Published on March 30, 2008
Naturopathic Pain Management in Geriatric Populations: Naturopathic Pain Management in Geriatric Populations Rick Marinelli, N.D., M.Ac.O.M. Clinical Professor NCNM 1600 SW Cedar Hills Blvd. Portland, Oregon, 97225 www.natural-healthmedicine.com Naturopathic Principles : Naturopathic Principles First do no harm Find the cause Treat the whole person Prevention is the best cure Let nature do the healing Physician as teacher Unique Challenges in Geriatric Populations: Unique Challenges in Geriatric Populations Natural history of decline, self-care Prevention of incipient events Polypharmacy environment Depression, anxiety, social isolation more common and greatly contributes to pain First Intervention is Dietary and Individualized: First Intervention is Dietary and Individualized Emphasis is initially on reducing refined carbohydrates, optimizing protein, fatty acid and micronutrient intake Excess CHO intake has negative effect on insulin metabolism, weight gain, inflammation (perhaps 60%) Insufficient protein limits repair and regeneration (~30% < RDA) Excess n-6 PUFAs promote inflammation, cancer, poor circulation and contribute to decline Excess CHOs: Excess CHOs Decreased tolerance to carbohydrates with aging Epidemic of obesity, DM continuum, cardiovascular disease, hypertension Need less caloric intake with aging Generally better to markedly increase vegetables (increased micronutrient intake) and fruit intake than to rely on grains for carbohydrates Protein Optimization: Protein Optimization Protein synthesis is decreased with aging and therefore increased intake is usually necessary Protein-energy malnutrition is associated with impaired muscle function, decreased bone mass, immune dysfunction, anemia, reduced cognitive function, poor wound healing, delayed recovery from surgery, and ultimately increased morbidity and mortality Protein Optimization: Protein Optimization Common medical conditions such as gastrointestinal disease, malabsorption syndromes, acute and chronic infections, and hypermetabolism often cause anorexia, micronutrient deficiencies, and increased energy and protein requirements Elderly are major users of prescription medications, which can cause malabsorption of nutrients, gastrointestinal symptoms, and loss of appetite Micronutrients for OA: Micronutrients for OA A daily 12oz nutritional beverage containing milk-based micronutrients, vitamins, and minerals was beneficial in alleviating symptoms and dysfunction in subjects with osteoarthritis (n=31) Nutrition 2002 May;18(5):388-92 Low intake of micronutrients (vitamins C, E, and D, and beta-carotene) may adversely influence the progression of knee OA and the incidence of hip OA Curr Rheumatol Rep. 1999 Oct;1(1):48-53 Fatty Acid Modulation: Fatty Acid Modulation Reduction in the amount of fat intake enhanced several indices of immune response, including lymphocyte proliferation, natural-killer-cell activity, cytokine production, and delayed-type hypersensitivity Intake of omega-3 fatty acids reduced several aspects of neutrophil, monocyte, and lymphocyte functions, including the production of inflammatory mediators Nutrition 2001 Jul-Aug;17(7-8):669-73 Omega 6s as Agents of Inflammation and Decline: Omega 6s as Agents of Inflammation and Decline Omega-6 PUFAs , abundant in the Western diet, are precursors for a number of key mediators of inflammation including the 2-series of prostaglandins and IL-6 PGE2 , a cyclooxygenase (COX) metabolite of arachidonic acid, a omega-6 PUFA, is a potent mediator of inflammation and cell proliferation Omega 6s examples include safflower, corn, soybean, and cottonseed oils Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1751-6 Fatty Acid ModulationOmega 3s (n-3): Fatty Acid Modulation Omega 3s (n-3) The parent fatty acid in the omega 3 fatty acid family is alpha-linolenic acid (ALA) which is an essential fatty acid found in high concentrations in certain plant oils, such as flaxseed oil, walnut oil and canola oil Omega 3 fatty acids are formed from alpha-linolenic acid and these are mainly found in fish, fish oils and from other marine organisms Main marine omega 3 fatty acids are eicosapentaenoic acid (EPA), docosapentaenoic acid and docosahexaenoic acid (DHA) Fatty Acid ModulationOmega 3s (N-3): Fatty Acid Modulation Omega 3s (N-3) N-3 Fatty acids favorably affect atherosclerosis, coronary heart disease, inflammatory disease, and perhaps even behavioral disorders Docosahexaenoic acid (22:6n-3), which is a vital component of the phospholipids of cellular membranes, especially in the brain and retina, is necessary for their proper functioning Importance of n-3 fatty acids in health and disease, Connor WE Am J Clin Nutr 2000 Jan;71(1 Suppl):171S-5S Fish Oil as Solution: Fish Oil as Solution Increasing the omega-3 content of membrane phospholipid results in a decrease in mitogen-induced PGE(2) synthesis Data suggest that replacement of omega-6 PUFA with omega-3 PUFA in cell membranes can result in a decreased cellular response to mitogenic and inflammatory stimuli Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1751-6 Fish Oil as Healer: Fish Oil as Healer Reduction in strokes Decrease in arthritis pain Decrease in collagen and bone degrading enzymes Modulate inflammation in IBD, autoimmune disorders, dermatitis, asthma, Preliminary evidence of cancer prevention (lung, breast, colon) N-3 FA in Arthritis: N-3 FA in Arthritis N-3 fatty acids specifically modulate catabolic factors involved in articular cartilage degradation Dose related reduction in the expression and activity of proteoglycan degrading enzymes (aggrecanases) Reduced expression of inflammation-inducible cytokines (interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha) and cyclooxygenase (COX-2) but not the constitutively expressed cyclooxygenase COX-1 J Biol Chem 2000 Jan 14;275(2):721-4 Fish Oil in Arthritis: Fish Oil in Arthritis Omega 3s reduced, in a dose-dependent manner, the endogenous and IL-1-induced release of proteoglycan metabolites from articular cartilage explants and specifically abolished endogenous aggrecanase and collagenase proteolytic activity Expression of mRNA for ADAMTS-4, MMP-13, and MMP-3 (but not TIMP-1, -2, or -3) was also specifically abolished with n-3 PUFA supplementation Omega 3s abolished the expression of mRNA for mediators of inflammation (cyclooxygenase 2, 5-lipoxygenase, 5-lipoxygenase-activating protein, TNF- alpha, IL-1alpha, and IL-1beta) without affecting the expression for other proteins involved in normal tissue homeostasis Arthritis Rheum. 2002 Jun;46(6):1544-53. N-3 FA in (IBD): N-3 FA in (IBD) n-3 fatty acids inhibit leukotriene B4 formation as do the 5- aminosalicylates 2/5 studies showed a significant improvement in clinical activity and a steroid-sparing effect, respectively 1/5 showed beneficial effects of n-3 fatty acids in patients with Crohn's disease; however, there was clinical improvement, just falling short of significance, in patients with ulcerative colitis A large, 2 year trial of n-3 fatty acids in patients with ulcerative colitis off steroids, which was recently completed at the Universities of Munich and Mainz, showed a delay of the first episode of relapse, but no reduction in the cumulative relapse rate at 2 years Curr Opin Clin Nutr Metab Care 1999 Mar;2(2):117-20 Omega-3 in Cancer: Omega-3 in Cancer Modulation of omega-3/omega-6 polyunsaturated ratios with dietary fish oils in men with prostate cancer. Urology. 