Food Supplements and Herbal Medicine Case Study 2. Dr. Lalita Kaul Professor Department of Community & Family Medicine

Transcription

1 Food Supplements and Herbal Medicine Case Study 2 Dr. Lalita Kaul Professor Department of Community & Family Medicine

2 Integration of Herbal Remedies in Clinical Practice TABLE 1: GUIDELINES FOR THE USE OF HERBAL REMEDIES IN CLINICAL PRACTICE All patients should be asked about use of herbal remedies and dietary supplements Natural does not necessarily mean safe Herbal/pharmaceutical interactions do occur; therefore know the literature and about interactions Lack of standardization of herbal agents may result in variability among manufacture and potential misidentification of plant species Herbal treatments should not be used if the patient is contemplating pregnancy of during pregnancy of lactation because of lack of long-term clinical trials proving safety Herbal treatments should not be used in dosages higher than those recommended Herbal treatments with known adverse effects and toxic effects should be avoided Infants and children should not use herbal treatments; elderly patients should exercise caution and be closely monitored An accurate diagnosis and discussion of proven treatment options are essential before considering herbal treatments Adverse effects should be documented in the patient s chart, therapy discontinued, and the Food and Drug Administration notified using Med Watch Clinicians should maintain Continuing Medical Education (CME) in herbal supplemental or develop professional relationships with competent health care providers to which patients can be referred Maintain appropriate resources, including such items as PDR for Herbal Medicine, German Commission E Report, and Pharmacist s Letter Natural Medicine s Comprehensive Database SOURCE: Adapted from Cirigliano M, Sun A. Advising patients about herbal therapies, JAMA 1998;280:

3 Herbal Remedies: Patient Assessment All patients seen by health care providers should be queried regarding the use of all forms of alternative or complementary therapies. May prevent potential drugherb interactions Emphasizes that just because something is natural, does not guarantee safety Allows the health care provider to assess whether supplements taken are beneficial

4 Drug-Herb Interactions TABLE 2: SELECTED DRUG HERB INTERACTIONS Dong Auai/warfarin HERB AND DRUG Siberian ginseng/digoxin Garlic/warfarin Gingko biloba/asa/warfarin Ginseng/warfarin St. John s wart /SSRIs /OCTs /Indinavir /cyclosporine Yohimbine/tricyclic antidepressants RESULTS OF INTERACTION Increased INR and bruising Raised digoxin concentrations Increased INR Spontaneous bleeding Decreased INR Serotonin syndrome/decreased serum drug levels Hypertension SOURCE: Adapted from Fugh-Berman A. Herb-drug interactions. Lancet2000;355:

5 Contraindications for the Use of Herbal Treatments in Special Populations Herbal treatments should be taken under the supervision of a physician or other qualifies health care professional Future research evaluating the safety and efficacy of the use of herbal treatments in special populations is warranted Children, Elderly, etc. Biological changes associated with aging could significantly alter their bioavailability and clinical responsiveness in this population. Based on the lack of studies related to product safety during pregnancy leaves potential harms unknown Studies involving herbal treatments don t evaluate the long-term effects; therefore, clinical monitoring is advised Herbal remedies are not without risks Herbal remedies containing tannins Found throughout nature Have been documented to increase the risk of certain oropharyngeal cancers with long-term exposure

6 Selected Potentially Toxic Herbals TABLE 3: SELECTED POTENTIALLY TOXIC HERBALS HERB POTENTIAL TOXICITY Pheasant s eye Cardiac Arrest Arnica GI/muscle toxicity Pennyroyal Yohimbine Mistletoe Hepatotoxicity Hypertension GI bleeding/cns Toxicity SOURCE: Adapted from Yarnel E. Meserole L. Toxic Botanicals: is the poison in the plant or its regulation? Alternative and Complementary Therapies 1997;3(1):13019

