Comparison & Integration of Western and Eastern Medicine Jing Liu, PhD, Lic.Ac 2011 A copy right is reserved for the materials in the following presentation Integrated Medicine Western Medicine + TCM + Natural Medicine ( Nutrition, diet, herbs, natural therapies in the world) 11/10/10 Jing Liu 3 Natural Medicine 从学科分类学的角度审视,一门学科不应是有地区属性的医学科学不 应分属于西、东方,应该统一于现代医学范畴内。中医药学应属于现 代医学的一个分支学科. 从科学的定义上考虑,在中医药学最终能够被现代医学接受之前,将 中医纳入到自然医学体系。 自然医学将逐步取代替代医学/中西医结合等名称而成为现代医学家族 的( 而非西方医学)中的一个重要学术分支。 在自然医学的范畴中,国家的属性将被医学体系的自然性和科学性逐 渐取代,成为世界医学界都容易被接受的一门医学 Content Fatigue - Hormone Balance Inflammation Pain Comments on acupuncture clinical trails: Placebo, Specificity of acupoints Cause of Fatigue Insomnia Heart - kidney disharmony Hormone dysfunction Kidney deficiency Gut inflammatory status Spleen: Dampness / phlegm Yin & Yang Insomnia treatment WM Sedative-Hypnotics or antipsychotics Adverse reactions: drowsiness, weakness, pseudodepression in the morning EM Encouraging Yang energy in the morning and nourishing Ying in evening Yang encouraging : Yin nourishing: 11/10/10 Jing Liu 7 Yin & Yang Theory and Sleep A general principle in traditional Chinese Medicine (TCM) practice Morning Yang Time: adrenal, thyroid hormone awake and rise to peak energetic, active Evening and Night Yin time: melatonin and serotonin dominant –calm and sound sleep Higher Yang in the morning, Deeper Yin control in evening and night, better quality of sleep 11/10/10 Jing Liu 8 Sleep and Hormone Balance Insomnia - Cortisol Dysfunction Syndrome Fatigue Depression Insomnia Irritability/. Anxiety Sweets craving Poor concentration Headache Allergy Elevated sympathetic nerve tone and decreased cortisol = Heart Kidney Disharmony 心肾不交 ? Insomnia Treatment Basic Formula (1) Kidney strengthening Mai Wei Di Huang Tang 麦味地黄 Add: Ginseng人参, Royal jelly蜂王浆, Adrenal hormone promoting: Shan Zhu Yu山茱萸, Shu Di Huang熟地黄 Estrogenic phytohormone: Shan Yao山药(tocopherol, Coenzyme Q9, Cyloartenol, 1- feruloyl glycerol, hydro-Q9, chromene) Insomnia Treatment Basic Formula (2) 酸枣仁汤 酸枣仁 川芎 Anti-inflammatory 茯苓 Reduce edema 知母 Anti-sympathetic, Anti-inflammatory 甘草 Anti-inflammatory, Detox Add: hehuanhua合欢花, lianzixin莲子芯,baishao 白芍 Causes of Fatigue Heart: Insomnia Kidney: Hormone Dysfunction ( HPTA Axis) Spleen: Gastrointestinal Dysfunction Fatigue and Hormone HPA Axis The current evidence supports the following factors of HPTA axis dysfunction in patients related with chronic fatigue syndrome (CFS): Mild hypocortisolism Attenuated diurnal variation of cortisol Blunted HPTA axis responsiveness to body need. hypothyroid function Imbalanced sexual hormones Adrenal Hormone Synthesis Adrenal Hormone Synthesis Estrogen Family Adrenal Dysfunction / Fatigue Adrenal glands are unable to keep pace with the demands of perpetual stress. Stress signals > cortex > limbic system > sympathetic nerve > adrenal gland > cortisol release/thyroid hormone The gland can't produce quite enough of the hormones our mind-body need. Existing blood tests, aren't sensitive enough to detect the decline in adrenal function: cortisol panel test The Symptoms of Adrenal Fatigue Qi & Yin Deficiency Fatigue, mostly Midday Fatigue Unexplained Weight loss Reduced tolerance for stress Insomnia Anxiety Craving for sweets and salty foods Body hair loss Body aches Depression Low Cortisone Syndrome Above symptoms plus: Increased susceptibility to infections Allergies to things you were never allergic to before Chemical sensitivities (Hyper Chemical Sensitivity) Herbs for Adrenal Dysfunction Panax Ginseng 人参 Elwutherococcus 西伯利亚人参 Rhodiola 红景天 Yin Yang Huo 淫羊藿 Shan zhu yu 山茱萸 Ocimum sanctum ( holy basil) 圣罗勒 Withania 睡茄 Glycyrrhiza 甘草 (Hypotension) Other herbs for Kidney Yin/Yang deficiency Treatment of Adrenal Fatigue Progesterone cream Iodine / tyrosine Phosphorylated serine / He Shou Wu 何首乌 Pregnenolone / Cortisol Melatonin at bed time Hypothyroidism (1) Qi & Yang Deficiency Fatigue Shortness of breath with a shallow and slow respiratory pattern Low basal body temperature, Cold intolerance Thyroid-Related Depression slow heart rate Sluggish reflexes Constipation Poor muscle tone (muscle hypotonia) Slow speech and a hoarse, breaking voice Depression Kidney deficiency Decreased libido Hair loss Lower renal function with decreased glomerular filtration rate Impaired memory Abnormal menstrual cycles Thin, brittle fingernails Female infertility Hypothyroidism (2) Spleen deficiency Weight gain and water retention Enlarged tongue Yellowing of skin due to impaired conversion of beta-carotene to vitamin A Impaired Puffy face, hands and feet (Non-specific Edema?) Impaired cognitive function (brain fog) Yin & Blood deficiency Dry, itchy skin Decreased sweating Others Elevated serum cholesterol Muscle cramps and joint pain Hyperprolactinemia