Complementary Health and Dietary Supplements PDF

Complementary Health and Dietary Supplements Dental Pharmacology DDS 6215 Dr. Dan Skaar [email protected] Agenda Complementary health approaches – Dietary supplements Natural products – Use – Regulation Frequently used natural products Probiotics Use of Complementary Health Approaches Complementary h...

Complementary Health and Dietary Supplements Dental Pharmacology DDS 6215 Dr. Dan Skaar [email protected] Agenda Complementary health approaches – Dietary supplements Natural products – Use – Regulation Frequently used natural products Probiotics Use of Complementary Health Approaches Complementary health approaches – $34 billion+ spending – 33% of adults (NHIS 2012) – 12% of children Dietary supplements – Vitamins and minerals – Natural products Herbs – Natural product use (2012 NHIS) $13 billion spending 18% of adults 5% of children Natural Product Use Natural Product Use Trends Natural Product Use Increases with – – – – – Age Comorbidities Women (all age groups) Education Income Dietary Supplement Safety Reporting Regulation Dietary Supplement Health and Education Act (DSHEA) 1994/1998 – Increasing market – Promotion of maintenance of health using structure/function claims – Permits but does not require safety precautions – Manufacturers to substantiate claims if challenged – FDA authorization to create good manufacturing practices (GMP) Regulation FDA role – Product introduction exempt from review – Remove unsafe products from market E.g. ephedrine alkaloids (2004) – “Innocent until proven guilty” Action only if “significant or unreasonable” risk to consumers Ban product only if an “imminent hazard” – Publish GMPs Regulation DSHEA defines “dietary supplements” as: – Including vitamins, minerals, herbs and amino acids – Can’t be represented as a food or drug – Label as dietary supplement – Formulated as capsule, tablet, powder, liquid or gel Office of Dietary Supplement Programs (2015) Regulation Dietary supplement claims – Express disease claims not allowed “Treats diabetes” – Implied disease claims not allowed “Controls blood sugars” – Express and implied disease claims made by the name of the product or in pictures/symbols “Migraine-B-Gone” “Cold-Away” Regulation Dietary supplement claims – Health maintenance claims allowed “Maintains a healthy urinary tract” “Gives you energy” – Common, minor symptoms associated with life stages are not diseases; claims can be made – Hot flashes – PMS – Mild acne - Wrinkles - Mild memory loss of aging Regulation All claims must be accompanied by a packaging disclaimer: “This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.” Nongovernmental Evaluation USP Dietary Supplement Verification Program (DSVP) – Tests products that are submitted voluntarily by manufacturers Consumerlab.com – Independent company that tests dietary supplements – Seal of approval Impurities & Adulterants Contaminants found in herbal remedies – Microorganisms Staph aureus, E. coli, Salmonella, Shigella, Pseudomonas Lead, mercury, arsenic Digitalis, belladonna alkaloids NSAIDs, corticosteroids, warfarin, thyroid extracts, testosterone – Pesticides – Toxic metals – Botanicals – Drugs Contaminants in non-herbal remedies – Animal-origin products (diseased animals); bovine sources (Mad cow disease) NEJM 2002;347:2046-56. Impurities & Adulterants Treat muscle pain, arthritis, osteoporosis – “impurities include dexamethasone and diclofenac – Not revealed in labeling FDA voluntary recall FDA warning of relabeling and resold as “WOW” on web Impurities & Adulterants Hyland Teething products – FDA warning and request to recall Inconsistent levels of belladonna Children < two years old Pharmacologic effect _______ Frequently Used Natural Products Fish oil/Omega 3 “4 Gs” – – – – Gingko Garlic Ginseng Ginger Melatonin St John’s Wort Kava Echinacea Fish Oil Omega-3 Fatty Acids Indications – – – – ↓ risk of CAD Hypertriglyceridemia Hypertension Secondary prevention 2012 JAMA questions MOA – Eicosanoid precursors Dosing – 1-4 gms fish oil qd Adverse experiences – GI discomfort – Bleeding Ginkgo World’s oldest living tree species – Medicinal use for > 1000 years Indications – Alzheimer’s and age related dementia Modest improvement MOA – Terpenoids and flavonoids Modulate neurotransmitter activity Vasodilator Inhibit platelet activating factor Dosing – 120 – 240 mg qd – Response in weeks Ginkgo biloba Ginkgo Adverse experiences – Dizziness, GI upset, headache, palpitations – Bleeding – Lower seizure threshold Drug interactions – CYP450 effects: 2C9 (strong inhibition) 3A4 (conflicting information) Dental/Misc – D/C prior to surgery (>36 hr) – Increased bleeding risk if taken with: Aspirin/NSAIDS Warfarin Garlic (Allium sativum) Indications – Hypertension ↓ BP vs. placebo: 7/5 mmHg (2-7%) – Hypercholesterolemia and atherosclerosis ↓ TC vs. placebo: 16-23 mg/dl (4-12%) MOA – Allicin (active) Antiplatelet (interferes with thromboxane synthesis) Inhibits HMG-CoA reductase Antibacterial, anti-inflammatory, antioxidant Dosing – Varies by raw, powder and extract forms Garlic Adverse experiences – GI irritation, heartburn – Breath & skin odor – Bleeding Drug Interactions – May induce CYP 3A4 – May ↑risk of bleeding with warfarin/ASA and antiplatelet drugs Dental/Misc. – D/C 7-14 days prior to dental sx Ginseng Indications – Stress and restores homeostasis – Lower