Module 20 - Complementary and Alternative Medicine

Geriatric
Pharmacy Review Module 20 : Complementary and Alterna<ve Medicine
Accreditation Information
ASCP is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
This home study web activity has been assigned 2.5 credit hours. ACPE UPN: 0203-0000-10-049-H01-P Release Date: 4/01/2010 Expiration Date: 4/01/2013
To receive continuing education credit for this course, participants must complete an on-line evaluation form and pass the online assessment with a score of 70% or better. If you do not receive a minimum score of 70% or better on the assessment, you are permitted 4 retakes. After passing the assessment, you can print and track your continuing education statements of credit online.
Geriatric Pharmacy Review courses have not yet been approved for Florida consultant pharmacy continuing education.
Copyright 2011 American Society of Consultant Pharmacists
Content Experts
Current Content Expert: Carla Bouwmeester, PharmD, BCPS Assistant Clinical Professor Northeastern University
Legacy Contributor:
Steven G Ottariano RPh Clinical Pharmacy Specialist Complementary Medicine VA Medical Center
Faculty Disclosure: Carla Bouwmeester has no relevant financial relationships to disclose. Steven G. Ottariano RPh ,has no relevant financial relationships to disclose.
Complementary and Alternative Medicine
Learning Objectives:
By the end of this review concept, you should be able to: Understand the economic, regulatory and societal impact of the use of dietary supplements, especially amongst the senior population. Identify dietary supplements used in the senior population and their most common uses, mechanism of effect, side effects, drug interactions and adverse effects. Apply the evidence base within the geriatric literature to support or refute the safe and efficacious use of a dietary supplement in the senior population. Design a monitoring plan, for both safety and efficacy, for a senior taking a dietary supplement.
Complementary and Alternative Medicine (CAM)

Definitions: Alternative medicine Complementary medicine Integrative medicine Whole medical systems
Complementary and alternative medicine, or CAM, is a collection of health care practices and belief systems that are generally considered to be set apart from Western conventional medicine. By definition, alternative medicine is used in place of conventional medicine whereas complementary medicine combines both conventional and alternative medicine practices. Integrative medicine combines conventional medicine with CAM modalities that have some evidence of safety and effectiveness. Scientific evidence for most CAM therapies however is limited and questions regarding indications, safety, and potential interactions with conventional medicine remain. Whole medical systems are built on complex systems of spiritual belief, philosophy, practical theory, and scientific practice. These systems developed over thousands of years and have evolved apart from the more modern conventional approach to medicine practiced in the United States. Examples of whole medical systems include traditional Chinese medicine, Ayurvedic medicine, and homeopathy.
Homeopathy Theory
Homeopathic remedies are prepared based on the following principles: Law of susceptibility Law of similars Provings Law of infinitesimals Potentiation
Homeopathy was first espoused by a German physician named Samuel Hahnemann in the late 1700s. His theory was based on the idea that highly diluted preparations of substances that cause a particular symptom can be used to treat conditions with similar symptoms. Although homeopathy utilizes natural substances, it is a distinct medical practice and is not synonymous with herbalism, natural medicine, or holistic medicine. Homeopathy takes into account the patients physical and psychological state when evaluating their vital force. The Law of susceptibility refers to the believe that a persons vital force can be disrupted by internal as well as external factors and produce symptoms of disease. Symptoms are evaluated by a homeopath and treated with homeopathic remedies specific for that patient. Homeopathic remedies are commercially available or may be custom-made by a homeopath, however, they are all prepared with a similar philosophy. The Law of similars is based on the idea that like cures like. For example, a substance that causes heart palpitations is used to treat abnormal heart rhythms. Provings are tests done in normal, healthy people to determine the effect of the substance being tested. Detailed records are kept on patient-reported symptoms, physical observations, and other relevant findings to ultimately determine the appropriate indication. Once a substance is identified and proven, the final remedy is prepared via serial dilutions. This practice is based on the Law of infinitesimals which states that only an infinitesimal amount of the original material is needed for the remedy. Related to this belief is the Theory of potentiation which states the more dilute the substance, the stronger and more potent it becomes. Homeopathic remedies undergo a series of dilutions and succession, or vigorous shaking, until the final concentration for the product is achieved.
Homeopathy Remedies
Homeopathic remedies follow a nomenclature to indicate their relative potency. Dilutions of 1/10 are signified by X. Subsequent dilutions are expressed in terms of 2X, 3X, etc. which correspond to 1/100, 1/1000 respectively. Dilutions of 1/100 are signified by C, where 2C=1/10,000 and 3C=1/1,000,000. When dilutions reach 12C or 24X, there is no longer any measurable amount of the original substance. In this case, just the essence of the ingredient remains. All medications listed in the Homeopathic Pharmacopeia of the United States (HPUS) are considered drugs under the Food, Drug and Cosmetic Act and are regulated by the Food and Drug Administration (FDA). Homeopathic remedies however, are often exempt from the rigorous testing for safety and effectiveness that is required for other prescription and OTC medications. The FDA contends that homeopathic remedies contain little or no active ingredient and pose little risk for adverse effects. Homeopathic medicines must be manufactured according to the specifications in the HPUS and most manufacturers are registered with the FDA to ensure good manufacturing processes. Homeopathic remedies are required to list the ingredients, instructions for use, indications, and extent of dilution on the label. Ingredients must be listed even if they are present in undetectable levels. Homeopathic remedies are not required to have an expiration date and are exempt from testing for the identity and strength of the final product.
Traditional Chinese Medicine (TCM)
TCM beliefs are based on the following theories: Qi Channels (meridians) and collaterals Yin and yang Five phases Zang and fu Traditional Chinese medicine, also known as TCM, has its origins over 2000 years ago during the Han dynasty. During this time period physicians used combinations of herbal materials to treat conditions such as fever, the common cold, sore throat, dizziness, and coughing. In the Tang dynasty (618-907AD) the emperor commissioned a compilation of common remedies, or material medica, which cataloged over 800 substances derived from plants, animals, minerals, and metals. This became the basis of what we now consider herbal medicine in the context of TCM. In conjunction with herbal medicines, food therapy is also commonly prescribed. This may involve dietary recommendations or restrictions to promote a healthy diet or restore health and overall balance.
Traditional Chinese Medicine (TCM)
TCM encompasses much more than herbal therapy however, and involves a complex belief system that views the mind, body, and spirit as one whole, incorporating both internal and external forces. Qi is the internal life force or breath that forms the core of TCM philosophy. Qi circulates throughout the body along channels or meridians and associated collaterals. When the flow of qi is interrupted, there is disharmony which may lead to physical symptoms and disease. Related to qi is the concept of yin and yang which are oppositional forces contained within a whole. They are interconnected and continuous as each gives rise to the other. Zang fu relates bodily functions with yin and yang to describe their interactions and connections. For example, zang organs are yin and include the liver, heart, spleen, lung, kidney, and pericardium whereas fu organs are yang and include the large intestine, gall bladder, urinary bladder, stomach, and small intestine. It is important to remember that zang fu organs describe function rather than anatomy. The organs work together to regulate functions of the body and are related to the five phases of wood, fire, earth, metal and water. Diagnosis in TCM involves a thorough examination of the balanced function of the organs as well as the flow of qi. TCM practitioners may start by interviewing the patient to gain an understanding of their symptoms and general emotional and physical health. They may then move on to palpating or touching the body to obtain pulses along various meridians. Diagnosis also involves observing the tongue and listening to or smelling particular areas of the body.
Traditional Chinese MedicineModalities
Traditional Chinese Medicine (TCM) includes the following modalities: Herbal medicine Food therapy Acupuncture Moxibustion Auriculoacupuncture Acupressure Cupping Tui na Qigong
Acupuncture is one of the most well know practices of TCM after herbal medicine. In the 2007 National Health Interview Survey, an estimated 3.1 million adults in the U.S. used acupuncture in the previous year. Acupuncture involves the insertion of thin needles into specific locations on the body along the meridians (see acupuncture map above). Moxibustion is often practiced in conjunction with acupuncture and involves the burning of dried Chinese mugwort above acupuncture sites. The smoldering mugwort is applied to the end of acupuncture needles, rolled into cigarette-like tubes and held over acupuncture sites, or placed in cones which are applied directly to the skin. Moxibustion is believed to increase circulation to the site and provide a warming effect. Also related to acupuncture is the practice of auriculoacupuncture which involves placing needles in specific areas of the ear. The auricle of the ear is thought to have an appearance similar to an inverted fetus. Detailed auricle maps relate areas on the ear to specific structures and functions of the body.
Traditional Chinese MedicineModalities

In addition to acupuncture, TCM utilizes various forms of external manipulation or massage to help restore harmonious relationships within the body. One example of this is tui na which is a form of massage involving acupressure points that has been practiced for more than 2000 years. It utilizes direct massage of acupressure points, realignment of qi along certain channels and collaterals, and manipulation of joints to reset musculoskeletal relationships. Another form of massage is cupping where spherical cups are placed on acupressure points on the back. A match is lit under the sphere and removed before being placed on the back, creating suction as air within the sphere cools. When oil or lotion is applied to the skin the cups can be slid around creating a reverse pressure massage. To promote general health, qigong is a set of ritualized breathing and movement exercises which can also relieve stress and improve the circulation of qi. This may be particularly helpful for the elderly patient.
Traditional Chinese MedicineHerbalism
Qualities of herbs: Nature Taste Affinity Action
The use of herbs in TCM is related to improving the flow of qi and restoring balance to the body. Herbs are usually prescribed in a fixed combination but can also be taken individually or as part of a customized combination. Herbal remedies may contain plant, animal, or mineral constituents (i.e. powdered ginseng, ground deer antler, or oyster shells). Traditionally, dried herbs are prepared as tea, but some Western practitioners also supply herbs in a premixed or pill form to avoid the bitter taste. Each individual herb has specific qualities related to nature, taste, affinity, and primary action. The nature of an herb may be described as either cooling or heating, but may also be called relaxing or energizing. For example, peppermint is cooling and can be used to lower metabolism or reduce gas and bloating. Herbs are also classified by taste and have either sour, bitter, sweet or bland, spicy, or salty qualities. Affinity refers to the zang fu organ system where the herb has the greatest effect, whereas action" describes the primary effect of the herb (i.e., astringe, purge, dispel, or tonify). Note: There is limited evidence-based information on TCM fixed combination herbals. Information regarding side effects, adverse reactions, and interactions can be extrapolated from research done on the individual herbal components, but effectiveness may differ when herbs are used in fixed combinations. Research is underway to examine the effects of fixed combination herbals (for more information, go to http://nccam.nih.gov/research/ ).
Ayurveda
Doshas Vata (wind/spirit/air) Pitta (bile) Kapha (phlegm) Ayurveda evolved in India and is derived from the Sanskrit words ayus and veda which mean the science of life. Ayurveda is based on the five great elements (earth, water, fire, air, and space) which compose the human body and the world around us. The constituent elements of the body can further be classified as chyle, blood, flesh, fat, bone, marrow, and semen. Doshas are the regulating qualities that form the unique characteristics of each person and control bodily functions and activities. Imbalances in the doshas, caused by stress, an unhealthy lifestyle, diet, or bacteria, lead to physical and psychological illness. Such imbalances can be corrected by exercise, healthy eating habits, eliminating impurities, reducing stress, and increasing harmony. Ayurvedic practices include yoga, meditation, massage, dietary recommendations, and herbal therapies. There has been some concern about Ayurvedic remedies being contaminated with heavy metals and potentially toxic ingredients. Therefore, it is important to obtain products from reputable and trusted sources.
Complementary and Alternative Medicine (CAM)Practice Types