7 Selected Potentially Toxic Herbals (Cont.) A number of herbal remedies have documented liver toxicity Herbal have been known to cause toxicity to a variety of organ systems The liver appears to be the most common target organ for serious herbal toxicity Patients who wish to use herbal remedies may want to seek the advice of an herbalist or traditional Chinese medicine practitioner Current regulations with regard to licensing may make referrals difficult, leaving the physician left to rely on word of mouth

8 Herbal Supplements Associated with Hepatic Injury TABLE 4: HERBAL SUPPLEMENTS ASSOCIATED WITH HEPATIC INJURY HERB CLINICAL MANIFESTATIONS PATHOLOGIC FINDINGS Chaparral ALT/AST elevations Acute and chronic liver injury Portal inflammation Jin Bu Huan ALT/AST elevations Acute and chronic liver injury Germander ALT/AST elevations Acute and chronic liver injury Mistletoe ALT/AST elevations Acute and chronic hepatitis Comfrey ALT/AST elevations Hepatic veno-occlusive disease Pennyroyal ALT/AST elevations Acute liver injury SOURCE: Adapted from Bashir RM, Lewis JH. Hepatotoxicity of drugs used in the treatment of gastrointestinal disorders. Gastroenterology Clin North Am 1995;24:

9 Reporting Adverse Events Manufacturers of herbal supplements are not required to report adverse events Med Watch, the Food and Drug Administration s (FDA) medical products reporting program, was designed to enable health care professionals to voluntarily report adverse events and product problems. The purpose is to identify problems associated with herbal remedies from the community and to report them to the medical community

10 STEPS to Reporting Adverse Events Report problem to Med Watch ( atch) Once the potential problems or adverse event is identified, the FDA can initiate one of the following: Labeling change Boxed warning Product recalls and withdrawals Medical and Safety Alerts Label change Boxed Warning Product Recalls Safety Alerts

11 Popular Herbal Remedies A number of herbal remedies are commonly self-prescribed by patients The most popular and well researched of these are presented as a basic primer with regard to use, potential toxicity, and efficacy based on scientific analysis follows this slide.

12 American Ginseng (Panas Quinquefolius) Indications Pharmacology Scientific Analysis Adverse Effects Summary Ginseng consumption in the US is for the increase of energy Adaptogenic Agent ginseng increases the body s ability to adapt to both emotional and physical stress In Chinese medicine, ginseng is used to restore vital energy (qi or chi) American Ginseng is sought to be a calming herbal Ginsenosides are thought to be the most important chemical entities responsible for American Ginseng s effects Several Studies have revealed: Hypoglycemic effect along with a decrease in prolactin levels Facilitation in task behavior in memory-compromised animals with ant cholinergic-induces amnesia Possess antioxidant properties No significant adverse effects have been reported Used as an adaptogenic agent Mixed results in clinical trials make recommendations difficult Has continued for thousands of years

13 Asian Ginseng (Panax Ginseng) Indications Pharmacology Scientific Analysis Adverse Effects Summary Adaptogenic Agent ginseng increases the body s ability to adapt to both emotional and physical stress Used to boost energy stamina More stimulating than American ginseng Used for thousands of years in Chinese traditional medicine Asian ginseng has been shown to have antiplatelet, vasodilator, and cytoprotective effects against ischemia and toxins Large number of RCT have been performed Yielding mixed results Literature does not suggest any significant benefit toward enhancing physical performance No benefits in memory, concentration and cognitive function have been noted Minimal side effects have been reported. Has the potential to interact with warfarin The efficacy of Asian ginseng has not been established beyond a doubt for any indication

14 Black Cohosh (Cimicifuga Racemosa) Indications Commonly used for menopausal symptoms as an alternative to hormone replacement therapy Pharmacology Active ingredients include the triterpene glycosides Studies have failed to show estrogenic properties Scientific Analysis A number of clinical trials have revealed contradictory results with regard to treatment and efficacy of menopausal symptoms Adverse Effects Minimal gastric distress occurs, but black cohosh is usually well tolerated Summary Several studies show benefit in the treatment of menopausal symptoms Data are contradictory and no impact on bone density have been found

