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Intravenous (Micro)nutrient Therapy- 증상, 질환중심으로 _ 김광민 Intravenous (Micro)nutrient Therapy - 증상, 질환중심으로 - 김광민 아주대병원가정의학교실 Intravenous Nutritional Therapy 비타민및미네랄등을이용하여혈액내로직접주입하여치료효과를내는방법 Case 40

1 Intravenous (Micro)nutrient Therapy- 증상, 질환중심으로 _ 김광민 Intravenous (Micro)nutrient Therapy - 증상, 질환중심으로 - 김광민 아주대병원가정의학교실 Intravenous Nutritional Therapy 비타민및미네랄등을이용하여혈액내로직접주입하여치료효과를내는방법 Case 40 세여자피로를주소를내원 2 년전부터잠을자고나도개운하지않고오후내내지속되어집안일을제대로못할정도 아침에자녀등교시아침식사준비를못할정도 설거지정도의가사일이후에도쉬어야함 전신근육통이동반 2 년전부터일반적인혈액검사 : 간기능, 갑상선기능검사, 빈혈, 혈당, 전해질, 류마티스인자, ESR 등검사상특이소견없음 위, 장내시경, 복부초음파등특이소견없음 우울증진단하에 SSRI 복용 : 호전없었음 Case Chronic fatigue syndrome 에합당한가? 어떻게할것인가? 기능의학적접근이도움이될것인가? - Hormonal (Cortisol, DHEA-s) - Tissue mineral analysis - Urine organic acid 분석등 IVNT(intravenous micronutritional therapy) 가도움이될것인가? History and IVNT (History of Myers Cocktail) John Myers a physician from Baltimore Myers 는 IV 치료성분에대한어떠한출판물이나자료를남기지않음. Myers 는 10-mL 주사기를사용하여 slow IV push 현재의제제는 Alan Gaby 가 Myers 가 1984 년사망이후에그의환자들을돌보면서만들어낸것임. 83

2 대한임상건강증진학회 2014 추계학술대회 The Myers Cocktail Magnesium chloride hexahydrate (20%) 5 ml Calcium gluconate (10%) 3 ml Hydroxocobalamin (1,000 mcg/ml) 1 ml Pyridoxine hydrochloride (100 mg/ml) 1 ml Dexpanthenol (250 mg/ml) 1 ml B-complex 100* 1 ml Vitamin C (500 mg/ml) 5 ml Sterile Water 20 ml B-Complex 100 of The Myers Cocktail B-Complex 100 contains the following per each ml: Thiamine HCl 100mg Riboflavin 2mg Pyridoxine HCl 2mg Panthenol 2mg Niacinamide 100mg Benxyl Alcolhol 2% The Myers Cocktail: biochemical pathways affected Kreb s cycle Detoxification pathways Metylation pathways Oxidative stress Oxidation phosphorylation Rationale for IV therapy 1. 소화효소의작용에의해일어날수있는영양소의변형을피하여직접적으로세포영양공급 2. 경구용제제의농도보다더높은세포내및세포외농도가가능 3. 즉각적인치료효과기대 4. INVT 가영양소결핍을해결할수도. Theoretical Basis for IVNT 영양소의정맥주사가경구용혹은근주용주사에의해서는획득될수없는혈중농도에도달할수있다. Theoretical Basis for IVNT 다양한영양소들이약물학적효과가나타나는데, 이는영양소의농도에따라다르다. 용법에따른 Viitamin C 농도 Administration Oral, 200mg/day Oral, 2500mg/day Oral, highest concentration IV 50g/day Serum concentration 1.2mg/dL 1.5mg/dL 9.3mg/dL 80mg/dL 예 ; 비타민 C 의항바이러스효과는 mg/dl 혈중농도에서나타나는데, 이는경구용에서는불가능하며, 정맥주사에서가능함. 84