CAM practices: Biologically-based Energy medicine Manipulative and body-based Mind-body medicine
CAM practices can be divided into four broad categories which may overlap: biologically-based, energy medicine, manipulative and body-based, and mind-body medicine. Biologically-based practices include adding dietary supplements, functional foods, or any other supplements to a persons diet. Energy medicine is based on the belief that each person has a subtle form of energy that becomes disturbed or out of balance in the presence of disease or illness. Examples of energy medicine include magnet therapy, healing touch, and Reiki. Manipulative and body-based practices include massage, spinal manipulation, and reflexology. These modalities focus on the structure of the body including bones, joints, soft tissue, and circulatory systems. Mind-body medicine uses the energy of the mind to affect bodily functions and alleviate unwanted symptoms. Examples of this modality include meditation, yoga, tai chi, prayer, placebo effect, imagery, and creative outlets such as writing, poetry, music, and art.
Complementary and Alternative Medicine (CAM)Usage
According to the most recent National Health Interview Survey, 38% of adults are using some form of CAM. CAM use is greatest among women and those with higher educational and socioeconomic backgrounds. As seen in the figure above, CAM use is over 40% in the 50-69 year old population, 32% in those between 70-84 years old, and 24% in those aged 85 and above.
Barnes PM, Bloom B, Nahin R. CDC National Health Statistics Report #12. Complementary and Alternative Medicine Use Among Adults and Children: United States, 2007. December 2008.
Nonvitamin, nonmineral natural products are the most commonly used CAM modalities in the 2007 study. The most popular natural products were fish oil/omega 3, glucosamine, echinacea, flaxseed, ginseng, ginkgo, chondroitin, garlic, and coenzyme Q-10. People reported using CAM for a variety of conditions and diseases including musculoskeletal problems (back, neck, and joint pain), arthritis, anxiety, cholesterol, head and chest colds, headaches, and insomnia. Note: Notice the differences in the most popular natural products between the 2002 and 2007 study. Herbal use is highly influenced by the media and results of scientific studies. It is important to monitor media coverage of herbal supplements in order to be prepared to answer questions for clients regarding safety and effectiveness.
Regulatory IssuesDietary Supplements

Dietary supplements Vitamins Minerals Enzymes Amino acids Herbs Other botanicals Other dietary substances that increase total dietary intake
What exactly is a dietary supplement? The term dietary supplement is used to distinguish between prescription or over-thecounter (OTC) medications, and supplements that are used to promote health or enhance certain functions of the body. The definition of dietary supplements is rather broad and includes substances such as vitamins and minerals, herbs, enzymes, and any other dietary substance that increases the total dietary intake. Examples of dietary supplements include: vitamin C, selenium, papain, L-arginine, echinacea, yew bark, and royal jelly. Interestingly, homeopathic remedies are not considered dietary supplements. As discussed earlier, they are usually classified as nonprescription or over-the-counter medications and fall under the regulations of the Food, Drug and Cosmetic Act of 1938.
Regulatory IssuesDietary Supplement and Health Education Act (DSHEA)

Dietary Supplement and Health Education Act (DSHEA) Passed in 1994 Definition of dietary supplements Minimal labeling requirements Manufacturer is responsible for controlling quality and safety Standardized labels should include: Statement of identity Net quantity Structure/function claim Directions Supplement Facts panel Other ingredients Manufacturer name and address
Originally, vitamins and minerals were not classified as drugs in the Food, Drug, and Cosmetic Act of 1976. In the early 1990s consumers were concerned that the Food and Drug Administration (FDA) would tighten control of dietary supplements and limit their availability. In response to this concern the Dietary Supplement and Health Education Act, commonly known as DSHEA (pronounced dee-shay) was passed in 1994. Under DSHEA, dietary supplements were classified as foods rather than medications and fall under the regulatory authority of the Center for Food Safety and Applied Nutrition (CFSAN). Contrary to what many consumers think, the Food and Drug Administration (FDA) does not regulate herbal products which fall under and can only be marketed as dietary supplements. DSHEA established the definition of dietary supplements and provides minimal labeling requirements for supplements. Manufacturers of dietary supplements do not need to submit evidence of safety and efficacy to the FDA. Rather, manufacturers are responsible for good manufacturing practices and ensuring that their products contain the listed ingredients. As a result of DSHEA, the burden of proof to demonstrate that a supplement is unsafe lies with the FDA. The Federal Trade Commission (FTC) is responsible for monitoring labeling and advertising claims for dietary supplements. This includes newspaper, magazine, mail, television, radio, and internet ads.
Regulatory IssuesStandardized Labels
Allowable claims for dietary supplements: Nutrient content Health Structure/function
DSHEA allows three types of claims for dietary supplements. Nutrient claims can be made for substances that have a recognized use and recommended daily value. One example would be, Product X is a good source of vitamin C. Health claims are based on a body of scientific evidence that supports a relationship between the supplement and a particular disease or health condition. Currently there are only 11 allowable health claims authorized by the FDA. Examples include the use of calcium for the prevention of osteoporosis and folic acid for the prevention of neural tube defects. Most statements found on the labels or advertising of dietary supplements fall under the category of structure/function claims. Manufacturers of dietary supplements may claim that the product affects the structure or function of the body. However, they may not claim the supplement is effective for the prevention or treatment of disease. For example, a claim that glucosamine helps maintain joint fluidity is allowable but the claim that it helps reduce osteoarthritis is unallowable. Other examples of allowable claims include: Fiber maintains bowel regularity and Antioxidants maintain cell integrity. All structure/function claims must also contain a disclaimer statement that the FDA has not evaluated the claim.
Regulatory IssuesQuality Control

Adulteration concerns Wrong ingredient Products do not contain ingredients in the listed amounts Contains unlisted dietary supplements Contains prescription medications Contamination Heavy metals Pesticides Biological Quality control issues are of particular concern for dietary supplements. Although the FDA was given authority to establish Good Manufacturing Practices (GMP) through DSHEA in 1994, the final rules were not published until 2007. The GMP include requirements for quality control in manufacturing, packing, and labeling but do not ensure that a product is safe or effective. Adulteration remains a serious concern especially for products manufactured outside of the United States. Of particular concern are products advertised to enhance sexual function which often contain phosphodiesterase inhibitors or their analogs. One of many recent examples is the product Rose 4 Her which was recalled by the FDA because it contains thiomethisosildenafil, an analog of sildenafil. Drug-masking claims are also commonly found in weight loss products that include sibutramine or anti-aging products that contain growth hormones. Contamination is also a growing concern and may be either intentional or as a byproduct of growing, harvesting, or processing the product. Examples include lead contamination in some zinc lozenges, arsenic in a combination herbal product, or high levels of pesticide in an herbal concoction.
Dietary Supplement Verification Program Administered by the United States Pharmacopeia (USP) Verifies product was manufactured under good manufacturing practices (GMP) Verifies the ingredients listed on the label are in the declared amounts and strengths ConsumerLab.com Private company Products evaluated for quality, purity, and identity of listed ingredients and strengths American Herbal Products Association National trade association Issues recommendations for industry-wide self regulation Publishes Herbs of Commerce There are several ways for healthcare professionals to help patients identify quality dietary supplements. The Dietary Supplement Verification Program (DSVP) is administered by the United States Pharmacopeia (USP) and serves several functions. Dietary supplement manufacturers can voluntarily submit their products for evaluation by the USP. Supplements are tested for accurate listing of the ingredients on the label in the declared amounts and strengths. The USP also looks at the conditions under which the supplements are produced to ensure they meet good manufacturing practice standards. If the supplement meets the USP standards, the manufacturer can include the DSVP seal on the label.
Similarly, ConsumerLab.com evaluates dietary supplements for quality issues such as purity, strength and identity of listed ingredients, and bioavailability. Products are either submitted by the manufacturer or purchased by ConsumerLab.com for evaluation. Reviews are conducted every 4-6 weeks and grouped by ingredient (i.e., weight loss/slimming supplements, magnesium supplements, or acai berry). Products that meet all the standards may display the ConsumerLab.com seal of approval. Subscriptions to the website can be obtained for a small fee. Note: Neither the DSVP or ConsumerLab.com evaluate the safety and efficacy of the dietary supplements they review. The American Herbal Products Association is a national trade association that issues recommendations for industry-wide self-regulation. They also publish the Herbs of Commerce which lists herbs according to their standard and Latin binomial names. Any herb listed in the Herbs of Commerce can be referred to by its standard name in labeling and advertising.
Regulatory IssuesSafety
MedWatch Report serious adverse events www.fda.gov/Saftey/MedWatch Dietary Supplement and Nonprescription Drug Consumer Protection Act of 2006 Requires manufacturers to provide contact information on product label Manufacturers must notify the FDA of any serious adverse event Identifying safety concerns with dietary supplements is difficult because few adverse events are reported to the FDA and the information obtained may be incomplete. Voluntary reports of serious adverse events can be reported via the MedWatch program (available on the FDA website). Additional information regarding adverse events may also be published in case reports in the scientific literature. In order to increase reporting of adverse events related to dietary supplements, Congress passed the Dietary Supplement and Nonprescription Drug Consumer Protection Act at the end of 2006. This act requires manufacturers or distributors to list their contact information on the product label to allow consumers easy access to report adverse events. The manufacturer must report any serious adverse event to the FDA within 15 days of receiving the report.
Counseling Points: Recommending a Product

What are your goals for taking this supplement? Promote health Prevent/treat disease Are you taking prescription or non-prescription medications for this same purpose? Are you allergic to any plant materials? Is this product for personal use or for someone else, such as a child or elderly person? Before making a recommendation for a dietary supplement, it is important to consider the patients goals of therapy. Traditionally, people turn to dietary supplements to promote health and general wellness. There is an increasing trend however to use supplements in the prevention and treatment of disease. This is especially true in times of economic adversity. The pharmacist has a unique opportunity to screen patients for appropriate use of dietary supplements and also refer them to traditional healthcare providers for diagnosis and treatment of medical conditions and diseases. The pharmacist should also evaluate prescription medications, over-the-counter medications as well as dietary supplements for duplication of therapy. Dietary supplements may have similar pharmacologic effects to some prescription medications and lead to toxic side effects if taken concurrently. It is also important to inquire about the patients allergies to medications as well as plant materials and food. For example, people with allergies to ragweed should avoid the use of Echinacea. Finally, the pharmacist should remind the patient that dietary supplements should not be shared with children, pregnant or breastfeeding women, or those with compromised immune systems. Each person who is considering the use of a dietary supplement should speak with a healthcare provider, such as a pharmacist, to determine the products safety, effectiveness, and potential side effects.
Counseling Points: Re-evaluating Use

Re-evaluate herbal use if you: See no effect after several months Need surgery/invasive procedures Have cancer Start chemotherapy Have a change in medical condition Start/discontinue other medications Become pregnant Breastfeed Once a patient starts using a dietary supplement, it is important to re-evaluate its safety and effectiveness on a regular basis. If the supplement is not providing a beneficial or therapeutic effect, it should be discontinued. Likewise, if unwanted side effects emerge or the condition worsens, the supplement should be discontinued. It is also important to note that some adverse effects may not be apparent to the patient and may require periodic laboratory tests (i.e., liver function tests, hemoglobin/hematocrit, or serum creatinine). Several of the commonly used dietary supplements affect platelet aggregation or clotting factors. Whenever a patient is scheduled for surgery or invasive procedures (such as a colonoscopy, tooth extraction, etc.), all dietary supplements should be reviewed to determine if they affect the patients risk of bleeding. Some supplements such as ginkgo should be stopped 10-14 days prior to surgery. There are some concerns about the use of dietary supplements by people who have cancer or are undergoing chemotherapy. Some supplements are purported to be immune stimulants and may counteract the therapeutic effects of chemotherapy. Similarly, studies on the use of antioxidants during chemotherapy have shown conflicting results. The use of any dietary supplement during chemotherapy should be discussed with the patients oncologist or an oncology pharmacist. Although most consultant pharmacists do not typically care for women who are pregnant or breastfeeding it is important to remind patients not to share dietary supplements with family members who may become pregnant or are breastfeeding.
Dietary SupplementsMost Common Uses
Cardiac Health Hyperlipidemia Fish oil* Garlic Soy Hypertension Garlic* Fish oil Peripheral arterial disease Ginkgo
Digestive Health Respiratory Health Allergic rhinitis Chamomile Common cold Echinacea* Constipation Flaxseed* Dyspepsia Chamomile Ginger Motion sickness Ginger* Cognitive & Mental Health Anxiety Kava* Valerian Cognitive function Fish oil Ginkgo Ginseng Dementia Ginkgo* Womens Health Eye Health Glaucoma Glucosamine Menopausal symptoms Ginseng Hot flashes Black cohosh* Red clover* Soy* Depression Fish oil SAMe* St. Johns wort* Insomnia Chamomile* Melatonin* Valerian* Vertigo Ginkgo
Bone & Joint Health Osteoarthritis Chondroitin* Glucosamine* SAMe Osteoporosis Soy Rheumatoid arthritis Fish oil
Dietary SupplementsMost Common Uses
Mens Health Benign prostatic hyperplasia Saw palmetto* Miscellaneous Fatigue Ginseng* Sexual dysfunction Ginseng
Listed above are some of the common uses of the dietary supplements that will be covered in this module. The supplements are arranged and will be discussed in terms of their primary use (indicated by an asterisk). We will look at the common uses, standardization, active components, mechanism of action, effectiveness, adverse effects, interactions, and dosing of each supplement.
Fish oil (omega-3 fatty acids)

Common uses Hypertension Hypertriglyceridemia Cardiovascular disease prevention Mental development (EPA/DHA) Rheumatoid arthritis Bipolar disorder Depression Standardization Eicosapentaenoic acid (EPA) Docosahexaenoic acid (DHA) Alpha-linolenic acid (ALA)plant derived Mechanism of action Anti-inflammatory Decrease platelet aggregation Vasodilation Decreases triglycerides Fish oil is commonly used for cardiovascular conditions such as hyperlipidemia, hypertriglyceridemia, and the prevention of coronary artery disease. It is also used for rheumatoid arthritis and some psychiatric conditions such as bipolar disorder and depression. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in infant formulas and baby foods to enhance mental development in young infants and children. Fish oil is found in large quantities in fatty fish such as herring, mackerel, salmon, sardines, and trout and to a lesser extent in shrimp, oysters, and scallops. Fish oil contains a high concentration of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Unfortunately, the human body cannot produce omega-3 fatty acids or convert omega-6 fatty acids, which are plentiful in the Western diet, into omega-3 fatty acids.