and galactorrhea Wilson's Temperature Syndrome Temperature lower than 98.60F Hypothyroidism symptoms with normal T3, T4 Typically brought on by stress often exist with chronic fatigue syndrome, fibromyalgia’ Improved by treatment of T3 or herbs / supplements; not respond to T4 treatment Causes of Hypothyroid Syndrome Iodine deficiency Stress Hushimoto disease ( chronic lymphocytic thyroiditis), 25% lithium-based mood stabilizers, usually used to treat bipolar disorder (previously known as manic depression) Congenital hypothyroidism is very rare accounting for approximately 0.2‰ Thyroid Hormone 90% T3 (effects fast, short term) 10% T4 (effects slow, long term) T3 is only form of thyroid hormone to supply energy to heart from breaking down fat Over dose of T3 cause cardiac overloading Conversion of T3 or RT3 Conversion of T4 to T3 Promoters (1) Kelp (iodine, Iron), selenium Zinc, potassium, cupper High protein diet Vitamin A, E, C, B2, B3, B6, B12 Growth Hormone Testosterone Ashwaganda (India herb) Inability to convert T4 to T3 Excessive alcohol Low protein/fat diet Too much cruciferous vegetables Walnuts Low T3 / High reverse T3 Promoters Stress - epinephrine / NE, cortisol Free radicals Aging Fasting Diabetes Toxic metal exposure Inflammation-elevated inflammatory factors: IL-6, TNFalpha, IFN-2 Iodine Deficiency 88% America women are in iodine deficiency. Low iodine cause hyperestrogenic state and higher free estrogen level up to 80 to 90%, normal is 40 to 60%. When Iodine is enriched, the estrogen receptor activity in the breast is reduced. Iodine promote apoptosis and disrupt proliferation Low iodine cause fibrocystic breast; Effective therapy (82%) in treating fibrocystic breast disease and prevent breast cancer TCM: Hai Zao, Kun Bu 海藻,昆布 Iodine Deficiency Causes of Iodine Deficiency Diet in shortage of iodine Iodine Taken Up: Thyroid: 6mg; breasts: 5mg /day; other tissues: 2mg/day Japanese women: 13.8mg daily, lowest in breast cancer Diet high in pasta/bread containing bromide (bind to iodine receptor) Fluoride use (inhibiting iodine binding Vegan and vegetarian diet Drugs for T3/T4 replacement T3: Liothyronine, Triiodothyronine T4: Levothyroxine (Synthroid) Transfom to be T3, but take up to 8 weeks to reach the required level of T3. Armour® a naturally derived from porcine thyroid glands. (T3 liothyronine is 4x as potent as T4 levothyroxine; so 38 mcg T4and 9 mcg T3 per grain of thyroid. Thyroid Hormone Replacement Failure After increase dosage still feel fatigue: Magnesium deficiency Adrenal deficiency Overdose Poor absorption from unhealthy gut Side Effects of T3 Therapy Fluid pretension Achiness Jitteriness Irritability Dull headache Increased heart rate Can not be used for severe Adrenal or cardiac deficiency Herbs for Thyroid Function Huang Qi黄芪 Huang Qi Wu Wu Tang黄芪五物汤 Or add: Xiao Chai Hu Tang小柴胡汤, in case of autoimmune Prolonged hypothyroidism cause adrenal fatigue Adrenal: Ying Yang Huo 淫羊藿, Shan Zhu Yu山茱萸 When the herbs not effective enough, add T3, to reduce the dose of T3 and reduce the side effect of T3 Natural Supplements for Thyroid Function Guggul (Commiphora mukul) increase iodine intake and thyroid hormone production, enhance thyroid perocidase enzymes Seaweed (algae) : Kelp (kun Bu) bladder wrack fucus vesiculosus (best antioxidant among seaweeds) Seaweed contain diiodothyoinine (DIT), which may promote thyroid function Zinc, Selenium Blue Flag - potent detoxifier of thyroid Improvement usually occurs within 3 to 4 weeks Hushimoto’s Disease Reduce autoimmune response and inflammation Xiao Chai Hu Tang 小柴胡汤 Curcumin Boswellia Lycopus virginicus(lycopus lucidus 泽兰) inhibit iodine metabolism, inhibits release of thyroxine from thyroid, binds with TSH, decrease pulse and BP 95% improvement rate, officially recognized in Germany as prescription Rosemary extract (迷 迭香100:1), reduce antibody Hormone: Progesterone Produced mainly in ovary, little in adrenal gland; Increase 100x during pregnancy Enhance: thyroid function, apoptosis, estrogen sensitivity, brain cell growth in fetus Decrease: breast cell growth, breast cancer, atherosclerosis, Decrease Brain degeneration, neuro-blastoma, MS; antidepression Burn fat for energy; hair growth; Progestins are NOT equal to progesterone Herbs for Progesterone Juglans regia (England Walnut 核桃), progesterone detected Progesterone-like steroids in Dioscorea mexicana of yam family native to Mexico, containing steroid diosgenin converting into progesterone. Diosgenin and progesterone found in other Dioscorea species. Dioscorea pseudojaponica from Taiwan, containing saponins —converted to diosgenin -> progesterone. Other Dioscorea species: Dioscorea villosa andDioscorea polygonoides. Dioscorea villosa contains 3.5% diosgenin. Dioscorea polygonoides contain 