2001 Aug;58(2):283-8. Modulation of experimental colon tumorigenesis by types and amounts of dietary fatty acids. Cancer Res. 2001 Mar 1;61(5):1927-33. Three percent dietary fish oil concentrate increased efficacy of doxorubicin against mda-mb 231 breast cancer xenografts. Clin Cancer Res. 2001 Jul;7(7):2041-9. “Bad”Cytokines May Induce Anorexia, Sarcopenia, Apoptosis: “Bad”Cytokines May Induce Anorexia, Sarcopenia, Apoptosis “Bad” Cytokines contribute to lipolysis, muscle protein breakdown, nitrogen loss, and anorexia IL-6 levels become elevated and carry a poor prognosis Could function through direct catabolic effects, or by causing reduced dietary energy intake (the anorexia of aging), or by inducing insulin resistance or lowering growth hormone, IGF-1 concentrations Curr Opin Clin Nutr Metab Care. 2003 May;6(3):295-9 Omega 3s have been shown to downregulate “bad” cytokines as IL-6 as well as TNF, IL-1 and 2 in vivo and increase survival in animals Ann Nutr Metab. 1997;41(4):203-34. Fish Oil as Stroke Prevention in Women: Fish Oil as Stroke Prevention in Women A significantly reduced risk of thrombotic infarction was found among women who ate fish 2 or more times per week (multivariate RR, 0.49; 95% CI, 0.26-0.93) Women in the highest quintile of intake of long-chain omega-3 polyunsaturated fatty acids had reduced risk of total stroke and thrombotic infarction, with multivariate RRs of 0.72 (95% CI, 0.53-0.99) and 0.67 (95% CI, 0.42-1.07), respectively JAMA 2001 Jan 17;285(3):304-12. Fish Oil as Stroke Prevention in Men: Fish Oil as Stroke Prevention in Men Multivariate RR of ischemic stroke was significantly lower among those who ate fish 1 to 3 times per month (RR, 0.57; 95% confidence interval [CI], 0.35-0.95) However, a higher frequency of fish intake was not associated with further risk reduction; the RR was 0.54 (95% CI, 0.31-0.94) for men who consumed fish 5 or more times per week JAMA. 2002 Dec 25;288(24):3130-6 Omega-3 In Other Disorders: Omega-3 In Other Disorders The emerging role of omega-3 polyunsaturated fatty acids in the management of patients with IgA nephropathy. J Ren Nutr. 2001 Jul;11(3):122-8. Prevention of sudden death in CAD Am J Clin Nutr. 2003 Jul;78(1):65-71 Lower risk of death (especially arrhythmic IHD death) in ischemic heart disease Circulation 2003 Mar 18;107(10):1372-7 Decreases perimenopausal bone loss Prostaglandins Leukot Essent Fatty Acids. 2003 Jun;68(6):361-72. Exercise Improves Health, Vitality, Bodily Pain : Exercise Improves Health, Vitality, Bodily Pain General practitioners were prompted by the patient to give oral and written advice on physical activity during usual consultations For every 10 green prescriptions written, one person achieved and sustained 150 minutes of moderate or vigorous leisure activity per week, at 12 months Measures of self rated "general health," "role physical," "vitality," and "bodily pain" improved significantly Trend (but not significant) in lowering BP BMJ 2003 Apr 12;326(7393):793. Strength training in the elderly: effects on risk factors for age-related diseases: Strength training in the elderly: effects on risk factors for age-related diseases In addition to improved strength, function, endurance, muscle mass and power Reduces insulin resistance Decreases both total and intra-abdominal fat Increases resting metabolic rate in older men Prevents the loss of BMD with age Reduces risk factors for falls May reduce pain and improve function Sports Med. 2000 Oct;30(4):249-68 Herbal and Supplemental Approaches to Pain Management: Herbal and Supplemental Approaches to Pain Management Nutraceuticals Common examples are the GAGs ( GS, CS, HA) MSM, DLPA, Amino acids, fish oils, antioxidants, vitamins, minerals, and enzymes, probiotics Herbal extracts Vast pharmacopoeia from Western and Eastern traditions Common examples include Hypericum, Gingko, Corydalis, Ginger, Capsicum, Willow, Feverfew, Bromelain, Kava, Turmeric, Valerian, Licorice, Boswellia, Hawthorne Glucosamine as a Collagen Type II Enhancing, Pain Relieving Supplement: Glucosamine as a Collagen Type II Enhancing, Pain Relieving Supplement Glucosamine sulfate is a Biological Response Modifier of chondrocytes under conditions of joint stress Osteoarthritis Cartilage. 2003 May;11(5):335-42 Reduces knee OA symptoms and progression Lancet. 2001 Jan 27;357(9252):251-6. Decreases MMP-3 and aggrecanase expression Osteoarthritis Cartilage. 2003 Jun;11(6):424-32. Chondroitin Sulfate: Chondroitin Sulfate While GS is extracted from crab, shrimp, or lobster shell and is a smaller molecule and easily absorbed, CS is extracted from trachea cartilage, is a larger proteoglycan and is not a easily absorbed orally CS is probably more chondroprotective than chondroregenerative Topical applications may be better than oral CS May affect clotting time if used in those on ASA or heparin therapy NIH is presently evaluating with GS Proteolytic Enzymes in Inflammation: Proteolytic Enzymes in Inflammation Bromelain Plant Proteases Trypsin/Chymotrypsin Pancreatic enzymes Proteolytic Enzymes in Inflammation: Proteolytic Enzymes in Inflammation Clinical application of plant protease (Kimotab) in the surgical field. Nippon Geka Hokan. 1966 Mar 1;35(2):395-40 Clinical note on fluidifying activity on bronchial secretions by a plant proteolytic enzyme]. Gaza Int Med Chir. 1965 Sep 15;70(17):1455-67 Enzyme therapy of pulpo-apical affections. The lysozyme]. Rev Fr Odontostomatol. 1968 Aug-Sep;15(7):947-50 Bromelain : Ananas comusus: Bromelain : Ananas comusus Introduced in the U.S. 1957 ; was marketed as Ananase in the ’60s Therapeutic applications Aids digestion Anti-inflammatory Prevents edema Inhibition of platelet aggregation Enhanced wound healing Enhanced antibiotic absorption/antibiotic activity Bromelain : Ananas sppAnti-inflammatory Activity: Bromelain : Ananas spp Anti-inflammatory Activity Several mechanisms of action Activation of proteolysis at site of inflammation Fibrinolysis via plasminogen-plasmin system Depletion of kininogen Inhibition of inflammatory prostaglandins and induction of PGE1 Bromelain : Ananas spp: Bromelain : Ananas spp Studies in RA/OA with/without curcumin there was reduced need for corticosteroids Significant reduction in swelling, bruising, pain, healing time post-surgery Athletic injuries reduction of bruising , edema, healing time Bromelain : Ananas sppClinical Applications: Bromelain : Ananas spp Clinical Applications Thrombophlebitis - numerous studies DBPC of 73 patients with acute thrombophlebitis reduced all symptoms of inflammation including pain, edema, redness, elevated skin temperature at dose of 400-800 mg (high-strength, >1800 mcu) Seligman B: oral Bromelains as adjuncts in the treatment of acute thrombophlebitis. Angiology 20, 22-26, 1969 Bromelain : Ananas sppClinical Applications: Bromelain : Ananas spp Clinical Applications Musculoskeletal injuries(contusions, muscle strains/sprains, ligament tears) By decreasing fibrin, bromelain helps promote circulation and post-traumatic resorption of inflammatory by-products Masson M. Bromelain in the treatment of blunt injuries to the musculoskeletal system. A case observation study by an orthopedic surgeon in private practice. Fortschr Med 113(19):303-306. 