10/10/10/1%);

D-Phenylalanine, LID (optionally in the ratio of about 10/10%);

D-Phenylalanine, DICLO (optionally in the ratio of about 10/10%);

D-phenylalanine, CAP, MT, CAMP (optionally in the ratio of about 10/0.0375%);

D-phenylalanine, CAP, MT, CAMP (optionally in the ratio of about 10/05%); and

D-phenylalanine KEPF, KET, CAP (optionally in the ratio of about 10/10/6/0.075%);

b. an ointment formulation comprising L-phenylalanine, wherein the ointment formulation optionally is selected from the group consisting of L-phenylalanine, LID, GBP, KET, KEPF (optionally in the ratio of about 10/5/10/10/10%);

L-Phenylanine, GBP, KET, BAC (optionally in the ratio of about 10/10/10/4%);

L-Phenylalanine GBP, KET, LID (optionally in the ratio of about 10/6/10/10%);

L-Phenylanine, GBP, KET, AM, BAC (optionally in the ratio of about 10/6/6/4/4%);

L-Phenylalanine, KEPF (optionally in the ratio of about 10/10%);

L-Phenylalanine, KEPF (optionally in the ratio of about 10/20%);

L-Phenylalanine, KEPF, LID (optionally in the ratio of about 10/10/5%);

L-Phenylalanine, KEPF, CLB (optionally in the ratio of about 10/20/2%);

L-Phenylalanine, KEPF, LID, CLB (optionally in the ratio of about 10/20/5/2%);

L-Phenylalanine, IBUF, KEPF, CLB (optionally in the ratio of about 10/10/10/1%);

L-Phenylalanine, LID (optionally in the ratio of about 10/10%);

L-Phenylalanine, DICLO (optionally in the ratio of about 10/10%);

L-phenylalanine, CAP, MT, CAMP (optionally in the ratio of about 10/0.0375%);

L-phenylalanine, CAP, MT, CAMP (optionally in the ratio of about 10/05%);

L-phenylalanine, KEPF, KET, CAP (optionally in the ratio of about 10/10/6/0.075%);

c. an ointment formulation comprising L-Glutamine, wherein the ointment formulation optionally is selected from the group consisting of L-Glutamine, LID, GBP, KET, KEPF (optionally in the ratio of about 10/5/10/10/10%);

L-Glutamine, GBP, KET, BAC (optionally in the ratio of about 10/10/10/4%);

L-Glutamine, GBP, KET, LID (optionally in the ratio of about 10/6/10/10%);

L-Glutamine, GBP, KET, AM, BAC (optionally in the ratio of about 10/6/6/4/4%);

L-Glutamine, KEPF (optionally in the ratio of about 10/10%);

L-Glutamine, KEPF (optionally in the ratio of about 10/20%);

L-Glutamine, KEPF, LID (optionally in the ratio of about 10/10/5%);

L-Glutamine, KEPF, CLB (optionally in the ratio of about 10/20/2%);

L-Glutamine, KEPF, LID, CLB (optionally in the ratio of about 10/20/5/2%);

L-Glutamine IBUF, KEPF, CLB (optionally in the ratio of about 10/10/10/1%);

L-Glutamine, LID (optionally in the ratio of about 10/10%);

L-Glutamine, DICLO (optionally in the ratio of about 10/10%);

L-Glutamine, CAP, MT, CAMP (optionally in the ratio of about 10/0.0375%);

L-Glutamine, CAP, MT, CAMP (optionally in the ratio of about 10/05%);

L-Glutamine KEPF, KET, CAP (optionally in the ratio of about 10/10/6/0.075%);

d. an ointment formulation comprising 5-HTP, wherein the ointment formulation optionally is selected from the group consisting of 5-HTP, LID, GBP, KET, KEPF (optionally in the ratio of about 10/5/10/10/10%);

5-HTP, GBP, KET, BAC (optionally in the ratio of about 10/10/10/4%);

5-HTP GBP, KET, LID (optionally in the ratio of about 10/6/10/10%);