2.64% Dioscorea family: Shan Yao山药, Bi Xie, Chuan Shan Long穿山龙, Shan Ci Gu山慈姑 I Sheng Ma 升麻 Maca Fu Pen Zi 覆盆子 Hormons: Estradiol(E2) Neuro-protective Breast cancer promoting Cell proliferation with alveoli formation (hyperplasia) and even cyst formation Effects of Estrogen Therapy Prevent osteoporosis Decrease LDL and increase HDL Increase blood pressure, triglyceride Gallstone Elevated liver enzyme Increase carbohydrate craving Decrease thyroid function by increasing binding thyroid binding globulin Estrogen Balance In the 1960s and 70s Dr. Henry Lemon concluded: Estrogen Quotient EQ=E3/E1+E2 EQ<1: high risk for breast cancer EQ>1.5: low risk for breast cancer Hormone: Estriol Anti-inflammation Promote shift from T helper (Th) 1 to Th2 Reduce autoimmune disease Prevent osteoporosis Breast caner protection Menopause improvement 92 Don't seem to increase risk of breast cancer Estriol binds to estrogen receptors with much weaker activity, competing stronger estradiol binding to receptors - protective against breast cancer Estrogen Dominance Fatigue Hypothyroidism by decrease conversion of T4 to T3 Decreased sex drive Depression / anxiety / Migraines / Insomnia Memory loss or foggy thinking Mood swings / Memory loss or foggy thinking Weight gain secondary to insulin resistance / Fat gain PMS / Menstrual disturbances--irregular and heavy bleeding. Bone loss / Hair Loss Breast cancer / Fibrocystic breasts / Uterine cancer / fibroids Water retention, bloating. Tendency of autoimmune disorder Correction: Progesterone therapy Estrogen Dominance After menopause, Progesterone decreases by over 99% from its original youthful baseline levels; while estrogen production only decreases by about 40%. New research show that almost all the uncomfortable symptoms of PMS and of Menopause are actually caused by low progesterone levels in the body. Breast Cancer prevention Bio-identical Estrogen therapy E3:E2 = 4:1 DIP D Vitamin D deficiency Iodine deficiency P Progesterone deficiency Hormone: Testosterone Testosterone Improve insulin resistance, belly fat Improve: sleep, vitality, libido/orgasm/arousal Not necessary cause prostate cancer Herbs:Yin Yang Huo淫羊藿, Rou Cong Rong肉苁蓉, Lu Rong鹿茸, Ren Shen人参 Hormone: DHEA the first anti-aging hormone Improve motivation, well being, memory, libido/orgasm Anti-atherosclerosis Antidiabetic Anti-inflammatory Antiosteoporotic Anti-senility Reduce fat Protect thymus and immune function 50mg daily anti-age without significant side effects Fatigue Fatigue and GI dysfunctiion / Candida Symptoms of Candia (1) fatigue concentration/focus memory problems painful joints, muscle aches unrefreshing sleep white coated tongue chronic sinusitis Diarrhea or chronic constipation headaches including migraines visual blurring, sensitivity to light, eye pain Depression, irritability, anxiety sensitivity to heat/cold alcohol intolerance gluten intolerance Symptoms of Candia (2) Irritable bowel numbness/tingling in the face or extremities dryness of mouth and eyes menstrual problems (PMS/endometriosis) recurrent yeast infections skin rashes, dry/flaking skin Eczema, dermatitis, acne jock and rectal itching chronic athlete's foot, toenail and fingernail fungus ringing in the ears (tinnitus) allergies sensitivity to noise/sounds,foods,chemicals feeling in a fog muscle weakness jerky-leg syndrome low sex drive Anti-Candida Herbs Cinammon Grapefruit seed extract Olive leaf extract Garlic extract Berbering, Goldenseal Oregano leaf extract Pau d’arco Zinc Coconut oil Candex (cellulase enzymes) Introduction: Inflammation Normal inflammation is a necessary protective response to harmful stimuli to the body. Prolonged or excessive inflammation is related pathological status including infection, autoimmune disorders, atherosclerosis, Alzheimer's, autism, arthritis and even cancer Inflammation Process Eicosanoid Cyclooxygenase Pathway Pathogen IL-1, TNF-a, PDGF, IFNs, Tyrosine Kinase chemokines proliferation inflammation Adhesion penetration hypoxia, superoxide, NO, free radical AA COX2 cancer inflammation PGE2 Eicosanoid Synthesis Prostaglandin/Inflammation Formation Pathway Eicosanoid Synthesis Prostaglandins and related compounds are collectively known as eicosanoids. Most are produced from arachidonic acid (AA) Step one: Release of AA from membrane phospholipids by phospholipase A2(PLA2). Step Two: AA is metabolized by COX enzymes to be prostaglandin E2 (PGE2), or Thromboxin (TXA2) or prostacyclin (PGI2), AA also metabolized by lipoxygenase or cytochrome P450 to be leukotrienes Ecosanoid considered "local hormones." participating in intercellular signaling, Role of Ecosanoid inflammation fever regulation of blood pressure blood clotting immune system modulation control of reproductive processes & tissue growth regulation of sleep/wake