15 Soy Protein Phytoestrogens Indications Pharmacology Scientific Analysis Adverse Effects Summary Used as treatment for hot flashes Alternative to hormone replacement therapy Shown to modestly lower total cholesterol and low density lipoprotein cholesterol levels in both hypercholesterolemia and normocholesterolemic men and women Soy isoflavones are nonsteroidal molecules that have structural similarity to estradcoil-17-β Studies have shown: A significant reduction in menopausal not flashes and serum cholesterol Modest increase in bone density Data regarding efficacy in reducing cholesterol levels is strong with intake of greater than or equal to 25 g soy protein per day Safety concerns are being debated Study using rats with low levels of endogenous estrogen have shown a higher incidence of breast cancer risk with long-term isoflavone use Studies suggest a protective effect in animals with normal levels of endogenous estrogen No human studies have been performed outlining health risk. Although limitations in research conducted, physicians believe its safe to use as an alternative to hormone replacement therapy for hot flashes More data is needed to assess risk associated with using isoflavone supplements Soy protein is indicated for use in reducing cholesterol levels FDA has approved a health claim or products containing 6.25 g soy protein per serving

16 Chamomile (Matricaria Recutita) Indications Pharmacology Scientific Analysis Adverse Effects Summary Used as an anti-inflammatory, antispasmodic, and calming agent Used topically to treat inflammatory skin and mucous membrane disorders Active ingredients include the terpenoids Can inhibit the inflammatory mediators of the arachidonic acid cascade such as 5-liposygenase and cyclo-oxygenase A number of clinical trials have shown benefit as an antispasmodic and for colic A small study showed sedative effects Chamomile is generally regarded as a mild and safe herb Allergic reactions can occur in patients who are allergic to ragweed Chamomile appears to be mild and generally safe for the treatment of colic and anxiety Used often as a topical agent for skin disorders

17 Echinacea [Echinacca Species (spp)] Indications Pharmacology Scientific Analysis Adverse Effects Summary Used for the treatment of mild upper respiratory infections Alkyl amides, caffeic acid derivatives and echinacosides are thought to be the most important constituents Oral preparations appear to enhance nonspecific phagocytosis by stimulating leukocyte function and enhancing T-cell function Several well designed studies have shown that echinacca has a role in the prevention of the common cold No data exist that supports the notion that echinacca reduces flu like illness Echinacca preparations are generally well tolerated Use in patients with autoimmune illness is contraindicated due to its immune stimulating effects Although the use of echinacca to prevent colds has not been proven, a number of studies do show a shortened length of illness while taking it

18 Ephedra (Ma Huang) Indications Pharmacology Scientific Analysis Adverse Effects Summary Used for asthma and nasal congestion Has become popular as a stimulant and energizer for weight loss Combined with guarana (which contains light levels of caffeine) for weight loss The most important constituents of ephedra are the alkaloids pseudoephedrine and ephedrine Clinical trials are well established Herbal weight loss preparations have used the combination of ephedra with guarana, leading to modes weight loss through the mechanism of increased theramogenesis The results are minimal at best and are effective when combined with diet and exercise High doses can induce hypertension, arrhythmias, nervousness, tremor, insomnia, and tachycardia Several deaths have been reported Product has been banned in many international markets Data show benefit for weight loss when combined with a reduced-calorie diet and exercise Potential serious side effects can occur, and deaths have been reported Use of ephedra is not recommended