Alpha-linolenic acid (ALA) is the plant derived omega-3 precursor to DHA and EPA. It has some beneficial cardiac effects but may cause a slight increase in triglycerides. ALA does not have the same effect as EPA or DHA on cholesterol lowering. However, it may have some activity in breast cancer (trials ongoing). Fish oil has both anti-inflammatory and antithrombotic properties. It decreases the synthesis of thromboxane A2 which competes with arachidonic acid in the COX pathway. This leads to decreased platelet aggregation and decreased vasoconstriction. Fish oil also produces an increase in prostaglandins and decreases anti-inflammatory cytokines. The beneficial effects of fish oil are due to decreased very low density lipoprotein (VLDL) secretion, increased VLDL clearance and decreased triglyceride transport. The overall size of low density lipoprotein (LDL) particles may increase leading to elevated LDL levels. However, these larger LDL particles may not be as atherogenic due to increased buoyancy.

Effectiveness Hypertension: slight decrease (2-5mm mercury) Hyperlipidemia Decreases triglycerides (20-30%) Slightly increases LDL (5-10%) Mental development Infants: some increase in cognitive development Dementia: insufficient evidence Several trials have confirmed the antihypertensive effects of fish oil. The effects appear to be dose-dependent but usually do not exceed 2-5mm mercury. DHA may contribute a greater effect than EPA for this indication. The clinical effectiveness of this magnitude of decrease may or may not be significant for the patient. The most common use of fish oil is for hypertriglyceridemia. The commercial product Lovaza (formerly known as Omacor) is FDA approved for this indication in patients with triglyceride levels greater than 500mg/dl. Lovaza is standardized to 465mg EPA and 375mg DHA in each 1 gram capsule. Various dietary supplements are also available overthe-counter but may have different side effects (due to manufacturing processes) and varying concentrations of EPA and DHA. Overall, fish oil may decrease triglyceride levels by 20-30%. There is some concern however that fish oil will also increase LDL. It may be prudent to periodically monitor the patients lipid panel to detect any clinically significant changes. EPA and DHA are commonly added to infant formulas and some baby foods to increase cognitive development. It is believed that these omega-3 fatty acids aid in the development of neuronal and synaptic membranes. There is insufficient evidence however for the use of fish oil to prevent a decline in cognitive function or dementia in adults. Fish oil may have a beneficial effect when combined with conventional therapies for the symptoms of depression associated with bipolar disorder but has no effect on manic symptoms. Likewise, fish oil may enhance the effect of conventional antidepressants in patients with depression. The consumption of fish has been associated with decreased incidence of depression and suicide in some epidemiological studies.

Adverse effects Fishy burp or aftertaste Halitosis Heartburn Loose stool Interactions Antiplatelet agents or anticoagulants >3g can inhibit platelet aggregation Vitamin A toxicity Dosing Prevention American Heart Association: 2 servings/week World Health Organization: 0.3-0.5 grams daily Therapeutic 1-4 grams/day in a single or divided doses The most commonly reported adverse effects of fish oil are a fishy burp or aftertaste, halitosis, heartburn, and loose stool. Taking supplements with meals or starting with a low dose and slowly titrating up may decrease these side effects for some patients. Enteric coated fish products or storing them in the freezer may also help reduce these bothersome side effects. At very high doses, it is possible to develop severe diarrhea. In the 1980s there were reports of fish oil causing an increased need for insulin in diabetic patients. Subsequent studies have found no correlation between fish oil and increased fasting blood glucose, hemoglobin A1c, or insulin needs. The earlier findings may be due to normal progression of the disease, changes in dietary habits, or possible weight gain.