5-HTP, GBP, KET, AM, BAC (optionally in the ratio of about 10/6/6/4/4%);

5-HTP, KEPF (optionally in the ratio of about 10/10%);

5-HTP, KEPF (optionally in the ratio of about 10/20%);

5-HTP, KEPF, LID (optionally in the ratio of about 10/10/5%);

5-HTP, KEPF, CLB (optionally in the ratio of about 10/20/2%);

5-HTP, KEPF, LID, CLB(optionally in the ratio of about 10/20/5/2%);

5-HTP, IBUF, KEPF, CLB (optionally in the ratio of about 10/10/10/1%);

5-HTP, LID (optionally in the ratio of about 10/10%);

5-HTP, DICLO (optionally in the ratio of about 10/10%);

5-HTP, CAP, MT, CAMP (optionally in the ratio of about 10/0.0375%);

5-HTP, CAP, MT, CAMP (optionally in the ratio of about 10/05%);

5-HTP, KEPF, KET, CAP (optionally in the ratio of about 10/10/6/0.075%);

e. an ointment formulation comprising Rhodiola rosea, wherein the ointment formulation optionally is selected from the group consisting of Rhodiola rosea, LID, GBP, KET, KEPF (optionally in the ratio of about 10/5/10/10/10%);

Rhodiola rosea, GBP, KET, BAC (optionally in the ratio of about 10/10/10/4%);

Rhodiola rosea GBP, KET, LID (optionally in the ratio of about 10/6/10/10%);

Rhodiola rosea, GBP, KET, AM, BAC (optionally in the ratio of about 10/6/6/4/4%);

Rhodiola rosea, KEPF (optionally in the ratio of about 10/10%);

Rhodiola rosea, KEPF (optionally in the ratio of about 10/20%);

Rhodiola rosea, KEPF, LID (optionally in the ratio of about 10/10/5%);

Rhodiola rosea, KEPF, CLB (optionally in the ratio of about 10/20/2%);

Rhodiola rosea, KEPF, LID, CLB (optionally in the ratio of about 10/20/5/2%);

Rhodiola rosea IBUF, KEPF, CLB (optionally in the ratio of about 10/10/10/1%);

Rhodiola rosea, LID (optionally in the ratio of about 10/10%);

Rhodiola rosea, DICLO (optionally in the ratio of about 10/10%);

Rhodiola rosea, CAP, MT, CAMP (optionally in the ratio of about 10/0.0375%);

Rhodiola rosea, CAP, MT, CAMP (optionally in the ratio of about 10/05%);

Rhodiola rosea, KEPF, KET, CAP (optionally in the ratio of about 10/10/6/0.075%);

f. an ointment formulation comprising chromium salt, wherein the ointment formulation optionally is selected from the group consisting of chromium salt, LID, GBP, KET, KEPF (optionally in the ratio of about 0.01/5/10/10/10%);

chromium salt, GBP, KET, BAC (optionally in the ratio of about 0.01/10/10/4%);

chromium salt GBP, KET, LID (optionally in the ratio of about 0.01/6/10/10%);

chromium salt, GBP, KET, AM, BAC (optionally in the ratio of about 0.01/6/6/4/4%);

chromium salt, KEPF (optionally in the ratio of about 0.01/10%);

chromium salt, KEPF (optionally in the ratio of about 0.01/20%);

chromium salt, KEPF, LID (optionally in the ratio of about 0.01/10/5%);

chromium salt, KEPF, CLB (optionally in the ratio of about 0.01/20/2%);

chromium salt, KEPF, LID, CLB (optionally in the ratio of about 0.01/20/5/2%);

chromium salt, IBUF, KEPF, CLB (optionally in the ratio of about 0.01/10/10/1%);

chromium salt, LID (optionally in the ratio of about 0.01/10%);

chromium salt, DICLO(optionally in the ratio of about 0.01/10%);

chromium salt, CAP, MT, CAMP (optionally in the ratio of about 0.01/0.0375%);

chromium salt, CAP, MT, CAMP (optionally in the ratio of about 0.01/05%);

chromium salt, KEPF, KET, CAP (optionally in the ratio of about 0.01/10/6/0.075%);

g. an ointment formulation comprising Pyridoxal-phosphate, wherein the ointment formulation optionally is selected from the group consisting of Pyridoxal-phosphate, LID, GBP, KET, KEPF (optionally in the ratio of about 0.05/5/10/10/10%);