1995 Oral Enzyme Equivalence With NSAIDs in Arthritis: Oral Enzyme Equivalence With NSAIDs in Arthritis In patients suffering from painful osteoarthritis of the knee, periarthritis of shoulder, and painful vertebral syndromes there was a statistical equivalence of the pain-scores, comparing diclofenac and enzymes. The study demonstrated equivalence of the treatment with NSAIDs compared to therapy with enzymes. Wien Med Wochenschr 1999;149(21-22):577-80 NSAIDs vs. Oral Enzymes in Rheumatic Disease: NSAIDs vs. Oral Enzymes in Rheumatic Disease Data of 3326 patients treated for rheumatic diseases between 1/93 and 3/95 were registered by 380 physicians Joint diseases, spinal diseases, rheumatic soft tissue diseases Treatment success (freedom from symptoms) with OE can be expected with a higher probability than with NSAID. OE were well tolerated showing much less adverse events when compared with conventional doses of NSAID. Arzneimittelforschung 2000 Aug;50(8):728-38 Oral Enzymes in Alzheimer’s Disease: Oral Enzymes in Alzheimer’s Disease Complexes with trypsin, alpha-chymotrypsin, and bromelain strongly degrade (125)I-Amyloid beta 1--42 These results suggest that up-regulation of Amyloid beta catabolism could probably reduce the risk of developing AD by preventing Amyloid beta accumulation in brain and vasculature Exp Neurol 2001 Feb;167(2):385-92 Oral Enzymes in Myocardial Infarction: Oral Enzymes in Myocardial Infarction Facilitates normalization of the atherogenic potential and has a positive action on the mediators of the inflammatory process. The effect of Wobenzym on the atherogenic potential and inflammatory factors at the rehabilitation stage for patients who have had a myocardial infarct Lik Sprava 2000 Jul-Aug;(5):111-4 Oral Enzymes in Chronic Lymphoma with Radiation and Chemotherapy: Oral Enzymes in Chronic Lymphoma with Radiation and Chemotherapy Systemic enzymes (wobenzime and wobe-mugos) as part of polychemotherapy to 24 patients with malignant lymphomas, who presented with large masses of lymphatic nodes had significant decreased in sclerosis Lik Sprava 1998 Aug;(6):141-3 Oral Enzymes in Chronic Prostatitis: Oral Enzymes in Chronic Prostatitis Uretrogenous prostatitis: 1) association with pancreatic pathology; 2) the presence of noninfectious agent; 3) autoimmune character Treatment includes Wobenzyme as part of a pathogenetic therapy with positive results Lik Sprava 1998 Aug;(6):118-20 Flavonoids: Flavonoids Are pigments in food and herbs Tea, apples, wine, fruits and vegetables, nuts are primary dietary sources Inverse relationship of dietary flavonoids and cardiovascular disease, stroke, and cancer in multiple analyses from Zutphen Elderly Study Common flavonoids are polyphenols such as resveratrol, catechins, quercitin, naringen, pro/anthocyanidins Generally have antioxidant, circulation enhancing, collagen stabilizing effect Flavonoids: Flavonoids Middleton et al. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000 Dec;52(4):673-751 Morino et al. Specific regulation of Heat Shock Proteins in human tumor cell lines by flavonoids. In Vivo 1997 May-Jun;11(3):265-70, Green Tea Polyphenols, Inflammation and Skin Cancer: Green Tea Polyphenols, Inflammation and Skin Cancer (EGCG) epigallocatechin-3-gallate has been shown to modulate the biochemical pathways involved in inflammatory responses, cell proliferation and responses of chemical tumor promoters as well as ultraviolet (UV) light-induced inflammatory markers of skin inflammation Int J Oncol 2001 Jun;18(6):1307-13 Green Tea Polyphenols in Periodontal Disease and Inflammation: Green Tea Polyphenols in Periodontal Disease and Inflammation In an RCT of 47 people green tea candy extract was shown to have a significant effect on the API (approximal plaque index) and the SBI (sulcus bleeding index) after seven and 21 days (8 candies a day) Eur J Med Res 2000 Nov 30;5(11):463-7 Inhibiting Soft-tissue Inflammation and Collagen Degradation(GTP): Inhibiting Soft-tissue Inflammation and Collagen Degradation(GTP) Green tea polyphenols(GTP) inhibit MMP-2, MMP-9 and MMP-12 in vitro (elastin,gelatin) and in vivo1 (human glioblastoma,pituitary tumors) Most potent of these were the catechins ECG and EGCG but included resveratrol, genistein, and organosulfur compounds from garlic 1Biochim Biophys Acta 2000 Mar 16;1478(1):51-60 Flavonoid Antioxidants and Sterols in Vegan Diet and Rheumatic disease: Flavonoid Antioxidants and Sterols in Vegan Diet and Rheumatic disease Uncooked vegan diet and consisting of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health in RA and FM pts. Toxicology 2000 Nov 30;155(1-3):45-53 Ajoene, a natural product with non-steroidal anti-inflammatory drug (NSAID)-like properties? Biochem Pharmacol 2001 Mar 1;61(5):587-93 Addressing Soft-tissue Inflammation and Collagen DegradationSerine Protease and MMP Inhibitors: Addressing Soft-tissue Inflammation and Collagen Degradation Serine Protease and MMP Inhibitors OPCs/ Bioflavonoids/Antioxidants in general Catechins (green tea polyphenols) Boswellia Scutellaria, Triptyrigium, Angelica spp,Evodia GS,CS (Glycosaminoglycans,GAGs) Omega 3 oils NAC/MSM/Allicins (organosulfur compounds) Tetracyclines (Streptomyces spp) Statins (Aspergillis spp, Monascus purpureus) Antioxidants as Adjuvants in Rheumatic disease: Antioxidants as Adjuvants in Rheumatic disease Group I: Intramuscular methotrexate (CAS 59-05-2; 12.5 mg/week), oral sulphasalazine (CAS 599-79-1; 0.5 g b.i.d.) and indometacin (CAS 53-86-1; 100 mg suppository at bed-time). Group II: the patients received the standard treatment plus a combination of antioxidants. Group III:received a high dose of vitamin E (400 mg t.i.d.) in addition to the standard treatment. With adjuvant therapy of either the antioxidant combination or a high dose of vitamin E the symptoms of arthritis were better controlled from the first month (n=30) Arzneimittelforschung 2001;51(4):293-8 Antioxidants As Adjuvants in Alzheimer’s Disease: Antioxidants As Adjuvants in Alzheimer’s Disease The products of inflammatory reactions such as prostaglandins (PGs; PGE1 and PGA1), free radicals, cytokines, and complement proteins are neurotoxic NSAIDs inhibit the synthesis of PGs, reduce the rate of deterioration of cognitive functions in patients with advanced AD Cholinergic drugs are routinely used in the treatment of AD to improve cognitive functions Therefore a combination of all are more likely to be effective Clin Neuropharmacol 2000 Jan-Feb;23(1):2-13 Modulation of Oxidation in Prevention/Treatment of PD: Modulation of Oxidation in Prevention/Treatment of PD Evidence suggests PD involves multifactorial, oxidative neurodegeneration, and that levodopa therapy adds to the oxidative burden Substantia nigra is vulnerable to oxidative damage, having high content of oxidizable dopamine, neuromelanin, polyunsaturated fatty acids, and iron, and relatively low antioxidant complement with high metabolic rate Integrative management of PD requires: (1) dietary revision, especially to lower calories; (2) rebalancing of essential fatty acid intake away from pro-inflammatory and toward anti-inflammatory prostaglandins; (3) aggressive repletion of glutathione and other nutrient antioxidants and cofactors; (4) energy nutrients acetyl L-carnitine, coenzyme Q10, NADH, and the membrane phospholipid phosphatidylserine (PS), (5) chelation as necessary for heavy metals; and (6) liver P450 detoxification support Altern Med Rev 2000 Dec;5(6):502-29 Glutathione in Inflammation, Cancer : Glutathione in Inflammation, Cancer Glutathione in its reduced form (GSH) is the most powerful intracellular antioxidant, GSH concentration can be influenced by exogenous administration of GSH (as intravenous infusion or as aerosol) GSH may be useful adjuvant therapy in intoxication, diabetes, uremia, sepsis, inflammatory lung processes, coronary disease, cancer and immunodeficiency states Wien Klin Wochenschr 2000 Jul 28;112(14):610-6 Antioxidants in Pancreatitis: Antioxidants in Pancreatitis Treatment with a complex containing L-methionine, beta-carotene, vitamin C, vitamin E and organic selenium Of 10 patients with chronic pancreatitis who completed treatment, the intensity of pain was reduced considerably in 9 (61.5 +/- 21.5 mm vs. 19.6 +/- 26.1 mm, p = 0.03), and pain was completely absent