cycle. Ecosanoid Inhibitors Corticosteroids are anti-inflammatory from preventing PL A2 expression, reducing AA release. Stress – adrenal fatigue – cortisol exhaustion - inflammation COX-2 is stimulated by growth factors, cytokines, and endotoxins. Attempts have been made to develop drugs that inhibit: Phospholipase A2 / AA / COX for treating inflammatory diseases Inflammation Inflammation exist in many diseases: cancer, autoimmune disorders, infections, et al. WM COX-2 inhibitor (Vioxx, Celebrex) Adverse reactions: PGI2 inhibition – inner membrane of blood vessel damage leading stomach ulcer, kidney failure, cardiac attack EM Natural COX 2 inhibitor: Curcumin, turmeric姜黄, coptis黄连, berberine, Paeonia Latiflora芍药, Boswellia乳香 No obvious PG I 2 inhibition; Only benefit to heart 11/10/10 Jing Liu 61 COX-2 COX-2 levels increase in inflammatory diseases such as arthritis. COX-2 expression is increased in some cancer cells. Angiogenesis, essential to tumor growth, requires COX-2. Over expression of COX-2 leads to expression of VEGF (vascular endothelial growth factor). Regular use of NSAIDs has been shown to decrease the risk of developing colorectal cancer. Anti-inflammatory Therapy Side effects & Limitations of Chemical Drugs Naproxen Naproxen, trade name Alevea, a nonsteroidal anti-inflammatory drugs (NSAID) ibprofen, indomethacin and ketoprofen. Common side effects Constipation; diarrhea; dizziness; drowsiness; gas; headache; heartburn; nausea; stomach upset; stuffy nose. Severe side effects rash; hives; itching; swelling of the mouth, face, lips, or tongue; wheezing); bloody stools; change in the amount of urine produced; chest tightness or pain; confusion; dark urine; depression; fainting; fast or irregular heartbeat; fever, chills, or persistent sore throat; loss of appetite; mental or mood changes; numbness of arm or leg; onesided weakness; pale stools; red, swollen, blistered, or peeling skin; ringing in ears; seizures; severe headache or dizziness; stomach pain, nausea, vomiting or bleeding; shortness of breath; weight gain; swelling of the hands, legs, or feet; bruising or bleeding; joint or muscle pain; tiredness or weakness; vision or speech changes; grounds; yellowing skin or eyes. This is not a complete list of all side effects that may occur. COX Inhibitors Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and derivatives of ibuprofen: a. Inhibit COX to form prostaglandins involved inflammation, pain. b. Inhibit blood clotting by blocking TXA2 c. block AA enters COX active site. Most NSAIDs inhibit both COX I & COX II. Selective COX-2 inhibitors have been developed, e.g., Celebrex and Vioxx. COX-2 inhibitors are less likely to cause gastric toxicity compared with NSAIDs that block COX-1. Inflammation and Endothelial Dysfunction to Microvascular Dysfunction Endothelial dysfunction is integral to the pathogenesis of many disorders: Atherosclerosis Autoimmune disorders Inflammation Infection Trauma Arterial Wall Anatomy Endothelium of Blood Vessels Vascular Endothelial Mediators Thromboxane A2 - TXA2 Stimulates blood platelet aggregation, essential to role of platelets in blood clotting. Aspirin inhibit TXA2 formation in blood platelets. This effect of aspirin is long-lived, 7 days, because platelets lack a nucleus and do not make new enzyme. Leukotrienes Leukotrienes produce inflammation in: Blood vessel walls as part of the pathology of atherosclerosis. Bronchioles causing asthmatic constriction and asthma. Anti-asthma medications include: Zyflo (zileuton): inhibitors of 5-Lipoxygenase Singulair (montelukast) & Accolate (zafirlukast): block leukotriene-receptor interactions. Natural COX-2 Inhibitors Huangqin黄芩 was found to have COX-2 inhibitory properties in China, Spain, Korea, Canada and United States Ginger姜 is a strong anti-inflammatory herb. Studies indicate that ginger is a safe COX- 2 and COX-1 modulator Scientists in the USA, Sweden, Taiwan and Germany have confirmed that green tea is a high active COX-2 inhibitor. The chemical ingredients, salicylic acid and polyphenols, including EGCG, in green tea are effective cancer antagonists. Turmeric or curcuma longa The anti-COX-2 effect of turmeric was discovered by Vanderbilt University researchers. Cornell University in New York and the University of Leicester in England. The active anti-inflammation component curcumin is about 50% as effective as cortisone. The purified form of 95% curcuminoids per dose is the best anti-inflammatory effects. A number of publications have shown the anti-cancer effects of turmeric in in vitro and in vivo. Natural COX-2 Inhibitors Curcumin and capsaicin significantly lowered lysosomal enzymes from macrophages in animals Macrophages from rats secreted less PG E2, leukotrienes B4 and C4 and AA. Curcumin and capsaicin