Pyridoxal-phosphate, GSP, KE T, BAC (optionally in the ratio of about 0.05/10/10/4%);

Pyridoxal-phosphate, GSP, KET, LID (optionally in the ratio of about 0.01/6/10/10%);

Pyridoxal-phosphate, GBP, KET, AM, BAC (optionally in the ratio of about 0.05/6/6/4/4%);

Pyridoxal-phosphate, KEPF (optionally in the ratio of about 0.05/10%);

Pyridoxal-phosphate, KEPF (optionally in the ratio of about 0.05/20%);

Pyridoxal-phosphate, KEPF, LID (optionally in the ratio of about 0.05/10/5%);

Pyridoxal-phosphate, KEPF, CLB (optionally in the ratio of about 0.05/20/2%);

Pyridoxal-phosphate, KEPF, LID, CLB(optionally in the ratio of about 0.01/20/5/2%);

Pyridoxal-phosphate IBUF, KEPF, CLB (optionally in the ratio of about 0.01/10/10/1%);

Pyridoxal-phosphate, LID (optionally in the ratio of about 0.01/10%);

Pyridoxal-phosphate, DICLO(optionally in the ratio of about 0.05/10%);

Pyridoxal-phosphate, CAP, MT, CAMP (optionally in the ratio of about 0.05/0.0375%);

Pyridoxal-phosphate, CAP, MT, CAMP (optionally in the ratio of about 0.05/05%); and

Pyridoxal-phosphate, KEPF, KET, CAP (optionally in the ratio of about 0.05/10/6/0.075%);

h. an ointment formulation comprising L-Tyrosine, wherein the ointment formulation optionally is selected from the group consisting of L-Tyrosine, LID, GBP, KET, KEPF (optionally in the ratio of about 10/5/10/10/10%);

L-Tyrosine, GBP, KET, BAC (optionally in the ratio of about 10/10/10/4%);

L-Tyrosine GBP, KET, LID (optionally in the ratio of about 10/6/10/10%);

L-Tyrosine, GBP, KET, AM, BAC (optionally in the ratio of about 10/6/6/4/4%);

L-Tyrosine, KEPF (optionally in the ratio of about 10/10%);

L-Tyrosine, KEPF (optionally in the ratio of about 10/20%);

L-Tyrosine, KEPF, LID (optionally in the ratio of about 10/10/5%);

L-Tyrosine, KEPF, CLB(optionally in the ratio of about 10/20/2%);

L-Tyrosine, KEPF, UD, CLB (optionally in the ratio of about 10/20/5/2%);

L-Tyrosine, IBUF, KEPF, CLB (optionally in the ratio of about 10/10/10/1%);

L-Tyrosine, LID (optionally in the ratio of about 10/10%);

L-Tyrosine DICLO (optionally in the ratio of about 10/10%);

L-Tyrosine, CAP, MT, CAMP (optionally in the ratio of about 10/0.0375%);

L-Tyrosine, CAP, MT, CAMP (optionally in the ratio of about 10/05%); and

L-Tyrosine, KEPF, KET, CAP (optionally in the ratio of about 10/10/6/0.075%);

i. an ointment formulation comprising Synaptamine, wherein the ointment formulation optionally is selected from the group consisting of Synaptamine, LID, GBP, KET, KEPF (optionally in the ratio of about 10/5/10/10/10%);

Synaptamine, GBP, KET, BAC (optionally in the ratio of about 10/10/10/4%);

Synaptamine, GBP, KET, LID (optionally in the ratio of about 10/6/10/10%);

Synaptamine, GBP, KET, AM, BAC (optionally in the ratio of about 10/6/6/4/4%);

Synaptamine, KEPF (optionally in the ratio of about 10/10%);