Recently there has been concern about the level of mercury contamination in fatty fish. Many of the fish oil products currently on the market have been tested and have very little to undetectable levels of mercury. It is prudent however for healthcare professionals to be aware of the common signs and symptoms of toxicity from contaminants found in fish. The signs of mercury poisoning include tremor, numbness and tingling, difficulty concentrating, and vision problems. Polychlorinated biphenyls (PCBs) are carcinogenic and can cause memory loss. Dioxin is present in the fish feed of farmraised salmon and has carcinogenic, immunosuppressive, and toxic central nervous system effects. It is recommended to limit the servings of farm-raised salmon to less than 10 times/month to avoid dioxin contamination. Fish oil may increase bleeding time, especially when combined with other antiplatelet agents or anticoagulants. Some clinical studies have found that doses greater than 3 grams can inhibit platelet aggregation. However, other evidence suggests fish oil in doses up to 6 grams daily does not significantly affect bleeding time. Overall, fish oil has less effect on bleeding than a daily dose of aspirin. Advise patients to use high-dose fish oil cautiously if they take other antiplatelet or anticoagulant drugs and monitor for signs of excessive bleeding or bruising. Some fish oil preparations derived from fish liver rather than fish meat contain large concentrations of vitamin A and vitamin D. If these preparations are used long-term or in large doses, there is a risk of vitamin A and D toxicity. The American Heart Association recommends eating fish, preferably fatty fish, at least twice weekly. Various dietary authorities also recommend consuming alpha-linolenic acid, from sources such as tofu, soybeans, walnuts, flaxseed oil, or canola oil. The World Health Organization provides a more specific recommendation of consuming 0.3-0.5 grams of EPA and DHA daily and 0.8-1.1 grams of daily alpha-linolenic acid. Dietary supplements containing 1-4 grams/day are recommended to achieve antihypertensive effects and lower triglyceride levels. Note: Consider the caloric impact if fish oil is used on a long-term basis. Fish oil capsules usually contain 500mg of omega-3 fatty acids in 1 gram of oil which would supply 13.5kcal per capsule.
Garlic
Common uses Hypertension Hypercholesterolemia Colorectal cancer Tick bites Standardization Varied or absent 1.5% alliin content (clinical studies) Active components Allicin Ajoene S-allyl-L-cystein Other organic sulfur compounds
Mechanism of action Inhibits platelet aggregation Increases fibrinolysis Induces vasodilation and relaxation of smooth muscle Garlic (Allium sativum) is commonly used as a food as well as a supplement to treat hypertension and hypercholesterolemia. Some preliminary data suggests that garlic may be beneficial in preventing colorectal and gastric cancers, tinea pedis, tinea corporis, tinea cruris, and tick bites. Historically, garlic has also been used for benign prostatic hyperplasia, breast cancer, diabetes, H. pylori infections, peripheral arterial disease, and prostate cancer.
Garlic
The amino acid alliin (pronounced allen) is present in the intact cells of garlic bulbs. Alliin is an odorless, sulfur-containing amino acid that has no clinical activity. When garlic bulbs are crushed or chewed, alliin comes into contact with the enzyme allinase and produces allicin (pronounced allisun). Allicin is the odoriferous compound that gives garlic its characteristic smell. Allicin is unstable and is quickly converted to compounds such as ajoene and other sulfur-containing chemicals. The therapeutic effects of garlic are attributed to allicin, ajoene, and other organic sulfur-containing components such as s-allyl-Lcysteine. S-allyl-L-cysteine may inhibit hepatic cholesterol synthesis which is the purported mechanism for the cholesterol lowering effects of garlic. Garlic may also inhibit platelet aggregation and increase fibrinolysis. It appears that raw garlic has stronger antiplatelet effects compared to cooked garlic, but crushing the bulb before cooking may retain most of the antiplatelet effects. The mechanism responsible for the blood pressure lowering effects of garlic may be the stimulation of endotheliumderived relaxation factor (EDRF) or nitric oxide. This leads to vasodilation and the relaxation of smooth muscle.
Garlic
Effectiveness Hyperlipidemia Early studies showed reduction of TC, LDL, triglycerides More recent studies showed no cholesterol effect Hypertension Reduces systolic blood pressure up to 8% Reduces diastolic blood pressure up to 7% Tick bites
Early studies, mostly done in the 1990s, showed that garlic supplements modestly, but consistently, reduced total cholesterol, LDL cholesterol, and triglycerides. The problem is that these studies were generally low quality. They were often small, flawed, and inconsistently designed. More recent research has been consistent in the opposite direction. These studies show that a variety of garlic preparations do not significantly reduce total cholesterol, LDL cholesterol, or other lipid concentrations. More promising research focuses on the use of garlic to reduce blood pressure. Garlic has shown some benefit in the treatment of hypertension. Systolic blood pressure may be reduced by 8% and diastolic pressure by 7% in normotensive and hypertensive patients. Studies were performed with powdered garlic supplements and aged garlic supplements. Interestingly, several small studies have shown a reduction in the number of tick bites compared to controls when large doses of garlic are consumed on a regular basis.
Garlic
Adverse effects Breath and body odor Heartburn Flatulence Nausea/vomiting Contact dermatitis Spontaneous bleeding (rare) Interactions Warfarin Antiplatelet agents Protease inhibitors 3A4 substrates Dosing 600-1200mg extract in divided doses 4g fresh garlic (1 clove)
The most common adverse effects associated with garlic are breath and body odor, heartburn, nausea, vomiting, diarrhea, and flatulence. Contact dermatitis has also been reported with the use of topical garlic preparations. The most serious side effects are bleeding due to garlics antiplatelet activity. Bleeding has been reported with the use of dietary garlic as well as garlic supplements. It is important to counsel patients to stop garlic supplements at least 5 days prior to any major elective surgery.
Garlic
Garlic may prolong bleeding time when combined with other antithrombotic or antiplatelet medications. Garlic supplements seem to have a stronger effect on platelet inhibition than fresh garlic. This may be due to the components and relative strengths of the active ingredients in each type of supplement. Garlic also substantially decreases the plasma concentrations of isoniazid, saquinavir, and the non-nucleoside reverse transciptase inhibitors. Effects vary with garlic preparation, but it is recommended that patients on these medications avoid the use of garlic. Garlic may induce CYP 3A4 depending on the presence of allicin and other components in the supplement. Caution is advised when patients start or stop taking medications metabolized via CYP 3A4. Such medications include calcium channel blockers, some chemotherapy agents, antifungals, glucocorticoids, fentanyl, losartan, and fexofenadine. Dosing for clinical effect is usually 600-1200mg in divided doses or 4g of fresh garlic (approximately one clove). It is important to note that active constituents vary widely in different garlic supplements. Some odorless preparations may contain no active ingredients.
Flaxseed
Common uses Constipation Diabetes Hot flashes Hypercholesterolemia Active components Soluble fiber Alpha-linolenic acid Mechanism of action Soluble fiber acts as a bulk forming laxative Fiber content increases fecal excretion of bile salts, increasing bile acid synthesis Lignan (phytoestrogen) content has weak estrogenic and antiestrogenic effects Flaxseed (Linum usitatissimum) is both a food and dietary supplement commonly used for constipation, cardiovascular disease, and hypercholesterolemia. Other uses of flaxseed include diabetes, menopausal symptoms, and the prevention of various forms of cancer. The active components of flaxseed are the soluble fiber and fatty acid content which includes over 50% alpha-linolenic acid (ALA). The soluble fiber in the seed coat acts as a bulk forming laxative. Flaxseed oil is one of the richest sources of the omega-3 fatty acid, alpha-linolenic acid. Unfortunately, the body is only able to convert very small amounts of ALA into the more unsaturated fatty acids eicosapentaenoic (EPA) and docosahexaenoic acids (DHA). It is the EPA and DHA content of fish oil that is responsible for decreasing serum triglycerides. In contrast, it is the fiber content of flaxseed that is most likely responsible for decreasing total cholesterol synthesis. The high fiber content increases fecal excretion of bile salts thus increasing bile acid synthesis and reducing overall cholesterol synthesis. In addition, flaxseed contains lignans which are phytoestrogens with weak estrogenic and antiestrogenic properties. It is the phytoestrogen component that is being studied for the treatment and prevention of menopausal symptoms such as hot flashes.
Flaxseed
Effectiveness Constipation: No clinical research Diabetes: Based on one study, a specific lignan extract reduced A1c but had no effect on fasting blood sugar Hot flashes: 40 grams crushed flaxseed daily reduced hot flashes by 35% and night sweats by 44%; 25 grams in baked goods had no effect Hypercholesterolemia: 40 to 50 grams may reduce total cholesterol by 5% to 9% and LDL cholesterol by 8% to 18% There are no clinical studies on the use of flaxseed for constipation. Due to the bulk forming properties of fiber, it is important to take flaxseed with adequate amounts of liquid to prevent bowel obstruction. One study found that a specific 600 mg lignan extract taken three times daily, significantly reduced hemoglobin A1c levels but had no effect on fasting blood sugar or circulating insulin levels. Due to the reduced fatty acid content of the extract there was no beneficial effect on cholesterol levels. Caution patients that flaxseed should not replace other pharmacologic and non-pharmacologic interventions until more clinical studies are conducted. Data on the effectiveness of flaxseed for menopausal symptoms is mixed. In one study, women with mild baseline symptoms showed a 35% reduction in hot flashes and 44% decrease in night sweats after taking 40 grams of crushed flaxseed daily. Other studies have shown flaxseed to have comparable effectiveness to hormone therapy while others showed no difference from placebo (wheat germ). Studies with lower flaxseed content in the form of baked goods showed no improvement in hot flashes or quality of life. Various forms of flaxseed have shown benefit in reducing total cholesterol and low density lipoprotein (LDL) in people with normal cholesterol as well as hypercholesterolemia. The most promising studies used 40-50 grams of crushed or baked flaxseed and saw a reduction of 5-9% in LDL and 8-18% in total cholesterol. Natural flaxseed has no effect on high density lipoprotein (HDL) or triglycerides, however, defatted flaxseed extract may slightly increase triglycerides secondary to decreased omega-3 fatty acid content.
Flaxseed
Adverse effects Bloating Flatulence Abdominal pain Diarrhea Bleeding (rare) Cautions Take with fluid to prevent bowel obstruction Raw or unripe flaxseed may contain cyanogenic glycosides 40 grams of flaxseed contains 16 grams of fat and ~200 calorie Dosing Diabetes: 600 mg lignan extract three times daily (provides 320mg lignans) Hot flashes: 40 grams crushed flaxseed daily Hypercholesterolemia: baked goods with 40-50 grams flaxseed daily
Flaxseed is generally very well tolerated. Some patients may experience bloating, flatulence, abdominal pain, or diarrhea due to the fiber content of flaxseed. Caution patients to take flaxseed with plenty of fluids to prevent worsening of constipation or in very rare cases, bowel obstruction. Flaxseed may inhibit platelet aggregation and increase the risk of bleeding when taken in large doses (usually greater than 50 grams per day). Caution patients who are taking antiplatelet or anticoagulant medications about the potential interaction with flaxseed. Raw or unripe flaxseed may contain cyanogenic glycosides. These compounds are undetectable when flaxseed is consumed in baked goods. The potential for human harm is unknown and unlikely at doses less than 50 grams per day. Caution patients to use flaxseed in place of other dietary fats rather than in addition to them because 40 grams of flaxseed contain 16 grams of fat and over 200 calories. However, flaxseed is a healthy alternative to other fats and very safe. Dosing for flaxseed is generally 40-50 grams of crushed or baked flaxseed daily. The studies done in diabetic patients utilized a specific lignan extract that provided 320 lignans daily.
Ginger
Common uses Motion sickness Dyspepsia Loss of appetite Rheumatoid arthritis Active components Gingerol Gingerdione Shogaol Galanolactone Volatile oils (various) Mechanism of action May affect serotonin receptors in the digestive tract May inhibit cyclooxygenase and lipoxygenase
Ginger (Zingiber officinale) is commonly used for motion sickness, loss of appetite, and some anti-inflammatory conditions such as rheumatoid arthritis. It is also used for morning sickness in pregnant women and in some settings for chemotherapy-induced nausea and vomiting. The active components of ginger include gingerol, gingerdione, shogaol, galanolactone and other volatile oils. The amount of each component varies depending on the preparation of the ginger (i.e. dried root, fresh, powdered). The exact mechanism of action of ginger is unknown at this time. It is thought that ginger may affect the 5HT3 serotonin receptors in the digestive tract in a manner similar to other antiemetics. Another proposed mechanism is the inhibition of the cyclooxygenase and lipoxygenase pathways. This mechanism may be responsible for the purported antiinflammatory effects of ginger.
Ginger
Effectiveness: unknown Adverse effects Bloating Flatulence Heartburn Diarrhea Interactions Anticoagulants Antiplatelet agents Dosing 1-4 grams daily There is a lack of reliable evidence to assess the effectiveness of ginger for most indications. There are several studies citing the benefit of ginger for morning sickness however, the safety of medicinal doses of ginger in pregnancy is controversial. The studies for chemotherapy- or radiation-induced nausea and vomiting are inconclusive. Ginger is relatively well tolerated. The most common side effects are bloating, flatulence, heartburn and diarrhea when consumed in large doses. There is a theoretical interaction between ginger and anticoagulants or antiplatelet medications. Ginger can increase bleeding time by inhibiting thromboxane and decreasing platelet aggregation. Counsel patient to avoid this combination and inform healthcare worker prior to any surgical procedures. The recommended dose of ginger is 1-4 grams of dried root per day.
Echinacea
Common uses Colds Respiratory infections Standardization: none Mechanism of action Stimulation of non-specific immune system Anti-inflammatory effects
Echinacea, also known as the purple coneflower, is one of the most well-known and popular dietary supplements on the market today. It is commonly used for the treatment and prevention of the common cold and other respiratory infections. Three species of echinacea are commonly used in commercial preparations and include E. purpurea, E. augustfolia, and E. pallida. The roots and aboveground parts including the flowers, leaves, and stems all contain active constituents. Unfortunately, there is no standardization for echinacea preparations. Commercial preparations may contain more than one species, different parts of the plant, or be prepared by different methods such as drying, pressing, or alcoholic extraction. The exact mechanism of action of echinacea is unknown. In vitro studies demonstrate that several components of echinacea stimulate the non-specific immune system, however, no effect is seen in the immune system of healthy volunteers. There has been recent speculation that the effects of echinacea are due to possible anti-inflammatory effects rather than immune effects.
Echinacea
Effectiveness Likely safe but ineffective May reduce symptom duration/severity by 10-30%
Echinacea may decrease the severity and duration of the common cold when taken at the first sign of symptoms. A recent meta-analysis found that echinacea decreased the incidence of developing a cold by 58% and the duration by 1.4 days. The clinical significance of this finding is unknown. There is no evidence that the chronic use of echinacea will prevent the development of the common cold. The bottom line in terms of effectiveness is that echinacea is likely safe but clinically ineffective. The best evidence appears to be for preparations of the Echinacea purpurea species. If a patient decides to try echinacea, suggest preparations using this species. Adverse effects GI effects Tingling sensation on tongue Headache Allergic reactions Contraindications Ragweed allergy History of asthma, atopy, allergic rhinitis Severe autoimmune disease
Interactions Inhibits 1A2 Inhibits intestinal 3A4 Induces hepatic 3A4 Dosing Initiate therapy at the onset of cold symptoms Continue therapy for 10-14 days
Echinacea
Adverse effects of echinacea are very mild and include complaints of mild gastrointestinal discomfort, a tingling sensation of the tongue, and headache. Patients with allergies to the ragweed family (Asteraceae) should avoid the use of echinacea. Allergic reactions have also been reported in patients with a history of asthma, atopy (a genetic tendency to develop the classic allergic diseases of atopic dermatitis, allergic rhinitis, and asthma), and allergic rhinitis. Patients with these conditions should avoid echinacea or use with extreme caution. Several reference sources list severe autoimmune disease as a contraindication to the use of echinacea. This is a theoretical concern based on the presumption that echinacea may stimulate the immune system. No interactions of this type have been reported but patients with these conditions should use echinacea with caution. No drug interactions have been reported with the use of echinacea. In vitro studies have shown that echinacea inhibits CYP 1A2 however, the clinical significance is unknown. Although echinacea inhibits intestinal CYP 3A4 it also induces hepatic CYP 3A4 and the effects may cancel each other. Drug interactions are a theoretical concern at this point but it would be prudent to monitor patients who use echinacea on a routine basis. Due to the plethora of products available in various dosage forms, there is no standard recommendation for dosing. Refer to the product label or a reputable drug information source for dosing according to preparation and formulation of each product. It is generally recommended to initiate therapy at the onset of cold symptoms and continue therapy for 10-14 days. Echinacea should not be used on a routine basis for the prevention of colds.
Chondroitin