in 3 of these patients Rev Esp Enferm Dig 2000 Jun;92(6):375-85 Inflammation in Type II Diabetes, PCOS: Inflammation in Type II Diabetes, PCOS Elevated levels of CRP and IL-6 predict the development of type 2 DM. These data support a possible role for inflammation in diabetogenesis. JAMA 2001 Jul 18;286(3):327-34 “Women with PCOS have significantly increased CRP concentrations relative to women with normal menstrual rhythm and normal androgen levels. We propose low grade chronic inflammation as a novel mechanism contributing to increased risk of CHD and type 2 diabetes in these women J Clin Endocrinol Metab 2001 Jun;86(6):2453-5 Inflammation in Diabetes: Inflammation in Diabetes Flavonoids diosmin (90%) and hesperidin (10%), in a group of 28 Type 1 diabetic patients in a double blind placebo-controlled study. Parameters of glycation and oxidative stress were measured before and after the intervention Decrease in glycation and HgbA1c unrelated to glycemic control was noted, with increased glutathione peroxidase activity Diabetes Nutr Metab 1999 Aug;12(4):256-63 Vit C in Inflammatory Atherosclerosis: Vit C in Inflammatory Atherosclerosis Peripheral arterial disease (PAD) is a severe atherosclerotic condition frequently accompanied by inflammation and oxidative stress Subclinical vitamin C deficiency (<11.4 micromol/L), confirmed by low serum alkaline phosphatase activity, was found in 14% of the PAD patients Vitamin C concentrations are lower in intermittent claudication patients, is associated with higher CRP levels and severity of PAD Circulation 2001 Apr 10;103(14):1863-8 Low DHEAS in Inflammatory Disorders: Low DHEAS in Inflammatory Disorders Mean DHEAS level was markedly lower in the pemphigus (as with systemic lupus erythematosus, rheumatoid arthritis, polymyalgia rheumatica, giant cell arteritis) (n=46) DHEAS levels were independent of steroid treatment Clin Exp Rheumatol 1995 May-Jun;13(3):345-8 Low DHEAS in Inflammatory Arthritis/Synovitis: Low DHEAS in Inflammatory Arthritis/Synovitis Serum DHEAS and its relation to clinical variables in RA, spondyloarthropathy, and inflammatory arthritis in 87 pts was performed “Low DHEAS concentrations are commonly encountered in inflammatory arthritis, especially in women” Arthritis Res 2001;3(3):183-8 Physical Medicine Modalities: Physical Medicine Modalities Traditional hydrotherapy Manual therapy Electrotherapy Ultra/Infra-Sound Needling therapies Acupuncture Myofascial trigger point injections Neural therapy Prolotherapy (RIT) Ligaments and Tendons at the Fibro-Osseous Junction: Ligaments and Tendons at the Fibro-Osseous Junction Hackett postulated in 1939 that the major cause of back pain was tendon and ligament relaxation In his initial animal experiments he demonstrated a 30-40% increase in tendon size after injection with Sylnasol, later with zinc sulfate, and silica oxide Introduced the term prolotherapy in 1956, emphasized the postulates of Steindler, developed maps of pain referral patterns Newer Studies In Prolotherapy: Newer Studies In Prolotherapy Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity CONCLUSION: Prolotherapy injection with 10% dextrose resulted in clinically and statistically significant improvements in knee osteoarthritis. Preliminary blinded radiographic readings (1-year films, with 3-year total follow-up period planned) demonstrated improvement in several measures of osteoarthritis severity. ACL laxity, when present in these osteoarthritic patients, improved. N=110 Altern Ther Health Med 2000 Mar;6(2):68-74, 77-80 Newer Studies In Prolotherapy: Newer Studies In Prolotherapy “Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity” At the 3 year follow-up, pain at rest, pain with walking, and pain with stair use had improved by 45%, 43%, and 35% respectively CONCLUSION: In patients with symptomatic anterior cruciate ligament laxity, intermittent dextrose injection resulted in clinically and statistically significant improvement in ACL laxity, pain, swelling, and knee range of motion Altern Ther Health Med. 2003 May-Jun;9(3):58-62 Newer Studies In Prolotherapy: Newer Studies In Prolotherapy Randomized, prospective, placebo-controlled double-blind study of dextrose prolotherapy for joints: evidence of clinical efficacy CONCLUSION: Dextrose prolotherapy was clinically effective and safe in the treatment of pain with joint movement and range limitation in osteoarthritic finger joints. N=150 joints in 27 patients J Altern Complement Med 2000 Aug;6(4):311-20 Categories of Herbs for Pain Control: Categories of Herbs for Pain Control Analgesics Anti-convulsants Anti-depressants Anti-inflammatories Anxiolytics Narcotics Sedatives Alteratives/Adaptogen Materia Medica: Materia Medica Bromelain Cayenne Feverfew Ginger Gingko Boswellia Corydalis Guggulipid Kava St. John’s wort Turmeric Valerian Griffonia (5-HTP) Hawthorne Licorice Grape Seed Extract Ginger : Zingiber officianalis Therapeutic Applications : Ginger : Zingiber officianalis Therapeutic Applications N/V Motion sickness Arthritis Analgesic Migraine HA Cardiotonic Ginger : Zingiber officianalisPharmacology: Ginger : Zingiber officianalis Pharmacology Analgesic, antioxidant Inhibition of inflammatory prostaglandins, thromboxane and leukotriene synthesis Inhibition of platelet aggregation Cholesterol-lowering, choleretic effect Cardiotonic, GI protective actions, thermogenic properties, antibiotic activity Kiuchi F et al.: Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylhepatanoid. Chem Pharm bull 40, 387-391, 1992 Neuropharmacology 31, 1165-1169, 1992 Ginger : Zingiber officianalisAnti-inflammatory : Ginger : Zingiber officianalis Anti-inflammatory Several studies have shown efficacy in RA and OA, muscle discomfort Recommended dosage 500-1,000mg a day. Many patients took 3-4x this dose with quicker and better relief Srivastava et al.: Ginger in rheumatic disorders. Med Hypothesis 29, 25-28, 1989 Srivastava et al.: Ginger in rheumatism and musculoskeletal disorders. Med Hypothesis 39,342-348, 1992 Ginger : Zingiber officianalisKnee Osteoarthritis: Ginger : Zingiber officianalis Knee Osteoarthritis Statistically significant effect on reducing symptoms of OA of the knee RCT (n=247), multicenter trial, parallel, 6 wk trial Less knee pain with standing, after walking Reduction in the Western Ontario and McMaster Universities osteoarthritis composite index Good safety profile, with mostly mild GI adverse events in the ginger extract group. Arthritis Rheum. 2001 Nov;44(11):2531-8 Ginger : Zingiber officianalisAnalgesic: Ginger : Zingiber officianalis Analgesic Analgesic effects in animals is thought to be the result of shagaol inhibiting the release of Substance P Onogi T, et al.: Capsaicin-like effect of (6) shogoal on substance P-containing primary afferents rats; A possible mechanism of its analgesic action. Neuropharmacology 31, 1165-1169, 1992 Ginger : Zingiber officianalisAntioxidant: Ginger : Zingiber officianalis Antioxidant Potent inhibitor of oxidation of LDL, lowers cholesterol, attenuates atherosclerotic change1 Potent antioxidant in lipid peroxidation generally, including linoleic acid2 1Furhman et al. Ginger extract consumption reduces plasma cholesterol, inhibits LDL oxidation and attenuates development of atherosclerosis in atherosclerotic, apolipoprotein E-deficient mice. J Nutr 2000 May;130(5):1124-31 2Shobana S, Naidu KA, Antioxidant activity of selected Indian spices. Prostaglandins Leukot Essent Fatty Acids 2000 Feb;62(2):107-10 . Ginger : Zingiber officianalisCardiotonic: Ginger : Zingiber officianalis Cardiotonic Gingerol has shown potent cardiotonic activity in animal models (positive inotropic and chronotropic action) Shoji