19 Ginger (Zingiber officinale) Indications Pharmacology Scientific Analysis Adverse Effects Summary Used as a digestive aid for mild dyspepsia Used to treat and prevent nausea and motion sickness Active compound include the phenolic compounds gingerol and shogaol Act as an antioxidant, prostaglandin, and leukotriene inhibitor and to inhibit platelet aggregation Results of human pharmacologic studies have shown: Variable results Statistically significant effects in the treatment of motion sickness and as an antiemetic Has no known clinical adverse effects other than heartburn, which occurs rarely Study show significant results in the use of ginger in treating nausea and motion sickness

20 Garlic (Allium Sativum) Indications Pharmacology Scientific Analysis Adverse Effects Summary Used in various cultures Used to treat infections, heart disease, diabetes Used as an antithrombotic agent and antioxidant Contains active sulfur compounds including alliin and allicin Allicin stimulates fibronolysis, inhibits arachidonic acid conversion, reduces platelet aggregation Epidemiologic studies have suggested that people who eat garlic and onions have lower lipid and cholesterol levels Data exists regarding garlic and its use for hypercholesterolemia and hypertension Evidence for garlic s beneficial effects on cholesterol and blood pressure is inconsistent Many studies have shown positive as well as negative effects Can cause malodorous breath and body odor Dyspepsia, flatulence, anorexia, dermatitis have occurred Allergic reactions have been noted in the literature Garlic supplementation should be considered a possible risk factor for bleeding Garlic supplementation appears safe for most patients who wish to use a natural product for cardiovascular health Long-term beneficial effects have not been well established

21 Gingko Leaf Extract (Gingko Biloba) Indications Pharmacology Scientific Analysis Adverse Effects Summary Used to improve cognitive function in the elderly Used to treat dementia, including Alzheimer s Used to treat conditions associated with vascular insufficiency including intermittent claudification Used to treat premenstrual syndrome (PMS) The Mechanism action is still not completely understood The flavinoids in the gingko leaf have antioxidant properties that protect tissues from oxidative damage Scientific evidence indicates gingko in improving cognitive function, particular short term visual memory in nondemented patients Article in JAMA, reported no significantly measurable benefit from this herb The National Center for Complementary and Alternative Medicine (NCCAM) 5-year study of 3000 people aged 75< to determine if the daily gingko ingestion can prevent dementia in Alzheimer s disease Used safely in clinical trials up to 1 year Reported adverse effects include mild gastrointestinal symptoms, such as constipation, stomach upset, and allergic skin reactions The gingko tree is the oldest living tree species in the world. Most commonly prescribed in Germany, where it is the preferred treatment for dementia More research is needed to confirm the use of gingko to improve memory and cognitive function in otherwise health older adults

22 Milk Thistle (Silybum Marianum) Indications Pharmacology Scientific Analysis Adverse Effects Summary Used as a hepatoprotectant in patients with viral hepatitis as well as alcohol cirrhosis Used in Europe as a treatment for Amanita mushroom poisoning Contains silybin Acts as an antioxidant and inhibits the enzyme 5-lipoxygenase Reduces the inflammatory leukotrienes and limits the activity of Kupffer cells in vitro, which may slow the progression of chronic liver disease 14 randomized controlled trials have evaluated its efficacy and safety Most of the studies were of poor methodological quality Many showed improvement in liver function tests and biopsy-proven cirrhosis No major side effects have been reported for patients using milk thistle Loose stools and other mild gastrointestinal effects may develop in some, but those occur rarely Clearly relevant benefits have not been clearly established Given its safety record and significant lack of drug interactions

23 Conclusion The use of botanical and herbal remedies to reduce the symptoms, treat and prevent chronic disease is on the rise Herbal remedies have potential for interactions with standard pharmaceutical agents as well as inherent toxicities In most cases, herbal remedies are safe and many demonstrate clinical efficacy when used in appropriate settings and in proper dosages With time, a number of herbal remedies may stand the test of scientific study and will add to the clinician s existing armamentarium of medicinal agents available for use in treatment Heath Care professionals are positioned to provide patients with reliable, scientifically sound advice on the use of herbal remedies in addition to a balanced diet