3 Intravenous (Micro)nutrient Therapy- 증상, 질환중심으로 _ 김광민 Theoretical Basis for IVNT 세포내영양소결핍을교정할수있음. 적절한세포기능을유지하기위해영양소의높은세포내농도가필요 - 예 ) 마그네슘농도는심근세포내농도가세포외농도에비해 10 배이상높다. 마그네슘이온은혈관과기관지평활근육의이완을촉진 혈관경직성협심증혹은기관지천식의급성발작에서효과를나타내기도. Therapeutic Applications of IVMT Fatigue (including chronic fatigue syndrome) Fibromyalgia Chemical toxicity Asthma Migraines Acute muscle spasm Upper respiratory tract infections Chronic sinusitis Seasonal allergic rhinitis Cardiovascular disease Depression Narcotic withdrawal Chronic urticaria Common Ix of IVNT 다양한이유로전반적으로건강하지않다고느끼는환자 부신피로를포함한만성피로증후군 Fibromyalgia Asthma Migraines Acute muscle spasm Chemical toxicity secondary to any acute, chronic or intermittent exposure to chemicals 피로환자원인에따른접근방법 생리적피로 ; 생활의변화, 수면장애등 Medical illness( 간기능, 갑상선, 당뇨, 혈구검사, 염증, 암검사등 ) 정신적원인 ( 우울, 불안등 ) 스트레스 ( 정신적, 육체적 )-HRV 생활습관 ( 흡연, 음주, 운동부족 ) 기능이상 ; 남성호르몬, 부신호르몬, 모발미네랄검사, 소변유기산검사 기능의학에서의피로 Mitochondrial dysfunction - insufficient vitamins and minerals(cofactor) interfere with the Krebs cycle and oxidative phosphorylation Decreased level of Essential amino acids, neurotransmitter imbalance Adrenal fatigue Hormonal imbalance Infection, Dysbiosis, Ab-Ag response Immune dysregulation Deficiency in vitamin C 영양 피로의임상영양학적접근 : 조직미네랄검사 호르몬 중금속 ( 수은, 납등 ) 세포 ATP xxx 스트레스 피로면역기능이상근육통 조효소 ( 비타민, 미네랄 ) 마그네슘 망간 구리 / 아연 근육통, 불면, 불안 점심직후나른, 졸림 눈이침침, 야간시력저하 눈가떨림, 식은땀 두통 알러지 85

대한임상건강증진학회 2014 추계학술대회 TMA(Tissue Mineral Analysis) TMA (Tissue Mineral Analysis) 해석방법 미네랄결핍및과잉은혈액검사나소변검사에서보다조직미네랄검사 (TMA) 에서쉽게관찰 모발이가장적절 : 모근에서혈액의미네랄정보를받아, 다시혈액에반작용을하지않고하루에 0.

4 대한임상건강증진학회 2014 추계학술대회 TMA(Tissue Mineral Analysis) TMA (Tissue Mineral Analysis) 해석방법 미네랄결핍및과잉은혈액검사나소변검사에서보다조직미네랄검사 (TMA) 에서쉽게관찰 모발이가장적절 : 모근에서혈액의미네랄정보를받아, 다시혈액에반작용을하지않고하루에 0.3 mm씩자람 3 cm의모발 : 약 100 일치의미네랄에대한평균값질환이나질환으로이행하는과정의상태를파악 중금속의체내함유 Ca Mg Na K Cu Zn P Fe Mn Cr Se B Co Mo S - 모든미네랄의수치 (LEVEL) 은 mg% 따라서 (x 10 = ppm) - 영양미네랄및미량미네랄 ; 흰부분이정상범위정상범위보다높으면 HIGH 낮으면 LOW - 독성중금속은허용범위는흰부분많이축적될수록붉은색 - TMA 는인정비급여 ( 심평원공문, 수가 ; 2003 년 1 월 6 일 ) - 미국에서인가된검사기관 : CLIA 88, 45D 피로환자 ; Kreb s cycle 대사물로기능분석 소변유기산검사 Elevated levels of metabolic intermediates indicate a biochemical block just downstream of the elevated metabolite Blocks can be caused by - functional deficiencies of nutrient cofactors - inhibitors of enzymes(toxins, heavy metals) Fatigue: 병리적피로한달이상지속, 생활에지장을줄정도 Fatigue algorithm IVNT 주의사항 정상혈액 osmolarity mosm 병력청취신체검사 Lab: (-) (+) HRV, S-cortisol/DHEA, TMA, s-magnesium, Vit D, T-testo/LH, Vit B12/Folic acid, Urine organic acid (+) Other Medical condition Medication S/E Depression Sleep disorder 이상여부에따라치료여부결정 비타민 B12 는빠르게소변으로배설되어 IM 선호 Glutathione 및아미노산제제는 IVNT( 비타민 C) 와분리하여정주 86