N, et al.: Cardiotonic principles of ginger (Z. officianalis). J Pharm Sci 10, 1174-1175, 1982 Kobayashi M, et al.: Cardiotonic action of (8) gingerol, an activator of the Ca++-pumping ATPase of sarcoplasmic reticulum of guinea pig arterial muscle. J Pharmacol Exp Ther 246, 667-673, 1988. Gingko: Gingko bilobaTraditional/modern Use: Gingko: Gingko biloba Traditional/modern Use Chinese used fruits/seeds since 2800 B.C. to “benefit the brain”, relieve symptoms of cough and asthma, to eliminate filaria Now used primarily as GBE in Europe for circulatory system disorders, cerebrovascular insufficiency,as an anti-asthmatic, and as a nootropic (mild-moderate dementia) 1988 in Germany there were more Rxs for GBE than any other drug(5.4M) Gingko: Gingko bilobaPharmacology: Gingko: Gingko biloba Pharmacology Membrane-stabilizing effect by activating Na+ pump Effects on vascular endothelium by stimulating EDRF and prostacyclin Effects are greatest in areas of poor perfusion Fungfeld EW (ed.):Rokan (Gingko biloba). Recent Results in Pharmacology and Clinic. Springer-Verlag, NY, 1988 DeFeudis FV(ed.): Gingko biloba Extract (Egb 761); Pharmacological Activities and Clinical Applications. Elsevier, Paris, 1991 Gingko biloba Clinical Applications: Gingko biloba Clinical Applications Chronic cerebrovascular insufficiency Peripheral vascular insufficiency Age-related memory/cognitive impairment. Mild-moderate dementia of Alzheimer’s type Vertigo /tinnitus, cochlear deafness Retinopathy/macular degeneration Neuralgia/neuropathy Depression Gingko ~ Effects on Vertigo: Gingko ~ Effects on Vertigo Haguenauer (1986) RCT study of 70 pts. with vertigo<2yrs. Treatment group had 74.7%(VAS) improvement vs. 18.6% for placebo group. Gingko Biloba.Press Med 15, 1569-1572, 1986 Claussen(1986) RCT study in 50 aged pts.with vertigo using craniocorpography studies showed significant reduction in oscillation amplitude Gingko ~ CNS activity: Gingko ~ CNS activity Neuroprotective effect in ischemia and traumatic brain injury1 Enhanced neurotrophic and neuritogenic effect post-injury2 1Advances in Gingko biloba Extract Research on the CNS, Elsevier, 1992 2Advances in Gingko biloba Extract Research on Neuronal Plasticity, Elsevier, 1996 Gingko biloba Retinal Effects: Gingko biloba Retinal Effects Improvement in long-distance visual acuity in macular degeneration and DM retinopathy Protective effects against free-radical damage to retina Shown to prevent DM retinopathy in diabetic rats DeFeudis FV(ed.): Gingko biloba Extract (Egb 761); Pharmacological Activities and Clinical Applications. Elsevier, Paris, 1991 Lanthony et al, Gingko biloba. J Fr Ophtalmol 11, 671-674, 1988 Gingko in Ischemic Heart Disease, Cerebral Infarction, Chronic Inflammation, and Aging.: Gingko in Ischemic Heart Disease, Cerebral Infarction, Chronic Inflammation, and Aging. GBLE has an antioxidant action as a free radical scavenger GBLE exerts an anti-inflammatory effect on inflammatory cells by suppressing the production of active oxygen and nitrogen species Beneficial effects on neuron degenerative diseases by preventing chronic oxidative damage Antioxid Redox signal 1999 winter;1(4):469-80 Gingko biloba Effects on Peripheral Vasculature: Gingko biloba Effects on Peripheral Vasculature Marked improvement in intermittent claudication DM PVD, Raynaud’s, acrocyanosis, postphlebitis syndrome Shown to be superior to exercise, pentoxifylline (Trental) in pain-free walking distance, plethysmographic/doppler US findings, blood lactate levels Angiology 45, 339-345, 1994 RCT (n=111) of EGb 761 (40mg tid) in peripheral occlusive arterial disease patients with Fontaine stage II b is very safe and causes a significant and therapeutically relevant prolongation of the patients' walking distance Vasa 1998 May;27(2):106-10 Gingko bilobaNerve cell effects: Gingko biloba Nerve cell effects Membrane-stabilizing and free-radical scavenging are most evident in brain and nerve cells GBE promotes in nerve transmission rate, synthesis and turn-over of brain NTs, normalizes ACh receptors in the hippocampus Normalizes circulation in areas most affected by microembolization (hippocampus and striatum) Fungfeld EW (ed.):Rokan (Gingko biloba). Recent Results in Pharmacology and Clinic. Springer-Verlag, NY, 1988 Gingko bilobaNerve cell effects: Gingko biloba Nerve cell effects Exerts protective effect on neurodegenerative, sensory, and vascular diseases EGb 761-induced inhibition of glucocorticoid production is due to specific transcriptional suppression of the adrenal PBR (peripheral-type benzodiazepine receptor) gene Seven genes were identified whose expression was strongly modified by the EGb 761 treatment and likely linked to neuroprotective action including genes involved in antioxidant defenses and in stress response Cell Mol Biol (Noisy-le-grand). 2002 Sep;48(6):641-6 Cell Mol Biol (Noisy-le-grand). 2002 Sep;48(6):633-9. Cell Mol Biol (Noisy-le-grand). 2002 Sep;48(6):601-11. Gingko bilobaMemory Effects: Gingko biloba Memory Effects In DBPC study of post menopausal women taking 120mg of gingko qd: Significantly better than the placebo group in a matching-to-sample test of nonverbal memory Test of frontal lobe function (rule shifting) and in the Paced Auditory Serial Addition Test (PASAT) (which measures sustained attention but also involves frontal lobe function), the group treated with Ginkgo performed significantly better than the placebo group Pharmacol Biochem Behav. 2003 Jun;75(3):711-20 Gingko bilobaMemory Effects: Gingko biloba Memory Effects Trial results do not support the view that Ginkgo is beneficial for patients with dementia or age-associated memory impairment J Clin Epidemiol. 2003 Apr;56(4):367-76 These results suggest that C4A(Egb761) treatment may reduce the risk of developing Alzheimer's dementia in elderly women (n=1462 women, age > 75) J Gerontol A Biol Sci Med Sci. 2003 Apr;58(4):372-7 Overall, the results from both objective, standardized, neuropsychological tests and a subjective, follow-up self-report questionnaire provided complementary evidence of the potential efficacy of Ginkgo biloba EGb 761 in enhancing certain neuropsychological/memory processes of cognitively intact older adults, 60 years of age and over Hum Psychopharmacol. 2002 Aug;17(6):267-77 Gingko bilobaMemory Effects: Gingko biloba Memory Effects 6-week study, RCT N=203, age >60, normal cognitive function (mini mental state exam, score >26), dose 40mg tid Indicate that ginkgo did not facilitate performance on standard neuropsychological tests of learning, memory, attention, and concentration or naming and verbal fluency in elderly adults without cognitive impairment when taken as manufacturers suggest JAMA 2002 Aug 21;288(7):835-40 Gingko bilobaDosage/side-effects: Gingko biloba Dosage/side-effects 80 mg capsules of SE, dose from 80mg to 240mg in divided doses In 9,772 taking GBE (leaf-extract) side-effects uncommon ; 21 cases of GI discomfort, 7 cases of HA, 6 cases of dizziness Contact with fruit-pulp can cause Rhus-like reaction Exercise caution if patient is on anti-coagulant or ASA therapy EGb 761 is a standardized extract(SE) of dried leaves of Ginkgo biloba containing 24% ginkgo-flavonol glycosides, 6% terpene lactones such as ginkgolides A, B, C, J and bilobalide St. John’s Wort : Hypericum perforatum Therapeutic Actions: St. John’s Wort : Hypericum perforatum Therapeutic Actions Anti-depressant/SAD Anti-viral Antioxidant Sleep disorders Topical as wound-healing agent St. John’s Wort : Hypericum perforatumPharmacology: St. John’s Wort : Hypericum perforatum Pharmacology Hypericin and psuedohypericin exhibit strong anti-viral activity against HSV1,2, influenza A/B, EBV, vesicular stomatitis virus Meruelo et al. Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: Aromatic polycyclic diones hypericin and psuedohypericin.Proc Natl Acad Sci USA 1988; 85:5230-5234 St. John’s Wort : Hypericum perforatumPharmacology: St. John’s Wort : Hypericum perforatum Pharmacology Constituent hyperforin has significant serotonergic activity and inhibits synaptosomal uptake of dopamine, norepinephrine, GABA and L-glutamate Chatterjee et al. Hyperforin as a possible antidepressant component of hypericum extracts. Life Sci 1998 63:6 499-510 St. John’s Wort : Hypericum perforatumAntidepressant: St. John’s Wort : Hypericum perforatum Antidepressant Official German Comm E Monograph lists psychovegetative disturbances, depressive states, fear, nervous disturbance as indications for use Many studies have shown as effective as standard anti-depressants but better tolerated with fewer side-effects St. John’s Wort : Hypericum perforatumAntidepressant: St. John’s Wort : Hypericum perforatum Antidepressant In multiple studies hypericum has been shown to be equipotent to SSRIs in relieving depression with greater safety profile and better tolerance European Neuropsychopharmacology 1999, 9: 461-468 Clinical therapy 2000, 22: 411-419 International clinical psychopharmacology 2000, 15: 61-68 Compr psychiatry 2000, 41: 133-137 St. John’s Wort : Hypericum perforatumAntidepressant: St. John’s Wort : Hypericum perforatum Antidepressant In severe depression Hypericum(LI 160) @600mg tid vs. imipramine 50mg tid Both drugs gave similar reductions in HAMD, CGI and D-S and considered effective while Hypericum had less side-effects Vorbach EU, et al. Pharmacopsychiatry 1997;30(Suppl):81-5 St. John’s Wort : Hypericum perforatumDosage: St. John’s Wort : Hypericum perforatum Dosage Anti-depressant dosage of standardized extract (0.3% hypericin) is 300mg tid cc for mild-moderate depression Anti-viral optimal dosage unknown but studies in HIV have shown encouraging results with 1mg hypericin qd As topical usually in combination with Arnica, Bellis, Eupatorium, Belladonna St. John’s Wort : Hypericum perforatumPotential Adverse Effects: St. John’s Wort : Hypericum perforatum Potential Adverse Effects Induction of Cytochrome P450 (CYP 3A4 mono-oxygenase) resulting in serum reduction of theophylline, digoxin, cyclosporine, coumarin, OCPs, indinavir and xenobiotics National Academy of Science USA 2000, 97,7500-7502 Lancet 2000, 355, 134-138 St. John’s Wort : Hypericum perforatumAdverse Effects: St. John’s Wort : Hypericum perforatum Adverse Effects Can cause severe photosensitivity in animals (hypericism) Reports of photosensitivity in humans is rare up to 11.25mg of total hypericin (tanning improved) The usual cautions with MAO inhibitors apply (avoid tyramine foods, l-dopa, 5-HTP, Tyr) May cause mild gastric upset in sensitive individuals Turmeric: Curcuma longa: Turmeric: Curcuma longa Ancient Ayurvedic herb mentioned >5000 yr. Ago ‘Olena in Hawaiian medicine Traditionally used as food preservative to enhance palatability, prevent oxidation/rancidity of fats/oils 8X more potent than Vit E in preventing lipid peroxidation Turmeric : Curcuma longa Therapeutic Actions : Turmeric : Curcuma longa Therapeutic Actions Antioxidant Anti-inflammatory Anti-cancer Hepatoprotective and choleretic Turmeric : Curcuma longa Pharmacology: Turmeric : Curcuma longa Pharmacology depletes nerve endings of substance P inhibits leukotriene formation and platelet aggregation promotes fibrinolysis inhibition of neutrophil inflammatory response stabilization of cell membranes Turmeric : Curcuma longa Pharmacology : Turmeric : Curcuma longa Pharmacology Active constituent curcumin and volatile oil fraction Increases glutathione S-transferase Antioxidant against intrinsic oxidants as superoxide, H2O2, hydroxyl radicals , lipid peroxides In acute inflammation comparable to phenylbutazone or cortisone but without toxicity Int J Clin Pharmacol Ther Toxicol. 1986 Dec;24(12):651-4. Turmeric: Curcuma longaPharmacology: Turmeric: Curcuma longa Pharmacology Anti-cancer effects by inhibiting formation of mutagenic pyrrolysates. 40% reduction of benzopyrenes in smokers’ urine inhibits formation of aflatoxin and aflatoxin-induced liver damage in vitro inhibition of nitric oxide derivatives by 50% Decreased toxic effect/increased therapeutic effect of anticancer drugs Turmeric : Curcuma longaAbdominal Pain: Turmeric : Curcuma longa Abdominal Pain In combination with chelidonium [Schollkraut/curcuma (Cholagogum F Nattermann) ] demonstrated significant decrease in RUQ pain due to biliary dyskinesia in a RCT Niederau, Gopfert.The effect of chelidonium and turmeric root extract on upper abdominal pain due to functional disorders of the biliary system. Results from a placebo-controlled double-blind study. Med Klin 1999 Aug 15;94(8):425-30 Turmeric : Curcuma longa Dosage: Turmeric : Curcuma longa Dosage Anti-inflammatory 400-600mg TID of curcumin Whole herb turmeric need 8g+ tid In combination with bromelain probably best 20’ AC because of poor absorption (40-85% unchanged thru gut) Turmeric : Curcuma longa Toxicity : Turmeric : Curcuma longa Toxicity None reported at standard doses LD 50 of curcumin, turmeric and it’s alcoholic extracts not determined because in rats up to 2.5g/kg no mortality or genetic damage was noted High doses is ulcerogenic in rats (curcumin 100mg/kg) Valerian: Valeriana officianalis: Valerian: Valeriana officianalis Dioscorides et al described as Phu Traditionally used for muscle spasms, emotional tension, insomnia, hysteria, fatigue, menstrual cramps >120 chemical components from root/essential oil Valerian : Valeriana officianalis Therapeutic uses: Valerian : Valeriana officianalis Therapeutic uses Sedative Anxiolytic Spasmolytic Anti-stress Valerian : Valeriana officianalis Pharmacology: Valerian : Valeriana officianalis Pharmacology Active constituents valeric a. isovaleric a. (sesquiterpenes), valepotriates, hydroxypinoresinol which vary according to source Normalizes CNS (sedative in agitation, stimulant in extreme fatigue) Binds BZ receptors and enhances GABA Smooth muscle relaxant, choleretic, anti-tumor and antibiotic activity J Pharm Pharmacol 1999 May;51(5):505-12 Valerian : Valeriana officianalis Clinical applications: Valerian : Valeriana officianalis Clinical applications Primarily as sedative in the treatment of insomnia Improves sleep quality, deeper stage 3 and 4 with less morning sleepiness Mild muscle relaxant activity due to CNS depression Aid in benzodiazepine, barbituate withdrawal Valerian : Valeriana officianalis Clinical applications: Valerian : Valeriana officianalis Clinical applications Several RCT have demonstrated improvement in slow wave sleep latency1,2, increased REM vs. NREM1,2, equivalency with oxazepam 2 in sleep induction with markedly fewer adverse effects 1Pharmacopsychiatry 2000 Mar;33(2):47-53 2Forsch Komplementarmed Klass Naturheilkd 2000 Apr;7(2):79-84 Valerian : Valeriana officianalis Dosage: Valerian : Valeriana officianalis Dosage Dried root (or as tea): 1-2g Tincture (10-20%) : 1-1.5 tsp (4-6ml) Fluid extract (1:1) : 0.5-1 tsp (1-2ml) Valerian extract (0.8% valeric acid) :150-300mg The above 30-45’ h.s. or up to qid Valerian : Valeriana officianalis Toxicity : Valerian : Valeriana officianalis Toxicity GRAS approved for food use by FDA Safety of valepotriates questioned, best to use water-soluble extracts standardized for valeric acid content Griffonia simplicifolia ~ 5-HTP : Griffonia simplicifolia ~ 5-HTP 5-HTP readily crosses blood-brain barrier Approximately 70% absorption Increases serotonin in the CNS Also increases melatonin, dopamine, norepinephrine, and