postprandial glucose MOA – Ginsenosides with heterogenous effects Steroid-like actions Inhibit platelet aggregation Dosing – Varies by powder and extract – Limit use to 3 consecutive months Ginseng Adverse experiences – Hypoglycemia – Bleeding – Ginseng abuse syndrome Drug Interactions – Warfarin Dental/Misc. – D/C 7-14 days prior to dental sx Melatonin Indications – Insomnia and jet lag Reduce time to sleep Less evidence on sleep time and quality – Cancer and chemotherapy MOA – Regulate sleep cycle Dosing – 0.5- 5 mg (insomnia) Melatonin Adverse experiences – Dizziness – Headache Drug interactions – Sedatives Dental/Misc – Increase immune function Interfere w immunosuppressive therapy St. John’s Wort (Hypericum perforatum) Indications – Mild to moderate depression – Anxiety MOA – Hypericin and hyperforin Inhibits serotonin, norepi, dopamine reuptake Dosing – 600 - 1200 mg qd – Can have withdrawal reactions → taper dose – Comparable effectiveness to low doses of TCAs and SSRIs St. John’s Wort Adverse experiences – Photosensitivity – GI nausea, diarrhea – Confusion, drowsiness, dizziness, irritability – Xerostomia St. John’s Wort Drug Interactions – Increase metabolism of many drugs Potent CYP 3A4 inducer (double activity) – Alprazolam – CYP 2C9 inducer ↓ [ ] of NSAIDs (e.g. ibuprofen), warfarin – CYP 1A2 inducer (less than 3A4) – Induces P-glycoprotein transporter ↓ [digoxin] levels by 25% St. John’s Wort Dental/Misc. – Increases risk of serotonin syndrome and other CNS reactions Use with caution if taking psychotropic drugs (TCA, SSRI) – Avoid in pregnancy due to teratogenic risk Kava Indications – Anxiolysis and sedation MOA – Kavalactones Potentiate GABA inhibitory transmission Dosing – Max 250 mg qd Kava Adverse experiences – Kava dermopathy with heavy use Scaly cutaneous eruptions – Hepatotoxicity Drug interactions – Potentiate other sedatives Dental/Misc. – Caution if prescribing for anxiolysis D/C 1 -2 days Kava powder Echinacea (Echinacea purpura) Indications – Treatment of URIs and colds Est. 10-30% ↓ severity & duration – Prevention of viral respiratory infections (colds) Ineffective MOA – Immunomodulator (cell-mediated immunity) Dosing – Dose varies widely depending on the product 7-10 days starting with cold symptoms Long-term (< 8 weeks) Echinacea Adverse experiences – GI upset – Hepatotoxicity – Unpleasant taste Drug interactions (CYP3A4) – Avoid/caution with hepatotoxic drugs Acetaminophen – Avoid with immunosuppressant drugs Dental/Misc. – Immunosuppression with long term use (> 8 weeks) Risks Colloidal Silver FDA ruled ineffective and unsafe in 1997 Indications – Natural antibacterial Skin and respiratory infections Gum disease – Prevent colds and flu – Pregnancy MOA – Unknown function – Purported to strengthen immune system Inhibit bacterial enzymes Protein binding Colloidal Silver Dosing – Topical and oral administration Adverse experiences – Argyria Blue-gray skin and membrane discoloration – Irreversible – Kidney and liver Risk Natural tree native to SE Asia Used in tea to ease opioid withdrawal, fatigue, pain, cough and diarrhea MOA – Interaction with opioid receptors Contamination – Salmonella Risks Considerations Prior to Dental Procedures Increase Bleeding Risk Fish Oils Four “Gs” – – – – Gingko Garlic* (high doses) Ginger (> 1 gm qd) Ginseng* Other Risks Echinacea – Immunosuppressant Kava – Sedative effect – Hepatotoxicity (APAP) St. John’s Wort – Drug interactions – Hepatotoxicity (APAP) Feverfew* Evening Primrose (3 gm qd) Valerian – Sedative effect Vitamin E (> 400 IU qd) * Irreversible platelet inhibition Probiotics Formulations of living/vital microorganisms – Confer health benefit to host – Common use in U.S. Lactobacillus Bifidobacterium World market – $24 B sales (2011) lactobaccillus Probiotics Availability – Dairy foods – Beverages – Dietary supplements U.S. regulation – FDA Regulate as drug, dietary supplement or food No approved health claims Probiotics Uses – Gastrointestinal – Oral Mechanisms of effect – Influence mucosal integrity – Produce antimicrobial/ physiologic compounds – Immunomodulatory Probiotics Studies – Methodological limitations- early studies – Strong clinical evidence lacking – Safety data limited Long-term – Some formulations show promise science? Oral Probiotics Clinical uses – – – – – – Caries Gingivitis Periodontitis Reduce plaque Halitosis Teeth whitening – – – – Lozenge Mouthwash Mints Tablets Availability Oral Probiotics Mechanisms of effect – Compete for tooth and tissue adhesion sites – Modify local oral environment Alter pH – Produce antimicrobial compounds – Stimulate immune response Oral Probiotics Caries prevention – Bacteria adhere to tooth and integrate into biofilm Compete/antagonize cariogenic bacteria Lactobacilli S. mutans – Conclusive study results lacking Oral Probiotics Periodontal disease – Bacteria proposed to Inhibit periodontal pathogen growth Prevent superinfection Promote immune response Study results remain inconclusive Oral Probiotics Periodontal product – Proprietary mix of 3 bacteria S. viridans strains Dissolvable tablet – Bacteria release H2O2 – Bleaching effect Summary Dietary supplements including natural products widely used Government regulation of dietary supplements far less than for Rx drugs – DSHEA regulations – FDA role Clinical effects of natural products often have minimal evidence or are unproven