Common uses Osteoarthritis Osteoporosis Ischemic heart disease Mechanism of action Glycosaminoglycans (GAGs) act as substrates for the joint matrix structure of cartilage Possible antiatherogenic properties (animal studies) Effectiveness Modest to possibly insignificant reduction in pain from osteoarthritis of the knee Chondroitin sulfate is often used in combination with other supplements such as glucosamine or manganese to treat osteoarthritis. There are also preliminary studies on the use of chondroitin for the treatment and prevention of ischemic heart disease and osteoporosis. Chondroitin is composed of large glycosaminoglycans (GAGs) that act as substrates for the joint matrix structure of cartilage and is found in most cartilaginous tissues. Chondroitin may also have some protective effects via inhibiting the enzymes responsible for the degradation of cartilage. The exact mechanism of action of chondroitin is unknown at this time. The results of many early studies on the use of chondroitin for osteoarthritis of the knee and hip looked promising. Patients showed improvement in pain scales and global functioning after several weeks of treatment. A particular combination of chondroitin, glucosamine, and manganese also showed improvement in both subjective and objective pain scores in patients with osteoarthritis of the knee. Subsequent studies however, show little if any improvement in pain scores. One large-scale study found no overall improvement in pain for patients taking chondroitin alone or in combination with glucosamine. However, they did find modest improvement in pain among a subset of patients with moderate to severe osteoarthritis of the knee (placebo rate >60%).
Chondroitin
Adverse effects Heartburn Nausea Cautions Produced from bovine cartilagepossible contamination Potential anticoagulant effect Ensure manganese content does not exceed tolerable upper limit of 11mg per day Dosing 200-400mg two or three times daily Single daily dose of 1000-1200mg Intermittent dosing: 3 months of treatment, 3 months of no treatment, then another 3 months of treatment Chondroitin is generally very well tolerated. The most common complaint is either heartburn or nausea. Diarrhea, constipation, and alopecia have been reported in clinical trials of chondroitin and glucosamine. It is unclear which of the supplements is responsible for these side effects. There is potential for chondroitin to be contaminated with diseased animal material because it is produced from bovine trachea cartilage. To date, there are no reports of bovine spongiform encephalopathy (BSE) or other animal transmitted disease related to chondroitin. Chondroitin is a small component of a heparinoid and may theoretically have anticoagulant effects. There are case reports of increased INRs in patients taking warfarin together with glucosamine and chondroitin combination products. Glucosamine is also a small component of heparin and may have anticoagulant or antiplatelet effects. Caution patients using combination chondroitin products to check the total daily manganese content. Manganese should not exceed the tolerable upper limit of 11mg per day.
Glucosamine
Common use Osteoarthritis Joint pain Glaucoma Mechanism of action Stimulates metabolism of chondrocytes Possible disease-modifying effect Effectiveness Improves pain and functionality in patients with osteoarthritis of the knee Glucosamine, or 2-amino-2-deoxyglucose, is an amino sugar and a component of cartilage proteoglycans. Commercial products contain glucosamine as either a hydrochloride or sulfate salt. Debate exists regarding the relative effectiveness of the different salt forms. Glucosamine can be derived from the exoskeletons of shrimp, lobster, and crabs or made synthetically. Glucosamine is commonly used for osteoarthritis, joint pain, and glaucoma. Glucosamine is involved with the metabolism of chondrocytes and synovial cells. Some research has shown that glucosamine may have a disease-modifying effect for osteoarthritis. In vitro studies have demonstrated that glucosamine inhibits protein glycosylation and the formation of inflammatory cytokines which are also involved with cartilage breakdown. Although glucosamine does not directly inhibit the cyclooxygenase pathway, it may inhibit the gene expression and protein synthesis of cyclooxygenase-2. There is conflicting evidence regarding the effectiveness of glucosamine. The most positive results for glucosamine are when it is used to treat osteoarthritis of the knee. Glucosamine can reduce pain and improve functionality but does not relieve acute flare-ups. There is little evidence supporting the use of glucosamine for osteoarthritis of other joints such as the hip or lower back.
Glucosamine
Adverse effects Mild GI complaints Altered glucose metabolism Interactions Warfarin: increased INR Shellfish allergy Dosing Sulfate vs. HCl salt Sulfate moiety may be active ingredient Glucosamine 500mg TID or 1500mg QD Glucosamine is generally well tolerated with the most common side effects being mild gastrointestinal complaints of nausea, diarrhea, and constipation. There is some concern that glucosamine may alter glucose metabolism by inhibiting beta cells in the pancreas. Research in human subjects however show no effect on the pharmacokinetics of glucose metabolism. Advise patients with diabetes or impaired glucose tolerance to monitor their blood sugars periodically to assess for any changes. There are several case reports of increased INRs in patient taking warfarin and glucosamine concomitantly. The increased INR can be seen with conventional doses of 1500mg QD as well as megadoses of glucosamine. Counsel patients on warfarin to avoid the use of glucosamine or use with extreme caution and monitor INRs whenever they increase or decrease the glucosamine dose.
Glucosamine
There is also concern of hypersensitivity reactions to glucosamine in patients with shellfish allergies, however there are no documented reports. Allergic reactions in people with shellfish allergy are caused by an IgE response to the meat of shellfish, not to antigens in the shell. Patients with severe shellfish allergies should avoid use of glucosamine as a precautionary measure or use synthetically produced glucosamine. There is debate regarding the efficacy of the various salt forms of glucosamine. Most clinical trials have been done with glucosamine sulfate but the most common form on the market is glucosamine hydrochloride. In one head to head trial there was no difference between the two salt forms in terms of pain relieve over a 4 week period. Some researchers have noted that the length of this trial was too short, there was no placebo group, and the dosing was three times daily rather than the once daily administration which has shown benefit for the sulfate form. Other researchers have also postulated that the sulfate moiety in glucosamine sulfate might be responsible for its effect on osteoarthritis. Dosing of the hydrochloride form is usually 500mg three times daily and the sulfate form is dosed at 1500mg daily. Advise patients that it may take 4-8 weeks for the pain relief to reach maximal effect.
Kava
Common uses Anxiety Stress Effectiveness Possibly similar to benzodiazepines Studies contained highly concentrated extracts Adverse effects GI upset Dizziness Headache Hepatotoxicity Relatively normal doses, short term (1-3 months) Banned in several countries Kava (Piper methysticum), also known as kava kava, is native to the South Pacific islands where it is commonly used for ceremonial purposes. It was discovered by Captain Cook who named the plant intoxicating pepper and introduced it to the rest of the world. Today, kava is used to relieve anxiety and stress or ease the symptoms of benzodiazepine withdrawal. Studies regarding the effectiveness of kava are conflicting. Some studies show efficacy similar to benzodiazepines but contained standardized extracts that were double the strength of most commercial products. The reason for including kava in this module however, is related to its potentially fatal side effects.The use of kava for as short as one to three months has resulted in the need for liver transplants, and even death. Kava has been banned from the market in Switzerland, Germany, and Canada; while several other countries are considering similar action. Kava is used for ceremonial purposes on a regular basis in South Pacific islands however without incident of hepatotoxicity. Due to the potentially fatal adverse effects, do not recommend the use of kava on a routine basis. If patients continue to use kava, recommend routine liver function tests to screen for hepatotoxicity.
Ginkgo
Common uses Dementia Cognitive function Peripheral arterial disease (PAD) Intermittent claudication Raynauds syndrome Vertigo Standardization Flavonoid glycosides: 25-26% Terpenoids: 6% Mechanism of action Antioxidant activity reduces oxidative damage to tissues Anti-inflammatory properties Inhibits platelet activating factor (PAF) Increases microcirculatory blood flow Ginkgo (Ginkgo biloba) is the oldest living species of tree in the world and individual trees may live for more than a thousand years. Traditionally the fruit of the plant was used for medicinal purposes but now extracts are prepared from the leaves. Ginkgo is most commonly used for dementia and improving cognitive function. It has been studied for various forms of dementia including vascular dementia, Alzheimers disease, and mixed dementia. Several studies have also examined the role of ginkgo in improving circulatory flow for primary or secondary prevention of stroke and its complications. The cerebrovascular effects of ginkgo may be beneficial for treating patients with vertigo or tinnitus. In addition, ginkgo is used to improve microcirculatory flow in conditions such as peripheral arterial disease, intermittent claudication, and Raynauds syndrome.
Ginkgo
Ginkgo may have some beneficial effect in preventing the progression of diabetic retinopathy, however, it may affect blood glucose control. Ginkgo has little effect on blood glucose in diabetic patients who are diet controlled, but it may increase insulin metabolism in patients who require oral antidiabetic medications. Ginkgo extracts are usually prepared from the leaves of the plant and may be standardized to 25-26% flavonoid glycosides and 6% terpenoids. Fresh seeds and extracts from seeds should be avoided or used with extreme caution because they contain high concentrations of ginkgotoxin (see adverse events). The mechanism of action of ginkgo is poorly understood but may be related to its antioxidant effects. Reduction of oxidative stress in cerebrovascular tissues may improve cognitive function or slow the progression of dementia. In addition, ginkgo possesses anti-inflammatory activity and affects microcirculatory flow by decreasing blood viscosity and modulating vascular smooth muscle. Ginkgo competitively inhibits platelet activating factor (PAF) and the formation of platelet thromboxane A2 and thromboxane B2 thereby inhibiting platelet aggregation. Effectiveness Ginkgo Evaluation of Memory (GEM) study Randomized, double-blind, placebo-controlled trial Large, multicenter study (3,000 participants) Enrollment 75 years or older (mean age 79) No cognitive impairment Mild cognitive impairment
Ginkgo
Exclusion Criteria Cholinergic enhancer use Bleeding disorders Neurodegenerative disease Use of ginkgo prior to study Primary outcome Incidence of all-cause dementia Data regarding the effectiveness of ginkgo is conflicting. In some earlier studies it appeared that ginkgo may have mild to moderate effectiveness with regards to improving cognitive function. There is also some evidence suggesting that 120-240 mg daily of a standardized ginkgo extract can modestly improve cognitive function in patients with Alzheimer's-related and other forms of dementia. However, another study in patients with more advanced Alzheimers disease and neuropsychiatric complications showed no benefit. In order to resolve this conflict the Ginkgo Evaluation of Memory (GEM) study was launched in 2000. GEM The GEM study enrolled more than 3,000 participants age 75 or older with mild or no cognitive impairment. The mean age was 79 years and 46% of the participants were women. Study participants were followed on average for 6.1 years with a maximum of 7 years. They were given 120mg capsules of ginkgo biloba extract twice daily or matching placebo. The study was a multicenter, randomized, double-blind trial conducted in the United States. The primary outcome of the study was all cause dementia as determined by a panel of experts. During the course of the study 246 people in the placebo group and 277 in the ginkgo group were diagnosed with dementia. The hazard ratio (HR) for ginkgo compared to placebo for all-cause dementia was 1.12 (95% confidence interval [CI], 0.94-1.22; p=.21) Therefore, ginkgo showed no benefit in reducing the incidence of all-cause dementia. Ginkgo also had no effect on the progression of dementia in patients with mild cognitive impairment (HR=1.13; 95% CI, 0.85-1.50; p=.39). The ginkgo was well tolerated and there was no increased risk of bleeding in the study group.
Ginkgo
Questions remain regarding the use of ginkgo to prevent dementia in younger patients as well as the active treatment of Alzheimers disease with ginkgo. Some researchers believe ginkgo may provide an improvement in cognition that equates to about a six-month delay in progression of the disease. Adverse effects GI complaints Allergic reactions Bleeding Interactions Antiplatelet agents or anticoagulants Medications that lower the seizure threshold Dosing 40-80mg TID May need higher doses for claudication The adverse effects related to ginkgo are relatively mild. The most commonly reported complaint is mild gastrointestinal upset which can be minimized by taking the extract with food. Allergic reactions to ginkgolic acid have been reported in the literature. This component is found in crude extracts of ginkgo leaves and may have mutagenic and carcinogenic properties. Standardized extracts should contain no greater than 5ppm of ginkgolic acids. Ginkgotoxin is found in ginkgo seeds and can cause seizures, paralysis and even death when taken in very high doses. Avoid eating or consuming extracts prepared from raw ginkgo seeds. Boiling the seeds may reduce the level of ginkgotoxin to safe levels, however this practice is not recommended. Most commercial formulations are prepared from leaves or leaf extracts which contain little or no ginkgotoxin. Evidence linking ginkgo to seizures is inconclusive, however, it is prudent to suggest caution to those with seizure disorders or patients taking other medications that may lower the seizure threshold.
Ginkgo
The greatest concern with ginkgo extracts is the potential for bleeding, especially when combined with other anticoagulant or antiplatelet medications. Although the INR is not affected in patients who are only taking ginkgo and no other anticoagulants, spontaneous bleeding has been reported in very rare cases. Bleeding has also been reported in patients who are concomitantly taking non-steroidal anti-inflammatory medications. Monitor the INR and signs and symptoms of bleeding closely for any patients who are taking warfarin and ginkgo. Ginkgo should be discontinued 7-10 days (absolute minimum of 36 hours) before any surgical procedure. Dosing is based on standardized extracts and is typically started at 40mg TID and increased to 80mg TID as tolerated. It is important to remind patients that it may take 6-8 weeks to see any improvement in cognitive function. Higher doses may be needed for treating intermittent claudication. Note: In vitro studies provide conflicting data on the effect of ginkgo on the CYP450 system. There are no clinically significant interactions between ginkgo and the CYP450 system.
SAMe
Common uses Depression Osteoarthritis Fibromyalgia Mechanism of action Influences neuronal membrane fluidity Increases serotonin turnover Increases norepinephrine and dopamine levels
SAMe (s-adenosyl-L-methionine) is a naturally occurring amino acid found in the body and in protein food sources. It is commonly used for the treatment of depression, osteoarthritis, and fibromyalgia. Other uses include intrahepatic cholestatis, chronic fatigue syndrome, and attention deficit hyperactivity disorder. SAMe is involved in many biochemical processes in the body. It is involved in the synthesis or activation of various hormones, proteins, and medications. SAMe synthesis is also related to folate and vitamin B12 metabolism. When patients are folate or vitamin B12 deficient, there are lower serum concentrations of SAMe. The clinical significance of this association however is unknown at this point. The exact mechanism of action for SAMe is unknown. It is thought that SAMe influences neuronal membrane fluidity thus increasing signal transduction. SAMe does increase serotonin turnover and increase both norepinephrine and dopamine levels which may contribute to its antidepressant effects. SAMe also has some anti-inflammatory and analgesic effects.
SAMe
Effectiveness Depression IV: similar to tricyclic antidepressants PO: superior to placebo; larger studies needed Osteoarthritis: superior to placebo; similar to NSAIDs (including celecoxib) Fibromyalgia: superior to placebo (oral)
Intravenous administration of SAMe was found to be superior to placebo in the treatment of major depression in several small trials of short duration. SAMe may also be equally as effective as tricyclic antidepressants when used intravenously for up to 30-days. Of note, the onset of symptom alleviation was after 1-2 weeks. Short-term administration of intravenous SAMe was also studied in combination with oral tricyclic antidepressants to shorten the onset of action. Trials of oral SAMe show some benefit for the treatment of major depression but are limited by study design, small sample sizes, and poor methodology. Several clinical trials have shown that oral SAMe is superior to placebo and similar in efficacy to the non-steroidal antiinflammatory drugs (NSAIDs) including the cyclooxygenase (COX) II selective medication celecoxib. SAMe showed improvements in pain scores as well as functional limitations in most of the studies. Counsel patients however, that the onset of action generally takes 30 days compared to 15 days for most NSAIDs. Some studies are evaluating the use of an intravenous loading dose of SAMe for five days before switching to the oral form in order to speed the onset of action. Interestingly, trials of oral SAMe have shown benefit in treating the symptoms of fibromyalgia whereas the intravenous formulation showed no significant benefit. More research is needed in this area to expound on these results.
SAMe
Adverse effects Flatulence Mild GI complaints Dry mouth Headache Insomnia Cautions Bipolar disorder: may cause hypomania Interactions Tricyclic antidepressants Selective serotonin reuptake inhibitors (SSRIs) Monoamine oxidase inhibitors (MAOIs) Levodopa Dosing Depression: 400-1600mg PO QD (200-400mg IV/IM QD) Osteoarthritis: 200mg PO TID (400mg IV QD) Fibromyalgia: 800mg PO QD SAMe is generally very well tolerated. Unlike many other dietary supplements, SAMe has been studied in clinical trials lasting up to 2 years in duration and in over 22,000 people cumulatively with few serious side effects. The most common complaints in people taking SAMe include flatulence, mild gastrointestinal complaints such as nausea, vomiting, diarrhea, and constipation, dry mouth, headache, and insomnia. SAMe should be used with caution in patients with bipolar disorder however due to reports of hypomania and one case of conversion to mania.
SAMe
Due to the serotonergic effect of SAMe, there is the potential for serotonergic symptoms when combined with other medications with serotonergic effects such as the tricyclic antidepressants, the SSRIs, MAOIs, tramadol, dextromethorphan, or meperidine. SAMe also causes the methylation of levodopa and may decrease the effectiveness of medications used to treat Parkinsons disease. Dosing of SAMe for depression ranges from 400-1600mg PO daily although most clinical trials were done with 1600mg daily. Dosing for other conditions is listed above.
St. Johns Wort