beta endorphin in the CNS Van Praag et al. Nutrition and the brain. NewYork. Raven press;1986:89-139 Limiting Factors for L-Try entering CNS: Limiting Factors for L-Try entering CNS Stress, elevated cortisol, hi dose L-Tryptophan Increased kynurenine inhibits transport of LT into CNS LT competes with Tyr, Phe, Val, Leu, Isoleucine for transport to CNS LT may go to protein synthesis, niacin LT-Serotonin rate limited by Try hydoxylase which is inhibited by insulin resistance, stress, B6/Mg def Clinical Studies ~ Depression: Clinical Studies ~ Depression 5-HTP vs. Conventional Anti-Depressants Compared with fluvoxamine 150mg tid and 5-HTP 100mg tid had similar effects (5-HTP considered superior but not statistically) 5- HTP was better tolerated Poldinger et al. Psychopathology 1991;24:53-81 Clinical Studies ~ Depression: Clinical Studies ~ Depression 5-HTP vs. Conventional Anti-Depressants In severe depression vs. chlorimipramine/imipramine, 5-HTP shown to be as effective with doses up to 1200mg qd fewer side effects were noted Angst J et al. Arch Psychiatr Nervenkr 1977;224:175-186 Migraine Headaches ~ 5-HTP: Migraine Headaches ~ 5-HTP 124 subjects with 5-HTP 600mg qd vs. methysergide for 6 mos 75% had prevented or substantially decreased # of migraines not considered statistically significant Titus et al. Eur Neurol 1986;25:327-329 Fibromyalgia: Fibromyalgia Three trials report improvement with 5-HTP DBPC with 5-HTP 100mg tid for 30d in 50 pts. Significant improvement in #s of TPs, subjective pain severity, AM stiffness, anxiety, fatigue low incidence of side-effects Caruso, et al. J Int Med Res. 1990;18:201-209 Cautions with 5-HTP: Cautions with 5-HTP Serotonin syndrome possible if taken with SSRI or MAOI such as Nardil or Parnate Reported with LT@1200mg qd plus MAOI Not reported with 5-HTP@200mg qd plus MAOI Beginning dose 5-HTP@50mg tid suggested Can increase 5-HTP to 100mg tid if response after two weeks is inadequate Cautions with 5-HTP: Cautions with 5-HTP Serotonin syndrome has agitation, confusion, delirium, tachycardia, diaphoresis, BP fluctuation If suspect, discontinue 5-HTP, SSRI, MAOI 5-HTP should not be used with SSRI or MAOI When changing over consider washout period or possibility of serotonin syndrome symptoms Boswellia serrata ~ Salai guggul Frankincense/Indian Olibanum : Boswellia serrata ~ Salai guggul Frankincense/Indian Olibanum Traditional gum resin exudate uses have been for arthritis, abdominal pain, diarrhea, hepatic disorders,neurologic disorders,and as a topical for sores Used in Ayurvedic, Unani and Chinese herbal medicine, commonly used with Ginger, Turmeric, Commiphora, Corydalis in formulae Boswellia serrata ~ Salai guggulPharmacology: Boswellia serrata ~ Salai guggul Pharmacology Studies show that -boswellic acids are specific,non-redox inhibitors of leukotriene synthesis either interacting directly with 5-lipoxygenase or blocking its translocation (but did not affect the 12-lipoxygenase and the cyclooxygenase activities) Ammon HP, Safayhi H, Mack T, Sabieraj J Ethnopharmacol 1993 Mar 38:2-3 113-9 Ammon HP Eur J Med Res 1996 May 24 1:8 369-70 Boswellia serrata ~ Salai guggulPharmacology: Boswellia serrata ~ Salai guggul Pharmacology Inhibits Human Leukocyte Elastase (HLE) a serine protease which initiates injury that triggers the inflammatory process Safayhi H, et al. Inhibition by boswellic acids of human leukocyte elastase. J Pharmacol Exp Ther 281;460-463 Boswellia serrata ~ Salai guggulPharmacology: Boswellia serrata ~ Salai guggul Pharmacology Boswellic acids and triterpene constituents have been shown to inhibit leukemia cells in vitro and induce apoptosis and differentiation Jing Y, et al Chin Med Sci J 1992 Mar 7:1 12-5 Shao Y,et al. Planta Med 1998 May 64:4 328-31 Jing Y, et al. Leuk Res 1999 Jan 23:1 43-50 Boswellia serrata ~ Salai guggulClinical Applications: Boswellia serrata ~ Salai guggul Clinical Applications Recent studies have demonstrated efficacy in models of inflammation and as an analgesic Reddy GK et al. Studies on the metabolism of glcosaminoglycans under the influence of new herbal antiinflammatory agents. Biochemical Pharmacology, Vol 38(20), 3527-3534, 1989 Ammon et al. Mechanism of antiinflammatory actions or curcumin and boswellic acids.J Ethnopharmacol 1991 May-Jun 33:1-2 91-5 Boswellia serrata ~ Salai guggulClinical Applications: Boswellia serrata ~ Salai guggul Clinical Applications Ulcerative colitis(Grade II,III) (350 mg tid for 6 weeks) on stool properties, histolopathology and scan microscopy of rectal biopsies, blood parameters including Hb, serum iron, calcium, phosphorus, proteins, total leukocytes and eosinophils was studied. Patients receiving sulfasalazine (1 g thrice daily) served as controls. All parameters tested improved after treatment with Boswellia serrata gum resin, the results being similar compared to controls: 82% out of treated patients went into remission; in case of sulfasalazine remission rate was 75%. Eur J Med Res 1997 Jan 2:1 37-43 Boswellia serrata ~ Salai guggulDosage and Side-Effects: Boswellia serrata ~ Salai guggul Dosage and Side-Effects Antiinflammatory: 200mg TID as Boswellia serrata extract containing 60-70% organic acids or 50mg TID if standardized to boswellic acids( 100%) Free of typical NSAID toxicity, well-tolerated, no GI or kidney complaints Boswellia serrata ~ Salai guggulClinical Applications: Boswellia serrata ~ Salai guggul Clinical Applications In veterinary medicine has been used for disabling OA ,chronic post-operative knee arthritis, general stifle problems, sore backs, bowed tendons and bone spurs McCrea B. Ancient Indian Herb proving itself a winner for modern day equine athletes. J Am Hol Vet Med Assoc 12(1),19 Boswellia serrata ~ Salai guggulClinical Applications: Boswellia serrata ~ Salai guggul Clinical Applications Bronchial asthma In a double-blind, placebo-controlled study forty patients, 23 males and 17 females in the age range of 18 - 75 years having mean duration of illness, bronchial asthma, of 9.58 +/- 6.07 years were treated with a preparation of gum resin of 300 mg thrice daily for a period of 6 weeks. 70% of patients showed improvement of disease as evident by disappearance of physical symptoms and signs such as dyspnoea, rhonchi, number of attacks, increase in FEV subset1, FVC and PEFR as well as decrease in eosinophilic count and ESR. In the control group of 40 patients 16 males and 24 females in the age range of 14-58 years with mean of 32.95 +/- 12.68 were treated with lactose 300 mg thrice daily for 6 weeks. Only 27% of patients in the control group showed improvement. The data show a definite role of gum resin of Boswellia serrata in the treatment of bronchial asthma. Eur J Med Res 1998 Nov 17 3:11 511-4 Gugulipid ~ Commiphora mukulMukul Myrrh Tree: Gugulipid ~ Commiphora mukul Mukul Myrrh Tree Traditional uses in Ayurveda include lipid disorders, obesity and “ coating and obstruction of channels” With descriptions from the Ayurvedic medical classic Sushrutasamhita as guidance, discovery of lipid lowering and anti-inflammatory effects were made The oleoresin is referred to as guggulu or gum guggul Gugulipid ~ Commiphora mukulPharmacology: Gugulipid ~ Commiphora mukul Pharmacology Gum Guggul lowers VLDL and LDL cholesterol while increasing HDL Aids in regression of atherosclerosis, promotes fibrinolysis, mild platelet aggregation inhibition Khana DS, et al.: A biochemical approach to anti-atherosclerotic action of Commiphora mukul. Indian J Med Res 57, 900-906, 1969 Gugulipid. Drugs Future 13, 618-619, 1988 Singh V, et al.: Stimulation of LDL receptor activity in liver membrane of guggulsterone treated rats. Pharmacol Res 22, 37-44, 1990 Gugulipid ~ Commiphora mukulPharmacology: Gugulipid ~ Commiphora mukul Pharmacology Stimulates thyroid metabolism Triapthi YB, et al.: Thyroid stimulatory action of (Z)-guggulsterone: Mechanism of action. Planta Medica 54, 271-277, 1988 Gugulipid ~ Commiphora mukulPharmacology: Gugulipid ~ Commiphora mukul Pharmacology Anti-inflammatory in acute/chronic models, thought to be due to inhibition of delayed hypersensitivity reactions In models of chronic inflammation shown to be more effective than hydrocortisone, phenylbutazone and ibuprofen in 2 lesions Sharma JN: Comparison of the anti-inflammatory activity of Commiphora mukul with those of phenylbutazone and ibuprofen in experimental arthritis induced by mycobacterial adjuvant. Arzn.