5 Intravenous (Micro)nutrient Therapy- 증상, 질환중심으로 _ 김광민 사용하는 IV 제제 만성피로시 IVNT Kyominotin 2 ample Glycyrrhizinate 53 mg Glycine 400 mg Cysteine mg Magnesium Mg 2000 mg Beecom hexa 1 ample Nicotinamide 40mg B1 10mg B12 10μg B2 5.47mg B6 5mg Dexpanthenol 5.17mg Dutenol Dexpanthenol 500mg Thiamine Thiamine 50mg Bidoxin Pyridoxin 50mg Mega-C Vit C 10g Bivon 8 cc NaHCO 3 Glutathione Selenium Lipoic acid B ug MgCl 10 cc(2.0g) Pantothenic acid (B5) 2 cc (500mg) Pyridoxine(B6) 1 cc (50mg) Vitamin C 20 cc(10g) Bivon 8 cc B-complex 1 ample B1 50 mg Reduced Glutathione 10 cc(600mg): 따로 IV Glycyrrhizic acid 2 ample Selenium 0.5 ample Amino Acid Stages of Energy Production From Food Pyruvate Lactate Citrate cis-aconitate Vitamin C oxidative stress upon the mitochondria electron leakage which has been associated with fibromyalgia & CFS Malate Isocitrate Fumarate Succinate a-ketoglutarate Supports adrenal gland function Coenzyme for the conversion of L-dopa to NE: an important part of the physiologic stress response (shaded areas) = step requiring vitamin cofactor Vitamin B 1 (Thiamin) Physiologic function; Energy production, nucleic acid synthesis; require Mg! Conversion of Thiamin to Thiamin Pyrophosphate; active form- primary coenzymatic form B-complex Required for ATP production in glycolysis, TCA cycle and the electron transport chain Folic acid deficiency subclinical or clinical macrocytic anemia & fatigue Riboflavin (B 2 ) neuromuscular irritability(cramping/spasm) often accompanying CFS helpful for fatigue as it is required for production of the FADH molecule and energy production mitochondrial function by FADH production Vit B 5 required for adrenal hormone, metabolism of fatty acids, protein and CHO 87

6 대한임상건강증진학회 2014 추계학술대회 Muscle cramp( 쥐가나는경우 ) Muscle cramp 시 IVNT 5% D/W 200ml B comp 4 ample MgCl 10 cc(2.0g) Thiamine 50 mg B2 중요 Mg 필요 Vit B 6 Coenzyme for Mg and synergist of Mg Required coenzyme for hundreds of metabolic reactions Improve tingling, pain, weakness & numbness Vit B12 In Fatigue pts, - impaired transport of vit B 12 across the BBB, - accelerated breakdown of vit B 12 in the brain CFIDS Chronicle 1997(Winter):57 Recommended I.M in the morning d/t excitatory effect of vit B 12 CFIDS Chronicle 1999(Nov/Dec):14-16 Vit B12 Cyanocobalamine: poisoning 문제로잘사용되지않음 Hydroxocobalamine: bioavailability 가매우높음 Methylcobalamine: Methylation 에사용됨 Magnesium Major role in reactions involving ATP, DNA & RNA Many enzymes (over 400) require Mg Required for the shuttling of potassium intracellularly Often deficient in fibromyalgia 45% low at sites of tenderness in pts with fibromyalgia In balance with Ca - between 2:1 and 1:2 good to reduce intracellular Ca & abnormal calcification Arthritis Rheum 1994;37:

7 Intravenous (Micro)nutrient Therapy- 증상, 질환중심으로 _ 김광민 Magnesium Highly concentrated in the adrenal gland Required in the TCA cycle as Mg for energy production Sx of CFS are quite similar to Mg deficiency IV Mg rapid resolution of chronic muscle pain Glutathione Synthesized from amino acids - L-cysteine, L-glutamate, and glycine Sulfhydryl group of cysteine is a proton donor and is responsible for its biological activity Protects cells from ROS, free radicals and peroxides Helps regulate blood sugar balance Magnes Trace Elem 1990;9:333 Glutathione for fatigue Major endogenous antioxidant produced by cells. Maintains reduced state of other antioxidants - Vitamin C & E Detoxifies many xenobiotics Maintains numerous metabolic and biochemical reactions - DNA synthesis and repair - Protein synthesis - Prostaglandin synthesis - Amino acid transport - Enzyme activation Glycyrrhizic acid Component of licorice root Reduce AST, ALT in serum Inhibits immune-mediated cytotoxicity against hepatocytes and NF-kappa B powerful antiviral effects particularly against hepatitis C Lower estrogen, raise progesterone aldosterone-like effects Licorice root >3g/d or glycyrrhizin acid >100mg/d, >6 weeks Na and water retention, HTN, hypokalemia, renin-aldosterone inhibition BP, electrolyte monitoring Recommend potassium intake Glycyrrhizic acid Supports the adrenal gland cortisol availability Arzneimittelforschung 1979;2994): Clin Sci(Colch)2002;102: Effects of glucocorticoids & mineralocorticoids by slowing the rate of their catabolism Endocrinol Jpn 1990;37: Arzneimittelforschung 1979;2994): J Clin Endocrinol Metab 1956;16: Endocrinol Jpn 1957;4:

대한임상건강증진학회 2014 추계학술대회 부신기능저하시 피로 특징 TMA 상 Na/Mg < 4.