Common use Depression Standardization Hypericin 0.3% Hyperforin 3-5% Mechanism of action Inhibits reuptake of serotonin, norepinephrine, dopamine GABA effects Induces CYP3A4 (major), 2C9 (moderate), 1A2 (moderate) St. Johns wort (Hypericum perforatum) is most often used to treat mild to moderate depression and its associated symptoms. It is also being studied for use in seasonal affective disorder, premenstrual syndrome, obsessive compulsive disorder, and psychological symptoms associated with menopause. Extracts of St. Johns wort are prepared primarily from the flowers but may also include the leaves of the plant. Researchers used to think hypericin was the active ingredient, but now it is thought that the antidepressant activity is most likely due to hyperforin. Look for products that are standardized to both hypericin and hyperforin content. Hyperforins are though to inhibit the activity of serotonin, norepinephrine, and dopamine receptors and the uptake of gammabutyric acid (GABA) leading to the antidepressant effects. Hyperforin is also responsible for the induction of CYP isoenzymes. Preparations of St. Johns wort can induce CYP3A4 up to 98% leading to increased metabolism and decreased serum levels of many other medications. Hyperforin also induces CYP2C9 and 1A2 to a lesser degree. There appears to be no clinically significant effect on CYP2D6. Hypericin content is largely responsible for the photosensitivity associated with St. Johns wort.
St. Johns Wort