-Forsch 27, 1455-1457, 1977 Gugulipid ~ Commiphora mukulClinical Applications: Gugulipid ~ Commiphora mukul Clinical Applications Most effective in inherited hyperlipidemias IIb (LDL,VLDL,TG) and IV ( VLDL,TG) Gugulipid ~ Commiphora mukulDosages: Gugulipid ~ Commiphora mukul Dosages Gugulipid, the standardized extract of gum gugul, based on guggulsterone content ~5% Hyperlipidemia: 500 mg TID Anti-inflammatory: 500 mg QID Agarwal RC, et al.: Clinical trial of gugulipid, a new hypolipidemic agent of plant origin in primary hyperlipidemia. Indian J Med Res 84, 626-634, 1986 Nityanand S, et al.: Clinical trials with gugulipid, a new hypolipidaemic agent. J Assoc Physicians India 37, 321-328, 1989 Gugulipid ~ Commiphora mukulToxicity: Gugulipid ~ Commiphora mukul Toxicity Side-effects occur primarily with crude gum guggul, alcohol and/or petroleum ether extracts: skin rashes, diarrhea, abdominal discomfort No other adverse effects have been noted on liver function,kidney function,blood sugar, or hematological parameters Considered safe in pregnancy LD50 in mice 1,600mg/kg PO or IP Hawthorne Crataegus oxyacantha(spp): Hawthorne Crataegus oxyacantha(spp) Traditionally used as a heart tonic and mild diuretic in CHF, angina, and hypertension in the West, for food stagnation and as a vascular tonic(more recently) in the East Chemical constituents include anthocyanidin and proanthocyanidin flavonoids(quercitin,vitexin) cardiotonic amines(phenylethylamine, tyramine) and triterpene acids(ursolic, oleanolic, crataegolic acids) Hawthorne ~ Crataegus oxycanthaPharmacology: Hawthorne ~ Crataegus oxycantha Pharmacology Due to flavonoid content and “Vitamin P” activity is synergistic with Vitamin C Collagen-stabilizing activity reinforcing natural cross-linking of collagen prevention of free-radical injury due to scavenging of free-radicals inhibition of inflammation by preventing release and synthesis of PGs, leukotrienes, histamine and serine proteases Hawthorne ~ Crataegus oxycanthaPharmacology: Hawthorne ~ Crataegus oxycantha Pharmacology Cardiovascular effects reduces blood pressure, prevents cholesterol deposition in arterial walls improves blood supply to the heart by dilating coronary vessels, reduces lactic acid, relieves angina Petkov V: Plants with hypotensive, antiatheromatous and coronary dilating action. Am J Chin Med 7, 197-236, 1979 Ammon HPT and Handel M: Crataegus, toxicology and pharmacology. Planta Medica 43, 209-239, 1981 Hawthorne ~ Crataegus oxycanthaPharmacology: Hawthorne ~ Crataegus oxycantha Pharmacology Cardiovascular effects improves myocardial metabolism, improves functional contractility, has a positive inotropic effect inhibits angiotension-converting enzyme Blesken R: Crataegus in cardiology. Forsch Med 110, 290-292. 1992 Leuchtgens H: Crataegus Special Extract WS 1442 in NYHA II heart failure. Forsch Med 111, 352-354. 1993 Hawthorne ~ Crataegus oxycanthaPharmacology: Hawthorne ~ Crataegus oxycantha Pharmacology TCM use of resolving food stagnation, due to meat or greasy food, with abdominal distension, pain, or diarrhea likely to due inhibition of Shigella spp.,Pseudomonas aeruginosa, and hypolipemic effects Shanthi S, Parasakthy K, Deepalakshmi PD, Devaraj SN. Hypolipidemic activity of tincture of Crataegus in rats. Indian J Biochem Biophys 1994 Apr 31:2 143-6 Hawthorne ~ Crataegus oxycanthaClinical Applications : Hawthorne ~ Crataegus oxycantha Clinical Applications Can be used in arthritis, atherosclerosis, soft-tissue inflammation, periodontal disease, collagen vascular diseases Specific for atherosclerosis, hypertension, congestive heart failure(NYHA II), arrhythmias Biochem Pharm 33 3491-3497, 1984 The effect of procyanidolic oligomers on the composition of normal and hypercholesterolemic rabbit aortas Planta Medica 43, 313-322, 1981 Crateagus Pharmacodynamics and pharmacokinetics Hawthorne ~ Crataegus oxyacanthaDosage: Hawthorne ~ Crataegus oxyacantha Dosage Crataegus berries or flowers: 3-5g or as an infusion TID Crataegus tincture (1:5): 4-5 ml TID Crataegus fluid extract (1:1): 1-2 ml TID Crataegus freeze-dried berries: 1-1.5 g TID Crataegus flowers SE ( 1.8% vitexin 4’-rhamnoside or 20% procyanidin): 100-250mg TID Hawthorne ~ Crataegus oxycanthaToxicity: Hawthorne ~ Crataegus oxycantha Toxicity Purified proanthocyanidins have been shown to be nonmutagenic by the Ames test Overall toxicity is low LD50 in rats is 25ml/kg with tincture PO, chronic administration is ~5ml/kg Part II : Herbal medicines for Specific Conditions: Part II : Herbal medicines for Specific Conditions Fibromyalgia Neuropathic Pain Osteoarthritis Visceral Pain Herbal Medicines for Fibromyalgia: Herbal Medicines for Fibromyalgia Hypericum : standardized to hypericin and hyperforin content; 600mg BID PC Magnesium: 200-300mg BID to tolerance Malic acid: 200-300mg BID If insufficient response add 5-HTP 100mg QD-TID If sleep problems are still present after 2 weeks consider sleep aids such as melatonin, kava, zizyphus, valerian Herbal Medicines for Neuropathic Pain : Herbal Medicines for Neuropathic Pain Hypericum: standardized to hypericin and hyperforin content; 600mg BID PC Kava: 500mg-1g TID/HS to tolerance Magnesium: 200-300mg BID to tolerance Corydalis 3-9g in divided doses Boswellia 200mg TID Gingko 120-360mg in divided doses Address underlying causal factors if known High index of suspicion for impaired glucose tolerance/DM Herbal Medicine for Visceral Pain: Herbal Medicine for Visceral Pain Gastritis, peptic or duodenal ulcer: Deglycyrrhinated Licorice(DGL); 200-300mg TID 15’ AC Cardiac Pain Crataegus, OPCs, Ginger, Mg, Guggulipid, Cayenne Abdominal pain Corydalis, Curcumin, Boswellia, Ginger, Licorice Herbal Medicine for Tendon and Ligamentous Pain: Herbal Medicine for Tendon and Ligamentous Pain Flavonoids for collagen-stabilizing effects: oligoproanthocyanidins(OPCs) from Crategus, grape seed extracts, berries, pine bark Curcumin/Boswellia 200mg TID Bromelain 500mg TID for acute injury Corydalis 3-9g QD in divided doses Consider HPA dysfunction for chronic problems Herbal Medicines for Joint Pain: Herbal Medicines for Joint Pain Boswellia: 200mg TID Guggulipid 500mg TID Turmeric: 500gm TID OPCs: 50mg TID Bromelain 500mg TID/QID Glucosamine sulfate 1g BID/TID MSM (methylsulfonylmethane) 1-4g BID Suggested Bibliography: Suggested Bibliography German Commission E Monographs, Herb Research Foundation, 1999 Herbal Medicine, Rudolph Weiss,M.D. Green Pharmacy: A History Of Herbal Medicine, Barbara Griggs, 1981 HerbalGram, Herb Research Foundation Textbook of Natural Medicine, Murray and Pizzorno,1999 Healing Power of Herbs, Michael Murray ND, 1995 Resources for Herbal Medicines: Resources for Herbal Medicines Pure Encapsulations: 800-753-2277 Qualiherb/Finemost: 800-533-5907 Vital Nutrients: 800-328-9992 Thorne Research: 800-263-1337 Tyler Encapsulations: 800-869-9705 Lotus Herbs: 626-916-1070
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