lowered eicosanoids and AA in macrophage lipids. Curcumin and capsaicin can lower secretary functions of macrophages in a beneficial manner. Natural Anti-inflammation/COX-2 Agents Drynaria fortunei Extracts of Drynaria fortunei (Gu Sui Bu): significant inhibition of carrageenan-induced paw oedema and granuloma formation in rats, almost comparable to that caused by indomethacin. Df significantly attenuated formalin-induced pain and acetic acid-induced writhing episodes in mice. Clinical trial: significant effects for arthritis pain, joint function and osteoporosis without significant side effects CONCLUSION: potent anti-inflammatory agent for alleviating painful inflammatory conditions of osteoarthritis. The herbal formula for arthritis: Gu Sui Bu, Fang Feng, Cuan Duan, Zhi Mu, Jing Jie + Huang Qi Wu Wu Tang Herbs with COX-2 Inhibitory Effects green tea, ginger, grape seed, Holy basil, oregano, rosemary and willow bark Giardina C褐茸藻, Stylopine from chelidonium majus白屈菜, Berbarine/Huanglian黄连, ginger, ginsenoside人参皂甙 Rh1, grape seed葡萄, Salvia miltiorrhiza 丹参, fevervew, scutellaria黄 芩, phellodendron amurense黄柏, carthamus tinctorius红花, nettle leaf荨麻,willow bark柳树 皮 Anti COX Agents - Antioxidants The oxygen burst in the inflammatory status generate excessive amount of reactive oxygen species (ROS) . Reactive neutrophil activity in the process is a principle source of ROS. Inflammatory responses can be suppressed by the application of ROS scavenger, superoxide dismutase (SOD) and antioxidants. Many antioxidants possess COX-2 inhibiting effects: Polyphenol and catechin in green tea Flavonoid and ursolic acid in many herbs linoleic acid, melatonin, IFN-βin our bodies physiologically inhibitory COX-2 effect Omega-3: Role in Anti-inflammation ω-3, mainly DHA and EPA, can effectively inhibit COX mediated AA metabolism and PGE2inflammation/cancer Plant ω-3 shows inhibitory effect on inflammation and cancer Acupuncture Mechanism: Pain / Inflammation / immune Pain Inflammatory Immune Cholinergic suppression: Sensory nerves Parasympathetic nerve endings release acetylcholine (ACh), suppress release Hypothalamus Anti-inflammatory output via CNS TNF-a, IL-1β in brain Neuroimmunology modulation Inflammation Role of Arachidonic Acid High arachidonic acid consumption (Omega-6) is not advised for individuals with a history of inflammatory disease, it may counter the anti-inflammatory effects of omega-3 fatty acid supplementation. Inflammation Omega-3 : Omega6 Inflammation Omega-3 : Omega6 Patients with autism had significantly higher Omega 6 in RBC membranes compared to higher Omega 3 in healthy people Significantly reduced levels of ARA /EPA ratio in RBC polar lipids, when supplemented with EPA-rich fish oils By taken EPA supplements, significantly reduced PLA2 concentrations Natural Anti-inflammation/COX-2 Agents Curcuma longa L Positive effect on neurogenesis in hippocampus by increasing brain-derived neurotrophic factor(BDNF) Improving stress, depression, a selective monoamine oxidase inhibitor (MAOI) Clinical trials: Alzheimer's disease. Anti-inflammatary Supplements Feverfew (菊蒿) Holy basil (圣罗勒) Nettle Leaf(荨麻) Oregano Rosemay(迷迭香) Boswellia Natural Anti-inflammation Agents: Antioxidants The oxygen burst in the inflammatory status generate excessive amount of reactive oxygen species (ROS) . Reactive neutrophil activity in the process is a principle source of ROS. Inflammatory responses can be suppressed by the application of ROS scavenger, superoxide dismutase (SOD) and antioxidants. Natural Anti-inflammation Agents: Antioxidants Many antioxidants possess COX-2 inhibiting effects. Phenol and flavonoid compounds in many herbs: polyphenol and catechin in green tea, ginkgo biloba, soy, etc. Some important antioxidants/anti-inflammation chemicals produced in the body: Glutathione,, melatonin, pyruvate, IFN-b, and SOD. Natural Anti-inflammation Agents from diet: Berries Berries Blueberries, raspberries, strawberries: antiinflammatory Blackberries and blueberries are especially great. Natural Anti-inflammation Agents from diet: Omega-3 -3, mainly DHA and EPA, can effectively inhibit COX mediated AA metabolism and PGE-2 inducible inflammation/cancer. High -6 low -3 diet favor inflammation flax seed oil, walnut, pumpkin seed are rich in 3 but in shortage of DHA. Botanical -3 may anti-inflammation by inhibiting -6 through competing delta desaturase 6. Root of Inflammation Broad-spectrum antibiotics kill good bacteria in gut, leading to leaky gut syndrome - large molecules get through. London’s Royal Free Hospital studied 60 autistic children: many more intestinal lesions than nonautistic children In fact, over 90% of autistic children had chronically inflamed guts. Root of Diseases - Inflammation Root of Inflammation - GI microflara