Synaptamine, KEPF (optionally in the ratio of about 10/20%);

Synaptamine, KEPF, LID (optionally in the ratio of about 10/10/5%);

Synaptamine, KEPF, CLB (optionally in the ratio of about 10/20/2%);

Synaptamine, KEPF, LID, CLB (optionally in the ratio of about 10/20/5/2%);

Synaptamine, IBUF, KEPF, CLB (optionally in the ratio of about 10/10/10/1%);

Synaptamine, LID (optionally in the ratio of about 10/10%);

Synaptamine DICLO (optionally in the ratio of about 10/10%);

Synaptamine, CAP, MT, CAMP (optionally in the ratio of about 10/0.0375%);

Synaptamine, CAP, MT, CAMP (optionally in the ratio of about 10/05%); and

Synaptamine, KEPF, KET, CAP (optionally in the ratio of about 10/10/6/0.075%);

j. an ointment formulation comprising Kyotorphin, wherein the ointment formulation optionally is selected from the group consisting of Kyotorphin, Synaptamine, LID, GBP, KET, KEPF (optionally in the ratio of about 10/5/10/10/10%);

Kyotorphin, Synaptamine, GBP, KET, BAC (optionally in the ratio of about 10/10/10/4%);

Kyotorphin, Synaptamine, GBP, KET, LID (optionally in the ratio of about 10/6/10/10%);

Kyotorphin, Synaptamine, KEPF (optionally in the ratio of about 10/10%);

Kyotorphin, Synaptamine, KEPF (optionally in the ratio of about 10/20%);

Kyotorphin, Synaptamine, KEPF, LID (optionally in the ratio of about 10/10/5%);

Kyotorphin, Synaptamine, KEPF, CLB (optionally in the ratio of about 10/20/2%);

Kyotorphin, Synaptamine, KEPF, LID, CLB (optionally in the ratio of about 10/20/5/2%);

Kyotorphin, Synaptamine, IBUF, KEPF, CLB (optionally in the ratio of about 10/10/10/1%);

Kyotorphin, Synaptamine, LID (optionally in the ratio of about 10/10%);

Kyotorphin Synaptamine DICLO (optionally in the ratio of about 10/10%);

Kyotorphin, Synaptamine, CAP, MT, CAMP (optionally in the ratio of about 10/0.0375%);

Kyotorphin Synaptamine, CAP, MT, CAMP (optionally in the ratio of about 10/05%); and

Kyotorphin, Synaptamine KEPF, KET, CAP (optionally in the ratio of about 10/10/6/0.075%); and

k. an ointment formulation comprising Kyotorphin, wherein the ointment formulation optionally is selected from the group consisting of Kyotorphin, LID, GBP, KET, KEPF (optionally in the ratio of about 10/5/10/10/10%);

Kyotorphin, GBP, KET, BAC (optionally in the ratio of about 10/10/10/4%);

Kyotorphin, GBP, KET, LID (optionally in the ratio of about 10/6/10/10%);

Kyotorphin, GBP, KET, AM, BAC (optionally in the ratio of about 10/6/6/4/4%);

Kyotorphin KEPF (optionally in the ratio of about 10/10%);

Kyotorphin, KEPF (optionally in the ratio of about 10/20%);

Kyotorphin, KEPF, LID (optionally in the ratio of about 10/10/5%);

Kyotorphin KEPF, CLB (optionally in the ratio of about 10/20/2%);

Kyotorphin, KEPF, LID, CLB (optionally in the ratio of about 10/20/5/2%);

Kyotorphin IBUF, KEPF, CLB (optionally in the ratio of about 10/10/10/1%);

Kyotorphin, LID (optionally in the ratio of about 10/10%);

Kyotorphin DICLO (optionally in the ratio of about 10/10%);

Kyotorphin, CAP, MT, CAMP (optionally in the ratio of about 10/0.0375%);

Kyotorphin, CAP, MT, CAMP (optionally in the ratio of about 10/05%); and

Kyotorphin, KEPF, KET, CAP (optionally in the ratio of about 10/10/6/0.075%).