Effectiveness Mild to moderate depression Seasonal affective disorder Menopausal symptoms Most evidence suggests that St. John's wort is effective for improving mood and reducing insomnia and somatic symptoms of depression in patients with mild to moderately severe depression. St. Johns wort is more effective than placebo and some studies have shown it to be comparable to low-dose tricyclic antidepressants and the selective serotonin reuptake inhibitors fluoxetine, sertraline, and paroxetine. The effectiveness of St. Johns wort has been questioned after two large trials found it to be no better than placebo. The reason for the contradictory findings is not clear, however, one possibility is that these two negative trials were performed in psychiatric centers. Many previous St. John's wort trials were conducted in primary care settings. Patient characteristics may vary between primary care settings and psychiatric clinics, which could have resulted in different study outcomes. St. Johns wort is also being studied for the treatment of seasonal affective disorder (SAD) and psychological symptoms of menopause. Although the results are preliminary, St. Johns wort does appear to be more affective than placebo for the treatment of SAD. Women experiencing psychological symptoms of menopause may find some relief from St. Johns wort combined with black cohosh, although larger studies need to be done to confirm these findings.
St. Johns Wort

Adverse effects Nausea Allergic reactions Dizziness Insomnia Vivid dreams Restlessness Fatigue Dry mouth Photosensitivity Interactions (multiple interactions, this is an abbreviated list) Amitriptyline Benzodiazepines Digoxin Oral contraceptives Phenobarbital Phenytoin Protease inhibitors Warfarin Other serotonergic medications Dosing 300mg TID May take 3-4 weeks to see maximal effect Taper when discontinuing to avoid withdrawal effects
St. Johns Wort
St. Johns wort is generally well tolerated. Common side effects include nausea, dizziness, insomnia, vivid dreams, restlessness, fatigue, and dry mouth. Insomnia and vivid dreams can be lessened by taking St. Johns wort in the morning. Allergic reactions to St. Johns wort, such as erythroderma, have been reported although they are very rare. Photosensitivity may be caused by the hypericin content in St. Johns wort. It is recommended that light or fair-skinned people use sunscreen and other protective measures when exposed to sunlight. Sexual dysfunction has been reported with the use of St. Johns wort although to a lesser degree than the selective serotonin reuptake inhibitors. In general, St. Johns wort is better tolerated and has fewer side effects than tricyclic antidepressants. Interactions with St. Johns wort due to induction of the CYP450 enzymes are well documented and clinically significant. Use caution in elderly patients who are taking medications such as benzodiazepines, digoxin, phenobarbital, phenytoin, or warfarin. Patients with AIDS should avoid the use the St. Johns wort due to multiple drug interactions. There have also been reports of a serotonin-like syndrome in patients taking St. Johns wort together with other serotonergic medications. Dosing of St. Johns wort is usually 300mg three times a day but it may take 3-4 weeks to see a clinical effect. St. Johns wort should be tapered upon discontinuation to avoid withdrawal effects. Withdrawal effects may appear within 1-2 day after discontinuing St. Johns wort and are independent of dose and duration of use.
Chamomile
Common uses Insomnia Restlessness Dyspepsia Allergic rhinitis Active components Quercetin Apigenin Coumarins Mechanism of action Anti-inflammatory effects: Decreases prostaglandins and leukotrienes Inhibits histamine release Sedative effects: unknown German chamomile (Matricaria recutita) is commonly used for symptoms of insomnia, restlessness, dyspepsia, and allergic rhinitis. Topically chamomile can be used to hemorrhoids, allergic reactions, and preventing chemotherapy or radiation therapy induced mucositis. The active components of chamomile are quercetin, apigenin and various coumarins. Anti-inflammatory effects are due to the inhibition of cyclooxygenase and lipoxygenase which cause a decrease in production of prostaglandins and leukotrienes. Similar to xxx, quercetin can inhibit the release of histamine from mast cells. It is thought that apigenin also has effects on the release of histamine. The mechanism of action for the sedative effects of chamomile is unknown. Some preliminary research suggested that chamomile may affect GABA receptors in the central nervous system however subsequent research found no effect.
Chamomile
Effectiveness Unknown for most common uses Adverse effects Hypersensitivity reactions Eczema Interactions Warfarin CNS depressants Dosing Optimal dose unknown There is limited scientific evidence available to assess the effectiveness of chamomile for the conditions that it is most commonly used. Chamomile is frequently consumed in the form of tea which may have varying amounts of the active components. It has GRAS (Generally Recognized as Safe) status in the United States. The most common side effects seen with chamomile are hypersensitivity reactions or eczema in patients with allergies to the Asteraceae family which includes ragweed and daisies. Counsel patients with ragweed allergies to avoid the use of chamomile. Chamomile has a theoretical interaction with CNS depressants. No case reports of this interaction have been reported in humans. Due to the coumestan component of chamomile, it may increase bleeding time in patients taking warfarin. The clinical significance of this interaction is unknown.The optimal dose of chamomile is unknown due to lack of clinical studies to assess effectiveness.
Melatonin
Common uses Insomnia Jet lag Circadian rhythm disorders in blind children and adults with no light perception* *FDA indication Mechanism of action Natural hormone secreted from pineal gland Regulates circadian rhythms Darkness stimulates secretion Melatonin is an endogenous hormone produced by the pineal gland involved in regulating circadian rhythms. It is commonly used for various types of insomnia, jet lag, and shift-work disorder. Melatonin has a FDA indication as an orphan drug for treating circadian rhythm disorders in blind children and adults with no light perception. Darkness stimulates secretion of endogenous melatonin and light inhibits secretion. It is thought that melatonin enhances the binding of GABA receptors in the central nervous system. It has a short-lived and transient effect on alertness which advances the circadian rhythm. Onset of action is usually within 30 minutes and lasts from 1-4 hours with little if any hangover effect the next morning. Melatonin may also lower body temperature and blood pressure, promote relaxation, and decrease alertness as the body prepares for sleep. Note: Ramelteon (Rozerem) is a melatonin receptor agonist approved by the FDA in 2005 for the treatment of insomnia and is not equivalent to synthetic melatonin.
Melatonin
Effectiveness Insomnia: decreases sleep latency by 12 minutes (more effective in elderly) Jet lag: improves alertness and psychomotor performance
The best evidence for melatonin suggests that it improves insomnia in the elderly, especially if endogenous levels are low. Younger patients also report subjective improvement in sleep quality when taking melatonin; however, melatonin does not seem to improve objective measures of sleep, such as sleep latency, in these patients. Overall, melatonin reduces sleep latency by 12 minutes on average which may not to clinically significant for most patients with insomnia. There appears to be little if any effect on sleep maintenance unless sustained release products are used but the clinical evidence is inconclusive. The use of melatonin for jet lag may improve alertness and psychomotor performance but has little effect on drowsiness and fatigue. The greatest effect is seen when traveling over 5 or more time zones in an eastward direction. Melatonin must be administered in synchronization with the day/night cycle once you arrive at your final destination. Prophylactic use of melatonin prior to travel does not significantly advance the sleep/wake cycle.
Melatonin
Adverse effects Drowsiness Headache Dizziness Interactions CNS depressants Dosing Insomnia: 0.3-5mg QHS Jet lag: 2-5mg night of departure, then QHS for the next 2-5 days
Melatonin is very well tolerated and side effects are generally no more common than placebo. The most common side effects are drowsiness, headache, and dizziness. There are few clinically relevant interactions with melatonin. Theoretically, CNS depressants may cause additive sedation when used in conjunction with melatonin and should be used with caution. Dosing for insomnia ranges from 0.3-5mg taken within 30 minutes of desired time of sleep. The most common starting dose is 2mg which can be increased to 5mg on subsequent days if a beneficial effect is not achieved. Suggest immediate-release for people with difficulty falling asleep. For difficulty staying asleep, suggest sustained-release. Melatonin dosing for jet lag should be 2-5mg on the night of departure followed by the same dose for the next 2-5 days at bedtime. Counsel patients that melatonin does not induce sleep like other prescription sleep aids. Rather melatonin resets or shifts the natural circadian rhythm over a period of several days. When melatonin is used for jet lag, it usually takes 2-5 days to adjust to the new time zone. It may take 2-3 weeks to experience the full effect of melatonin when it is used for insomnia.
Valerian
Common uses Insomnia Anxiety Standardization 0.2-0.5% valerenic acid Mechanism of action May increase GABA activity by inhibiting an enzyme that metabolizes GABA Benzodiazepine-like effects Valerian (Valeriana officinalis) is commonly used for insomnia and anxiety disorders. The root and rhizome of the plant are utilized in preparing extracts. The exact components responsible for its sedative effect are unknown but most likely include the sesquiterpenes valerenic acid and valepotriates. There are several species of Valeriana with varying amounts of sesquiterpene content. Valeriana officinalis is the most often used in commercial preparations. The mechanism of action of valerian includes increase in gamma-aminobutyric acid (GABA) activity via inhibition of an enzyme that metabolizes GABA. This mechanism is primarily responsible for the benzodiazepine-like effects of valerian. In vitro studies have shown that valerian inhibits CYP3A4 but the clinical significance is unknown at this time. It appears that doses of >1000mg/day may cause modest inhibition of CYP3A4 whereas doses of 375mg/day have no effect.
Valerian
Effectiveness Reduces time to sleep onset in patients with insomnia Not as fast as benzodiazepines May take a few days to weeks to work
Valerian has sedative, hypnotic, and anxiolytic properties. It can reduce the time to sleep onset (sleep latency) as well as improve the quality of sleep. Valerian does not work as fast as benzodiazepines and may require several days to weeks to take effect. The greatest effect is seen when taken up to 2 hours before desired bedtime. In one study in elderly patients, valerian was not as effective as temazepam or diphenhydramine for causing sedation. Some evidence has shown the benefit of valerian for insomnia in patients who have recently withdrawn from benzodiazepines. Not all studies have shown beneficial effects however, and larger studies are needed to elucidate the effectiveness of valerian for insomnia in a larger population. The evidence for the use of valerian for anxiety is mixed. Some evidence supports the use of valerian for social anxiety however, other studies found no difference from placebo in patients with generalized anxiety disorder. Glass JR, Sproule BA, Herrmann N, et al. Acute pharmacological effects of temazepam, diphenhydramine, and valerian in healthy elderly subjects. J Clin Psychopharmacol 2003;23:260-8.
Valerian
Adverse effects Headache Nervousness Excitability Hepatotoxicity (rare) Interactions CNS depressants Benzodiazepines Dosing 400-900mg/day 2 hours before bedtime Taper when discontinuing Valerian is generally well tolerated. The most common side effects are headache, nervousness and excitability. Occasional valerian may cause insomnia, vivid dreams, dry mouth, and daytime drowsiness. Caution patients against driving or performing task that require alertness. There are several case reports of hepatotoxicity related to valerian in combination with other herbal supplements. It is unclear if valerian was the causative agent in these case reports. Therefore, if patients take valerian for an extended period of time, recommend periodic liver function tests. Valerian may have additive sedative effects when taken together with other CNS depressants. There is also a theoretical concern that valerian may have additive therapeutic and adverse effects when taken with benzodiazepines. Dosing is typically 400-900mg/day taken up to 2 hours before intended bedtime. There's some concern that valerian might cause a benzodiazepine-like withdrawal syndrome if discontinued suddenly, therefore it is recommended to taper the dose.
Black Cohosh
Common uses Hot flashes Premenstrual syndrome (PMS) Labor induction Standardization 1mg triterpene glycosides/20mg tablet 2mg triterpene glycosides/20mg tablet Mechanism of action Minimal phytoestrogen effects Competitive agonist activity at the serotonin 5-HT7 receptor
Black cohosh (Actaea racemosa) is most commonly used for treating menopausal symptoms such as hot flashes, night sweats, anxiety, and depression. Of note, black cohosh should not be confused with two unrelated plants, blue cohosh (Caulophyllum thalictroides) and white cohosh (Actaea alba), which have hepatotoxic effects. The commercial product Remifemin has been studied most in clinical trials. The original formulation was standardized to contain 1mg triterpene glycosides/20mg tablet but the newer formulation contains 2mg triterpene glycosides/20mg tablet. Other products may be standardized to different components or to a different concentration of triterpenes. The exact mechanism of action for black cohosh is unknown at this time. It was originally thought that black cohosh exerted its effects as a phytoestrogen, however, recent studies failed to demonstrate estrogenic effects. Black cohosh does not bind to estrogen receptors nor does it affect the levels of estradiol, leutinizing hormone, follicle-stimulating hormone, or prolactin. Black cohosh exhibits activity similar to the selective estrogen receptor modulators which may explain its estrogen-like activity. It may also exert its action through mixed competitive agonist activity at the serotonin 5-HT7 receptor. This would explain the positive effects of black cohosh on symptoms such as anxiety and depression.
Black Cohosh
Effectiveness Reduces moderate menopausal symptoms and hot flash frequency May be comparable to low-dose transdermal estradiol for relieving hot flashes Not effective for hot flashes in breast cancer survivors Several trials have demonstrated that black cohosh is effective in reducing the frequency and severity of hot flashes in postmenopausal women. In one trial, the commercial product Remifemin was found to be comparable to low-dose transdermal estradiol for relieving hot flashes. Research using other formulations of black cohosh however, is less consistent. The National Center for Complementary and Alternative Medicine (NCCAM) funded a one year, randomized, double-blind, placebo-controlled trial of black cohosh and found that it did not reduce the number or intensity or hot flashes. The North American Menopause Society (NAMS) recommends a trial of black cohosh for mild vasomotor symptoms related to menopause. They do not endorse the efficacy of black cohosh but rather base their recommendation on the relatively safe side effect profile. Similar to soy, black cohosh does not seem to be effective for relieving hot flashes in breast cancer survivors, however, it does not stimulate the growth of estrogen-dependent tumors in vitro experiments.
Black Cohosh
Adverse effects Headache Rash GI complaints Weight gain Liver damage (possible) Interactions Hepatotoxic medications CYP450 2D6 inhibitor Adverse effects related to black cohosh are relatively mild and include complaints of headache, rash, gastrointestinal discomfort, and some minimal weight gain. There have been several case reports of hepatoxicity in women using black cohosh however the causality is either unknown or weakly correlated to the supplement. Of note, blue cohosh (Caulophyllum thalictroides) and white cohosh (Actaea alba) both have hepatotoxic effects and may be confused with black cohosh. Patients should obtain supplements from reputable sources and report any signs of hepatic disease such as jaundice, unusual fatigue, or abdominal discomfort to their healthcare provider immediately. Due to the case reports of hepatotoxicity, it is advisable to avoid the concomitant use of other hepatotoxic medications which may include: acetaminophen, amiodarone, carbamazepine, methotrexate, and others. Black cohosh may also inhibit cytochrome P450 2D6 and interact with medications such as tricyclic antidepressants, antidepressants, beta blockers, antipsychotics, as well as other medications. The most common dose of black cohosh is 40-80mg/day standardized to provide 4-8mg triterpene glycosides. Note: Counsel patients that Remifemin has changed the standardization of their product and they now require only 20mg twice daily.
Dosing 40-80mg/day BID (1mg triterpene glycoside/20mg tablet) 20mg BID (2mg triterpene glycoside/20mg tablet)
Soy
Common uses Cardiovascular disease Hyperlipidemia Hot flashes Osteoporosis Diabetes Breast cancer Standardization: none Active components Genistein Daidzein Mechanism of action Isoflavones Soy (Glycine max) has been used for thousands of years as both a food and natural remedy. Therapeutic uses of soy include the prevention of cardiovascular disease, hyperlipidemia, hot flashes, osteoporosis, breast cancer, and diabetes. In fact, the FDA has approved the label claim 25 grams of soy protein a day, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease. Soybeans contain protein, carbohydrates, various oils, and isoflavones. Currently there is no standardization for soy products, but most will list the amount of soy protein in units of grams or grams/serving or isoflavone content in units of milligrams.
Soy
It is believed that the primary active components of soy are the isoflavones genistein and daidzein. Both of these isoflavones are hydrolyzed in the gut to the active forms. Daidzein is also converted to the estrogenic compound equol by gastrointestinal flora. The rate of conversion varies among people and 50% of the population does not produce equol. This may explain some of the population differences seen in clinical trials. Soy isoflavones are structurally similar to estradiol and bind both alpha and beta estrogen receptors. Beta estrogen receptors are predominantly found in the heart, vasculature, bone, and bladder and may be responsible for some of the beneficial effects of soy. Soy isoflavones may also have effects similar to the selective estrogen receptor modulators (SERMs). In premenopausal women, isoflavones may have an antiestrogenic effect because they displace endogenous estrogen. In contrast, isoflavones have a mild estrogenic effect in postmenopausal women. Effectiveness Breast cancer: may decrease incidence of cancer in Asian women Hyperlipidemia: decreases LDL by 3-5% Hot flashes: may modestly decrease severity and frequency in some women Osteoporosis: inconclusive; may increase bone mineral density Diabetes: more studies needed; may decrease A1c and insulin resistance Epidemiologic studies suggest that consuming a diet high in soy protein may decrease the incidence of breast cancer. Most of this research has been done in Asian women and there are some questions about whether the same benefit is seen nonAsian women. A few smaller studies with middle-aged women of non-Asian descent show no change in breast cancer rates. It appears that soy protein has the greatest effect on breast cancer prevention when it is consumed by premenopausal as compared to postmenopausal women. Most evidence shows that substituting 25-135 grams/day of soy protein for other dietary sources of protein, decreases LDL cholesterol by 3-5%. However, there appears to be no significant effect on triglycerides or HDL cholesterol. Some clinicians question whether reductions of this magnitude are clinically significant for most patients. Soy protein may have the greatest effect in patients with higher baseline total cholesterol levels.
Soy
In 1999 the FDA approved a health claim for soy products stating that a daily diet low in saturated fat and cholesterol and containing 25g of soy protein (about 6.25g /serving) may reduce the risk of heart disease. This claim was based on data from several clinical trials studying the effect of soy on reducing LDL cholesterol. The FDA claim does not include soy isoflavones due to conflicting results regarding effectiveness in clinical studies. Data on the effectiveness of soy for menopausal symptoms such as hot flashes and night sweats is inconclusive. According to an evidence report by AHRQ (Agency for Healthcare Research and Quality), most studies are unsuitable for meta-analysis due to high dropout rates and inconsistency in scales and indexes used to classify symptoms. Two thirds of the studies they reviewed either significantly or non-significantly reduced the frequency and duration of hot flashes, however, the other third demonstrated no difference or worse effects with soy protein and/or isoflavones. The most benefit, a reduction in hot flash frequency ranging from 7-40 percent, was seen with isoflavone supplements rather than soy protein. Explain to patients that eating soy foods or taking soy supplements might provide modest relief, but will not relieve all symptoms. Another factor to consider is that relief from hot flashes may not occur for up to two months. Unfortunately, soy does not seem to be effective for relieving hot flashes in breast cancer survivors. Studies regarding the use of soy for osteoporosis are inconclusive. Limitations of the studies include short study duration (usually less than six months), different patient populations (premenopause versus perimenopause), inconsistent study design, and differences in soy products and/or concentrations of isoflavones. Most studies with positive results used 80-90mg isoflavones or 40g of soy protein. A few preliminary studies in postmenopausal women with diabetes have shown that soy may decrease fasting blood glucose levels, hemoglobin A1c, and insulin resistance. More research is needed before recommending soy for adjunct treatment of diabetes. Balk E, Chung M, Chew P, et al. Effects of Soy on Health Outcomes. Summary, Evidence Report/Technology Assessment: Number 126. AHRQ Publication Number 05-E024-1, August 2005. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/epcsums/soysum.htm
Soy
Adverse effects Constipation Diarrhea Bloating Nausea Interactions May decrease warfarin effectiveness MAOI (monoamine oxidase inhibitors) Avoid if taking tamoxifen Women with estrogen-dependent cancers should avoid soy Dosing Hyperlipidemia: 20-50g/day soy protein Hot flashes: 20-60g/day soy protein or 34-76mg isoflavones/day Osteoporosis: 40g/day soy protein
Soy protein and isoflavone supplements are generally well tolerated. The most commonly reported adverse effects in clinical trials were mild gastrointestinal complaints such as constipation, diarrhea, nausea, and bloating. These complaints may vary with the formulation of soy being used, for example, soy protein shake, soy wafers, whole soybeans, etc.
Soy
There is some concern that the use of unopposed estrogens may increase the risk of endometrial cancer, however, most evidence suggests that dietary intake of soy phytoestrogens does not stimulate endometrial growth. In one study, concentrated isoflavone-containing supplements providing 120 mg/day of isoflavones for 6 months did not stimulate endometrial thickening. In contrast, another study found that taking 150 mg/day for 5 years did increase the risk of endometrial hyperplasia. Inform women that it is safest to use foods containing soy protein rather than concentrated supplements. The isoflavones found in soy may inhibit platelet aggregation so caution is advised in patients taking anticoagulant or antiplatelet agents. Fermented soy products such as miso and soy sauce contain tyramine and should be avoided in patients who are also taking monoamine oxidase inhibitors. Women who are taking tamoxifen or who have estrogen-dependent cancers should avoid the use of therapeutic doses of isoflavones. Phytoestrogens such as genistein and daidzein may have estrogenic effects that antagonize the action of tamoxifen or stimulate estrogen-dependent cancers. Although laboratory evidence suggests that phytoestrogens from soy can stimulate proliferation of normal human breast tissue there is no evidence that dietary soy increases the rate of breast cancer. In fact, dietary soy may prevent the development of breast cancer in some Asian populations. In general, it is advisable to use whole soy foods rather than supplements.
Saw Palmetto
Common use Benign prostatic hyperplasia (BPH) Standardization 80-90% fatty acids Mechanism of action Antiandrogenic Inhibits 5-alpha reductase Anti-inflammatory
Saw palmetto (Serenoa repens) is most commonly used for treating benign prostatic hyperplasia (BPH) but is also traditionally used for treating alopecia, increasing breast size, and as an aphrodisiac. The ripe fruit contains the active ingredients which are often standardized by fatty acid content. Formulations most often used in clinical trials are standardized to 80-90% fatty acids. Tea formulations relying on water extraction are likely ineffective due to limited fatty acids. The exact mechanism of action of saw palmetto is unknown. It is thought that the lipophilic extract may inhibit 5-alpha reductase and prevent conversion of testosterone to dihydrotestosterone (DHT). In vivo concentrations of testosterone, DHT and 5-alpha reductase however are unchanged in subjects taking saw palmetto orally. Saw palmetto is also thought to inhibit cyclooxygenase and lipoxygenase which may contribute to its anti-inflammatory activity.
Saw Palmetto
Effectiveness Possibly similar to 5-alpha reductase inhibitors Not as effective as alpha-1 blockers In clinical trials lasting up to one year, saw palmetto has been shown to reduce symptoms of BPH such as frequent urination, painful urination, hesitancy, urgency, and nocturia. It has also been shown to improve peak and mean urine flow and lower residual urine volume. Saw palmetto's activity appears to be prostate-specific. When compared to 5-alpha reductase inhibitors, saw palmetto had a similar effect on reducing patient-reported symptoms. Saw palmetto does not reduce overall prostate size but rather shrinks the inner prostatic epithelium. Unlike finasteride, saw palmetto has no effect on PSA levels. Not all trials with saw palmetto however have been positive. Selective alpha-1 blockers show superior efficacy when compared to saw palmetto. In addition, combining saw palmetto with a selective alpha1-blocker such as tamsulosin does not relieve symptoms any better than the alpha1-blocker alone.
Saw Palmetto
Adverse effects Dizziness Headache GI complaints Interactions Increased bleeding time (1 case report) Dosing 1-2g whole berries or 160-320mg lipophilic extract Takes 1-2 months to feel improvement Saw palmetto is generally well tolerated. The most common adverse effects are dizziness, headache, and gastrointestinal complaints such as nausea, diarrhea, and constipation. There is one case report of increased bleeding time in a patient taking saw palmetto prior to surgery. Symptoms resolved upon discontinuing saw palmetto. Due to this case report use caution in patients taking anticoagulant or antiplatelet medications. There is also some concern regarding sexual dysfunction in men due to the inhibition of 5-alpha reductase. To date this has not been reported with saw palmetto. The incidence of impotence is similar to placebo in studies and less than finasteride. Dosing in clinical trials is usually 160mg twice daily or 320mg daily using formulations with 80-90% fatty acids. Counsel patients that it may take 1-2 months to achieve improvement in BPH symptoms.
Ginseng
Common uses Fatigue Weakness Sexual dysfunction Cognitive function Diabetes Menopause symptoms Standardization Asian ginseng (Panax ginseng) American ginseng (Panax quinquefolius) Siberian ginseng (Eleutherococcus senticosus) Active components Ginsenosides Triterpinoid saponins Mechanism of action Increases resistance to environmental and psychological stressors Exact mechanism unknown
Ginseng
Ginseng (Panax ginseng) is considered an adaptogen which is defined as a substance that increases your resistance to environmental and psychological stressors. Ginseng is often used to combat fatigue and weakness as well as improve sexual and cognitive function. There has also been some recent interest in using ginseng to treat diabetes. Historically, ginseng was used for anemia, asthma, anxiety, enhancing strength and stamina, bronchitis, cancer, common cold, congestive heart failure, depression, influenza, and menopausal symptoms. There are several types of ginseng available and they are all different herbs. Panax ginseng, also known as Asian ginseng or Korean ginseng, is the most commonly used medicinal ginseng and will be the focus of this review. The root of Panax ginseng contains the active chemical components called ginsenosides (or panaxosides) that are thought to be responsible for the herb's medicinal properties. The root is dried and used to make tablets or capsules, extracts, and teas, as well as creams or other preparations for external use. Ginsenosides are biochemically complex and contain many different chemical entities, the most active of which are the triterpinoid saponins. It is thought that gensenosides may decrease stress via interactions with the hyperthalamic-pituitary-adrenal (HPA) axis and reducing serum cortisol levels. Another potential mechanism of action involves stimulation of natural killer cells and other immune modulators. Ginseng may also directly stimulate insulin secretion. It is unclear at this time if ginseng has any estrogenic effects.
Ginseng
Effectiveness Largely undetermined in clinical trials Well-being: Only evidence is for self-rated quality of life Sexual dysfunction: May improve symptoms of erectile dysfunction (1 study) Cognition: May improve some mental activities; no effect on memory Diabetes: May decrease fasting blood glucose (1 study) The data related to the clinical effectiveness of ginseng is inconclusive. Data regarding the use of ginseng to increase wellbeing shows no objective evidence of effectiveness for improving mood or well-being. Study participants did score higher however on self-reported quality of life. Although ginseng has no effect on reducing the number or severity of hot flashes, some women report improved quality of life in terms of fatigue symptoms. One preliminary study found a beneficial effect of ginseng on symptoms of erectile dysfunction. Topical formulations containing ginseng in combination with other herbs are being studied for the prevention of premature ejaculation. Ginseng may also have a beneficial effect on improving abstract thinking, mental arithmetic, and reaction times but does not appear to improve other cognitive functions and memory. A few small studies demonstrated improvement in memory however when ginseng was combined with ginkgo. One study in patients with type 2 diabetes showed evidence that ginseng may decrease daily fasting blood glucose levels. More studies are needed however before recommending ginseng for this use.
Ginseng
Adverse effects Insomnia Headache Gastrointestinal effects Interactions Warfarin Antiplatelet agents Loop diuretics Bitter orange Dosing Varied: 200-900mg/day Ginseng is generally very well tolerated. The most common side effect is insomnia so it is better to take ginseng in the morning or early afternoon. Other side effects include headache and mild gastrointestinal complaints such as diarrhea and stomach upset. Less common side effects may include mastalgia, vaginal bleeding, tachycardia, hypertension, decreased appetite, pruritis, and mania. Ginseng may increase clearance of the s-isomer of warfarin leading to decreased warfarin effectiveness. Increased monitoring of the INR is recommended in patients taking ginseng together with warfarin. Conversely, ginseng may decrease platelet aggregation leading to increased bleeding. There is also a potential for diuretic resistance when ginseng is used together with loop diuretics and there is one case report of nephrotoxicity. Bitter orange may increase the QT interval when used concomitantly with ginseng due to sympathomimetic effects. Dosing of ginseng depends on the condition being treated but usually falls within the range of 200-900mg/day. It is recommended to limit continuous use of ginseng to less than 3 months because long-term use may cause some hormonelike effects.
Resources
ConsumerLab.com Product evaluations and reviews Recalls and warnings Natural Products Encyclopedia Natural Medicines Comprehensive Database Provides clinical and scientific data on dietary supplements Natural product/drug interaction checker Search by disease or medical condition Consumer and professional information ConsumerLab.com provides product evaluations and reviews based on a specific topic each month similar to Consumer Reports. The staff procures samples from commercial sources and evaluates the products in terms of what the supplement is, how it claims to work, if it has the labeled amount of ingredients in each serving, dissolution, contamination, serving size, and if the product meets the labeling claims. This site also provides recalls and warnings for herbal products and other dietary supplements. ConsumerLab.com is a reputable source for comparing products and provides basic information on dietary supplements. The Natural Products Encyclopedia is also available for subscribers to the site. A yearly individual subscription costs $30. The Natural Medicines Comprehensive Database provides more detailed information on dietary supplements and herbal medicines. Each supplement review contains clinical and scientific data on effectiveness, common or traditional uses, safety and tolerability, side effects, dosing, and interactions with other supplements, conventional medications, medical tests, or other medical conditions. There is a natural product drug interaction checker that cross checks interactions between conventional medications and dietary supplements. They also provide short articles and continuing education programs on the use of supplements for diseases and medical conditions. Consumer information sheets are also available to download for patients. A yearly individual subscription is $92.
Resources
National Center for Complementary and Alternative Medicine (NCCAM) Supports research on complementary and alternative medicine Provides information on which modalities and therapies show evidence of efficacy Consumer and professional information Office of Dietary Supplements Consumer information on dietary supplements International Bibliographic Information on Dietary Supplements (IBIDS) Links to databases, fact sheets, trade organizations, and other websites The National Center for Complementary and Alternative Medicine (NCCAM) is part of the National Institutes of Health and supports research on complementary and alternative medicine. It provides information on which modalities and therapies show evidence of efficacy as well as general information on many herbs and health topics. This site allows access to Herbs At a Glance which can also be ordered free of charge from the website. The NCCAM provides both consumer and professional information. One of the consumer resources is a link to NIHSeniorHealth which provides information for the elderly on complementary and alternative medicine. The Office of Dietary Supplements is also a division of the National Institutes of Health and provides both consumer and professional information on dietary supplements. It also links to the International Bibliographic Information on Dietary Supplements (IBIDS) database which indexes scientific literature related to dietary supplements. The site also provides links to databases, fact sheets, trade organizations, and other websites.