Alzheimer, Autism Chronic lung/bronchus infection Arthrosclerosis Sinus infection/allergy Chronic Fatigue syndrome Fibromyagia Autoimmune disorders: MS Lupus Colitis Arthritis Acupuncture Pain 11/10/10 Jing Liu 90 Acupuncture for pain Indication A wide range of pain conditions, such as postoperative pain, carpal tunnel syndrome, fibromyalgia, headache, low-back pain, menstrual cramps, myofascial pain, osteoarthritis, and tennis elbow. Doctors from three medical schools published on New England Journal of Medicine Conclusion: acupuncture is an effective means for treating lower back pain, based partly on a recent study of 6,359 patients published 11/10/10 Jing Liu 91 Acupuncture Clinical Trail Osteoarthritis 20millions people with osteoarthritis No satisfied pharmaceutical drugs COX-2 inhibitor may cause heart, kidney stomach damage Phase III radomized controlled clinical trail at Maryland School of Medicine in 2006 570 participants with moderate and severe pain Results: significantly improve knee pain and function Acupuncture for pain Significant, Mechanism New branch of therapy in clinical medicine: Trans-cutaneous Intervention therapy A lot of augments on the meridian theory At least, most parts of acupuncture theory and practice can be explained by the modern neurology or neurochemistry. CNS endorphin, serotonin, dopamine modulation, opioid receptor stimulation Neural segmental analgesia (spinal cord) Local anti-inflammatory cytokine, microcirculation promotion 11/10/10 Jing Liu 93 Specificity of Acupuncture points Brain: Overlapped, relatively less specificity Spinal cord: neural segmentation distribution, relatively specificity, with connection Local: chemicals, neuro-muscle-tendon effects, specific Acupuncture Evidences in neurochemistry In the mid 1970s, Mayer and his colleagues revealed that acupuncture led to a significant increase in the endogenous endorphin production and the effect of acupuncture can be blocked by the opioid receptor antagonist naloxone 11/10/10 Jing Liu 95 Acupuncture Evidences in neurochemistry A large body of evidence indicates that acupuncture significantly affects the production and release of neurotransmitters including epinephrine, norepinephrine, dopamine, and 5-hydroxytryptamine Stress-induced increases in norepinephrine, dopamine, and corticosterone were inhibited after EA, EA effects on the release of neurotransmitters are likely to be mediated through endogenous opioids. EA at different frequencies (2, 10, or 100 Hz) elicited the analgesic effects and such effects could be at least partially blocked by a serotonin receptor antagonist 11/10/10 Jing Liu 96 Acupuncture Neural segmental analgesia 11/10/10 97 穴位特异性与神经阶段 内脏与体表相连:白交通支 Acupuncture Pain management and muscle relaxation Acute pain Muscle spasm Chronic pain Muscle spasm - shortening - fibrosis -hardening Trigger Point – neural-muscle cycle Pain signals from the muscles and joints cause changes in the central nervous system (CNS) that in turn causes changes in the nerves affecting muscles and joints inducing perception of perpetuating pain. By needling into specific sites, such as hypersensitive skin or tight bands of muscle, this cycle is broken Trigger Point – Muscle spasm Chronic inflammation and pain results in muscle spasms and lead to changes in the muscle structure. Long lasting muscle spasm causes accumulation of fibrotic tissue inside the muscle (can be palpated as taut band) with subsequent muscle shortening. Trigger points - Location Taut bands of muscle and are especially tender to palpate. The muscle tendon junction and tendon attachment to bone provides a complete needling location for the tight muscle and mechanical distraction of fibrotic tissue, resulting in relaxation. The treatment will increases circulation to the area and decreases pressure on joints. Acupuncture for Pain Neuro-muscular mechanism Needling by blocking the excessive release of acetylcholine from the peripheral nerve terminal at the neuromuscular junction (where the nerve transmits signals to the muscle); or muscle-tendon conjunction, where golgi receptor located, inducing muscle contraction inhibition, resulting in muscle relaxation and pain releasing. Negative feedback regulation of muscle tension by Golgi tendon organs Golgi Tendon Organ “Golgi Points ?” ST36 GB34, 37, Sp6 LI3, 10 BL25 Si5 Acupuncture Back Pain- Piriformis Syndrome Role of natural anti-inflammatory Agents in Cancer Treatment WM Chemo or Radiation: limited effectiveness Side effects from cytotoxicity: immune, bone marrow, digestion, wellbeing EM Supportive therapy: immune, bone marrow, digestion, gut bacteria, detoxification (free radicals) Enhance and reduce resistance of chemo: anti-inflammation Cause of cancer treatment: inflammation/detox 11/10/10 Jing Liu, MD, PhD 108 