5%) Adrenal Function 과 관련된 IVNT Glycyrrhizic acid Subnormal 24-hour urinary excretion in CFS pts methionine, phenylalanine, isoleucine,

months in 15 of 25 pts with CFS Magnesium J Appl Nutr 1994;46(3):74-78 Amino Acids (8.

synthesis improve stress-associated declines in noradrenaline and performance Phenylalanine Precursor to tyrosine, depamine, L-dopa,

8 대한임상건강증진학회 2014 추계학술대회 부신기능저하시 피로 특징 TMA 상 Na/Mg < 4.0:1 혈액, 타액 검사상 코티졸 감소 아침에 개운하지 않으며: arousal 효과 감정변화(우울과 불안) 심함 저녁 7-8 시경이 컨디션이 가장 좋은 특징을 보임 코티졸 Amino Acids (8.5%) Adrenal Function 과 관련된 IVNT Glycyrrhizic acid Subnormal 24-hour urinary excretion in CFS pts methionine, phenylalanine, isoleucine, lysine, tryptophan, valine, leucine Pantothenic acid J Nutr Med 1991;2: Vitamin C Significant clinical improvement after 3 months in 15 of 25 pts with CFS Magnesium J Appl Nutr 1994;46(3):74-78 Amino Acids (8.5%) Required for detoxification, immune function Tyrosine required for the synthesis of thyroid hormone enhance dopamine, catecholamine synthesis improve stress-associated declines in noradrenaline and performance Phenylalanine Precursor to tyrosine, depamine, L-dopa, NE, epi All required for a proper stress response 90 Important Amino Acids for fatigue BCAA s; essential to all biologic functions Glutamine; Needed for Muscle, GUT health Tryptophan; Precursor to serotonin Arginine; promotes healthy NO and IGF-1 levels. vasodilatory and antihypertensive effects in IV.

Intravenous (Micro)nutrient Therapy- 증상, 질환중심으로 _ 김광민 바이러스질환에도움이되는 IVNT Antiviral activity 과 Adrenal gland function - Vitmain C - Glycyrrhizic acid - Pantothenic acid - Magnesium 도움이되는대표적인 Antiviral

9 Intravenous (Micro)nutrient Therapy- 증상, 질환중심으로 _ 김광민 바이러스질환에도움이되는 IVNT Antiviral activity 과 Adrenal gland function - Vitmain C - Glycyrrhizic acid - Pantothenic acid - Magnesium 도움이되는대표적인 Antiviral Diseases - Herpes zoster - Facial palsy - Common Cold - Influenza Vitamin C Antiviral effect of vitamin C; mg/dl - level achievable with IV but not oral therapy Pharmacological activities of Glycyrrhizic acid Dose dependent inhibition of GL against HCV 3a genotype Antioxidative, anti-inflammatory, antiulcerous, antidotal, antiallergic, antiviral, immunomodulating, hepatoprotective, and cardioprotective properties Journal of Translational Medicine :112 Dose dependent inhibition of GL against HCV core gene IVNT cycle 치료의원인및환자의상태에따라서 일반적으로 1 회 /1 week 달 1 회 /2 week 달 1 회 /1 month 달 2 주 1 회부터는경구용제제복용 2-4 개월에필요하면 Mg, Vit D, Cortisol, DHEA-S 검사 6 개월에 Mg, Vit D, Cortisol, DHEA-S, 모발미네랄검사등진행하여증상및검사소견비교하여치료중단및지속여부결정 Journal of Translational Medicine :112 91

10 대한임상건강증진학회 2014 추계학술대회 만성피로시 IVNT MgCl 10 cc(2.0g) Pantothenic acid (B5) 2 cc (500mg) Pyridoxine(B6) 1 cc (50mg) Vitamin C 20 cc(10g) Bivon 8 cc B-complex 1 ample B1 50 mg Reduced Glutathione 10 cc(600mg): 따로 IV Glycyrrhizic acid 2 ample Selenium 0.5 ample Amino Acid Placenta Extract Summary IVNT appears promising for treatment of Fatigue, Myalgia, Migraine sysmptoms Use of IVNT is effective at present, although still over the line of evidence Future efforts will need to move further upstream 92

Lehninger Principles of Biochemistry 5/e

David L. Nelson and Michael M. Cox LEHNINGER PRINCIPLES OF BIOCHEMISTRY Fifth Edition CHAPTER 18 Amino Acid Oxidation and the Production of Urea 2008 W. H. Freeman and Company Dietary proteins Synthesis