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Geriatric

Pharmacy Review Module 20 : Complementary and Alterna<ve Medicine

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Complementary and Alternative Medicine

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Complementary and Alternative Medicine (CAM)

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Traditional Chinese Medicine (TCM)

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Traditional Chinese Medicine (TCM)

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Traditional Chinese MedicineModalities

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Traditional Chinese MedicineModalities

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Traditional Chinese MedicineHerbalism

Qualities of herbs: Nature Taste Affinity Action

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Copyright 2011 American Society of Consultant Pharmacists

Complementary and Alternative Medicine (CAM)Practice Types

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Complementary and Alternative Medicine (CAM)Usage

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Complementary and Alternative Medicine (CAM)Usage

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Complementary and Alternative Medicine (CAM)Usage

Regulatory IssuesDietary Supplements

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Regulatory IssuesDietary Supplement and Health Education Act (DSHEA)

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Regulatory IssuesStandardized Labels

Allowable claims for dietary supplements: Nutrient content Health Structure/function

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Regulatory IssuesQuality Control

Copyright 2011 American Society of Consultant Pharmacists

Regulatory IssuesQuality Control

Copyright 2011 American Society of Consultant Pharmacists

Regulatory IssuesQuality Control

Copyright 2011 American Society of Consultant Pharmacists

Copyright 2011 American Society of Consultant Pharmacists

Counseling Points: Recommending a Product

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Counseling Points: Re-evaluating Use

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Dietary SupplementsMost Common Uses

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Dietary SupplementsMost Common Uses

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Fish oil (omega-3 fatty acids)

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Fish oil (omega-3 fatty acids)

Copyright 2011 American Society of Consultant Pharmacists

Fish oil (omega-3 fatty acids)

Fish oil (omega-3 fatty acids)

Fish oil (omega-3 fatty acids)

Copyright 2011 American Society of Consultant Pharmacists

Copyright 2011 American Society of Consultant Pharmacists

Copyright 2011 American Society of Consultant Pharmacists

Copyright 2011 American Society of Consultant Pharmacists

Copyright 2011 American Society of Consultant Pharmacists

Copyright 2011 American Society of Consultant Pharmacists

Copyright 2011 American Society of Consultant Pharmacists

Copyright 2011 American Society of Consultant Pharmacists