Cancer and COX-2 A number of clinical investigations showed that high COX-2 activity was found in patients with a variety of cancers: Colorectal, gastric, breast, non-small cell lung, ovarian, hepatocellular, pancreatic, bladder, skin, and particularly, 80-90% colon cancer COX-2 Inhibitors for Chemo-resistance Chemotherapeutic drug resistance is an unresolved challenge in clinical cancer treatment, particularly for the metastasis carcinoma status. The inflammation and pro-inflammatory cytokines are strong intrinsic factors for promoting multiple drug resistance (MDR). Chemotherapy may induce the activities of COX-2 and inflammation. COX-2 stimulates the P-Glycoprotein of the MDR, which rejects the drug out of the cancer cells. COX-2 inhibitors, celecoxib, aspirin, ibuprofen, and indomethacin may enhance chemotherapy Synergistic Effect of Herbs with Chemo? Multiple target model of cancer cell for Natural COX-2 Inhibitors Multiple Signal Transduction systems (modulate the DNA/RNA and cell activities/growth, developed from evolution, primary cell to human being ) Growth factors Tyrosine Kinase EGFR/HER2 IGFR Pathway of Chemotherapy Resistance Breast Cancer Natural Anti-inflammatory Agents Enhance Effects of Chemotherapy Morphologic changes Fig 1. of MCF-7 cells treated with COPE and TAX Are Antioxidants counteract with Chemotherapy? Meith I. Block analyzed the results of antioxidants applications, including glutathione, melatonin, vitamin A, vitamin C, N-acetylcysteine, vitamin E, ellagic acid and antioxidant mixture, from randomized and controlled clinical trials in 845 articles. Conclusion: None of the trials reported evidence of significant decreases in efficacy from taking antioxidant supplements during chemotherapy. Are Antioxidants counteract with Chemotherapy? Instead, many of the studies suggested increased survival times, increased tumor responses, and less toxixity responses from taking antioxidants than controls[1] [1] Block KI, etc.Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic review of the evidence from randomized controlled trials. Int J Cancer. 2008 Are Antioxidants counteract with Chemotherapy? The natural supplements may be taken after the chemotherapeutic agents are eliminated from plasma, which could be from a few hours to a few days. The supplements should be stopped at least one day before the next chemotherapy session. The information about the pharmacological dynamics of the chemotherapeutic agents should be researched before the natural supplements is administered. Natural Medicine自然医学 Definition 1、基于自然界整体观发展的医学理论体系,强调人体的生理、疾病与自然界 的紧密联系。 2、强调人体内部整体间的相互关联。 3、承认个体之间的差异性,因而诊治体现个性化差异。 4、治疗手段,特别是药物,直接来源于自然界,强调其自然属性。 5、治疗、预防与调养相结合的、符合人体生理特征的治疗方针。 6、植根于悠久的民族、民间医学,具备丰富的临床实践经验。自然医学应融 合和吸收世界各国民族医学和自然疗法的精华,用现代医学的技术手段加以 证实和发展。 7. 中医药学应以其悠久的历史,博大系统的理论、丰富的实践以及可信的疗 效,在自然医学的形成和发展中占有重要地位。 11/10/10 Jing Liu, MD, PhD 118 End Inflammation and Endothelial Dysfunction to Microvascular Dysfunction Endothelial dysfunction is integral to the pathogenesis of many disorders: Atherosclerosis Autoimmune disorders Inflammation Infection Trauma Vascular Endothelial Mediators Nitric Oxide/L-Arginine-Herbs Nitric Oxide (NO) anti-inflammatory and anti-proliferative effects Endothelial function protection Atherosclerosis protection Nitric Oxide/L-Arginine-Herbs L-arginine Control blood pressure and improve heart function Reducing cholesterol and plaque formation Promote anti-aging growth hormone Enhancing immune function and stop some cancer cell growth Improving memory Improve erectile dysfunction Nitric Oxide/L-Arginine-Herbs Herb Dang Gui Bai Shao Bai Jili The signal molecule ·NO (nitric oxide) may initiate prostaglandin synthesis by reacting with superoxide anion (O2·-) to produce peroxynitrite, which oxidizes the heme iron enabling electron transfer from the active site tyrosine. Prostaglandin synthesis in response to some inflammatory stimuli is diminished by inhibitors of Nitric Oxide Synthase. Autoimmune disorders WM Prednisone, immune suppressor, T-cell inhibitor Adverse reaction: mal-metabolism cortisone withdrawal syndrome, immune dysfunction EM Immune enhancing and Immune suppression together: astraglus vs. scutellaria, Bupleurum Stimulating adrenal –cortisone function for cortisone withdrawal syndrome (NIH fund supported project) Gentle but effective T-cell or TNF inhibitor: Olivenol, Rapamycin, Dichroa febrifuga黄常山, Principle: TNF is a dual side blade sword 11/10/10 132 Infection WM Limitations of antibiotics in Chronic infection: immune function, beneficial bacteria damage, drug resistance Co-existing inflammation, congested microcirculation EM Detox - anti-pathogen De-congestion of circulation- open the microcirculation: antibiotic availability, flushing out toxins Promoting Qi – enhancing immune function Strengthen “spleen system” – protect digestion and prebiotic 11/10/10 Jing Liu 133 Natural therapy for autoimmune disorder David Fernandez (2010) discover: rapamycin can be an effective treatment in human lupus, SLE. regulates interferon-α and T cell and promote Th2 versus Th1 immune responses suggest that the colitis, including crohn’s disease and ulcerative colitis, can be well controlled by natural therapy in many cases, and can be well integrated with cortisone or immune suppressor Probiotic + Enzymes + Herbs + Diet Gastroesophageal reflux (GERD) WM H2 blocker – Zantac Proton pump inhibitor – Prilosec Mucosal protectors – sucralfate Motility drugs - empty stomach, Reglan. EM Mucosal protection: Gastric acid pseudo-overproduction, Deglycyrrhizinated licorice (DGL) Calming acid reflux and peptic ulcers by: Anti-inflammation and the pathogens Protect mucosal membrane by increasing the thick mucous production Free of the ingredients of increase fluid retention Anti-inflammation: Chamomile, slippery elm, coptis Motility promoting: Auklandia lappa 11/10/10 Digestive function promotion: Jing Codonopsis Liu, MD, PhD 135 穴位特异性 -安慰 针灸穴位特异性的质疑一直与针灸是否为安慰治疗的争论 并存。对穴位的特异性的解释经常困扰临床研究的设计和 结论。 穴位无特异性 = 安慰 穴位部分特异 = 部分安慰 穴位全部特异 = ? 安慰针对照原则 目的:排除术者与病人的“期望” 和暗示效应 要求:安慰刺激方式没有特定治疗作用 方法:a.针刺或其他刺激方式选在没有特定治疗作用的部 位,sham? b.受试者不能察觉安慰针与治疗针在外观和操作和 感觉上的差别 针刺部位选择的质疑 采用非传统中医穴位作为疗效安慰对照, 针刺穴位数目增加的历史。 “安慰穴位”可能是明日公 认的治疗穴位 采用近经络刺激点作为经络论证或疗效对照 不能排除经与络的连接。 只适用于证明经络的特异程度,不适于疗效判定。 安慰针刺部位选择原则 1,验证疗效: 应符合如下全部条件: a. 非经络非传统穴位。 b. 与治疗穴位保持一定距离,以回避“经与络”相关联的嫌疑 c. 二组穴位非处于同一神经节段分布 d. 二组穴位非同一解剖组织相关。例如,二穴不能位于同一肌肉上。 穴位的特异性与肌体组织结构相关。如肌肉、肌腱、骨膜,间质组织 。 安慰针刺部位选择原则 2,验证传统针灸经络理论 不同穴位或非穴位点:穴位特异性 离开经络的针点:经络特异性 安慰方式质疑 浅刺穴位点或非穴位点的方式作为安慰对照并不完全合理 . 假针具欺骗性的可靠性值得怀疑:a. 钝针头压迫到表皮, 不能排除“假针“的治疗作用; b. 反复使用;c. 有针灸体 验或知识者, 尤其是从签署同意书时获知是受试者 模拟皮表电刺激 :没有任何刺激的感觉所引起的心理反 应 症结 理想安慰方法:外观、感觉上与治疗组针灸没有区别,但 无特定疗效。即无暗示和期望效应。 为何目前的安慰对照设计很难完全达到标准?针灸未被纳 入西方主流医学的障碍之一。 问题的症结在于传统的安慰剂的概念和使用,不完全适用 于针灸? 药物:Placebo效应 对临床疗效具有重要影响:与疼痛相关的治疗中Placebo 作用可达50%。焦虑明显影响Placebo效应。 临床药物:单分子化学结构药物,有明确的特异受体或靶 点。其引起的生理或病理变化有明确的表现和体征。 如果表述出与药物作用或毒副作用无关的反应,特别是心 理、精神方面的反应,也可能被认为安慰效应。 针刺 -介入疗法? 针刺应与外科手术同属介入疗 法,在介入性治疗的临床研究 中不适于用安慰对照, 但这一 理由很难被西方医学界认同。 主要原因:手术的危险性和伤 害程度要远甚于针刺? 合理对照的选择(1) 2000年世界医学大会修订的《进行人体生物医学研究的伦 理道德原则》指明,测试一种新疗法时,应以当时最有效 的方法作对照,虽然并不排除使用安慰剂治疗对照,但仅 用于未有有效治疗方法对照时。 合理对照的选择(2) Placebo或Sham针刺的结果不应是作为结论的绝对依据。此外,没 有Placebo 但有相应对照的研究论文也不应再被一概视为“不科学 、不可靠“的依据。 重视针灸临床方法学整体与细节上与国际化标准的接轨。除了对照 的差别 组设计外,随机原则的使用,样本量的考虑,受试者同意书的措辞 以及严格的管理执行体系。 1. 德国2005年在一份临床针灸方法学的研究报告中回顾总结了1000 例 头痛,腰痛的治疗,结论是针灸完全可以按照严格的标准来完成临 床实验研究 合理对照设计的建议 最大限度的减少期望与暗示效应。为此,建立严格独立的随机分组, 诊断,治疗,资料收集,资料处理,统计处理系统。 按照病因,病理详细针灸适应症,例如高血压,头痛,腰痛的病例选 择或结果分析 用国际认可的标准量表,如疼痛,背功能量表 组成基础,临床,统计,管理专家体系的针灸临床研究队伍,特别是 加强对安慰效应的基础研究如fMRI 穴位特异性 Hypothesis 不同穴位刺激在大脑水平有相当的重叠反应,但强度不同 穴位刺激 在脊髓阶段的反应有相应的特异性,但在一定 刺激强度下有各脊髓阶段之间的重叠 穴位刺激, 特别是trigger 穴位的局部反应是相对特异的 针刺通过三级反应共同完成效应机制 针刺特异性: 大脑效应:多系统、多靶点 fMRI 研究的证据:针刺多个不同体表穴位后会在大脑神 经网络的躯体感觉区,边缘系统,扣带回前区,下丘脑, 海马回,大脑皮层前回,小脑蚓区 等不同神经元区域产 生广泛影响。 边缘系统,扣带回前区,大脑皮层前回,小脑蚓区等对精 神、情绪、心理状态有控制,调节作用。 针刺的反应过程有脑啡呔,单胺,多巴胺,5-羟色胺、等 神经介质的广泛参与。 针刺安慰效应 acupuncture placebo response 针刺的安慰效应(opioid placebo response) 主要集中在Posterior midcingulate cortex, pMCC 的尾部。 这一区域对躯体疼痛有最高密 度的反应。 吗啡的安慰效应(opioid placebo response) 主要集中在与内脏相关的 subgeneral anterior cingulated cortex 区域 fMRI 的研究显示,placebo 麻醉效应区,主要是在导水管周围灰质( PAG), 扣带回前区啄部(rostroil ACC), 岛区(insula), 杏仁核, 下丘脑, 与针刺的作用靶点有重叠 结果推测:Placebo效应可能是针刺的一个必然结果。 针灸适用于心身(Mind-Body)疾病治疗的机制之一。 假设:激发启动效应 burst – firing mechanism “得气”刺激信号激发了神经介质参与的神经网络通路信号系统的调 整。其中包括了支配精神、情绪的神经元的整合。 推论:与作用于神经、精神系统的化学药物仅作用于单一脑内受体不 同。针刺对大脑系统的作用是多方面的,不是单一的对某一受体的抑 制或增强,而是调整或重新整合式的,这一过程必然有控制情绪、精 神的神经元的被调整。 举例:针灸可以减轻焦虑、紧张的状态,而情绪的紧张程度与痛觉感 受的程度相关。 学说:针刺改变疼痛感受而不是疼痛本身 针刺安慰效应 Placebo效应,也就是说Placebo可以通过心理暗示获得, 也可能通过物理、化学刺激获得,仅是效应强度和治疗可 能带来的副作用可能是不同的. 针刺治疗的最常见适应症之一疼痛症与情绪状态有直接相 关。大脑前区在反应疼痛与情绪的过程中由扣带回区参与 了两者之间的整合. 情绪,精神心理的控制 3 针刺特异性的fMRI 证据 1 (A) Both manual (MA) and electro-acupuncture (EA) but not tactile control stimulation at ST-36 induce fMRI signal decrease in the amygdala as evidence by fMRI signal time-courses during stimulation blocks (gray). (B) The CTS patients demonstrated less hyperactivation and more focused SI finger representation to innocuous stimulation of the 3rd finger. (C) CTS patients demonstrated less separation of somatotopic representations. After acupuncture treatment, the 2nd and 3rd finger representations were more separated, approximating normal somatotopy in HC fMRI 证据: 穴位的特异性是相对的 尚没有确立针刺的特异反应区 针刺穴位与sham点似有不同的反应区 不同穴位, 不同刺激方法引起的信号有相当的重叠 针刺穴位较之钝针对边缘系统和边缘旁系统有更强烈的调整作用 Insula cortex 可能是针刺的特异反应区,而针刺在Dosolateral PFC, rostral ACC, 和 midbrain PAG 的反应可能与安慰期望程度有关 穴位特异性 Trigger point (扳机点) Trigger point 可以在传统穴位或非穴位位置上 潜伏期:无疼痛。在病理刺激下转化(寒冷、疲劳、损伤 、肌肉紧张) 被动期:可触摸到的疼痛 活动期:清楚感觉的疼痛,穴位面积增大。最早多出现在 神经干、体表浅层、肌门,数目随疼痛迁延增多 穴位特异性 穴位的局部反应 改善(微)循环 调节免疫功能、减少炎症 缓解肌紧张 调节神经(眩晕、哮喘、呕吐)