Module 20 - Complementary and Alternative Medicine

7/31/2019 Module 20 - Complementary and Alternative Medicine

1/90

GeriatricPharmacyReview

Module20:

ComplementaryandAlterna


2/90

Copyright 2011 American Society of Consultant Pharmacists

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 on-line 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.


3/90


Content Experts

Current Content Expert:

Carla Bouwmeester, PharmD, BCPS

Assistant Clinical Professor

Northeastern University

Legacy Contributor:

Steven G Ottariano RPh

Clinical Pharmacy Specialist

Complementary MedicineVA Medical Center

Faculty Disclosure:

Carla Bouwmeester has no relevant financial relationships to disclose.

Steven G. Ottariano RPh ,has no relevant financial relationships to disclose.


4/90


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 amongstthe 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 dietarysupplement in the senior population.

Design a monitoring plan, for both safety and efficacy, for a senior taking a dietary supplement.


5/90


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 aregenerally considered to be set apart from Western conventional medicine. By definition, alternative medicine is used in placeof 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 andeffectiveness.

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 tomedicine practiced in the United States. Examples of whole medical systems include traditional Chinese medicine,

Ayurvedic medicine, and homeopathy.


6/90


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 particularsymptom can be used to treat conditions with similar symptoms. Although homeopathy utilizes naturalsubstances, 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 whenevaluating their vital force. The Law of susceptibility refers to the believe that a persons vital forcecan be disrupted by internal as well as external factors and produce symptoms of disease. Symptomsare 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 beingtested. Detailed records are kept on patient-reported symptoms, physical observations, and otherrelevant findings to ultimately determine the appropriate indication. Once a substance is identified andproven, the final remedy is prepared via serial dilutions. This practice is based on the Law ofinfinitesimals which states that only an infinitesimal amount of the original material is needed for theremedy. 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.


7/90


Homeopathy Remedies

Homeopathic remedies follow a nomenclature to indicate their relative potency. Dilutions of 1/10 are signified byX. 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 theingredient 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). Homeopathicremedies however, are often exempt from the rigorous testing for safety and effectiveness that is required forother prescription and OTC medications. The FDA contends that homeopathic remedies contain little or no activeingredient and pose little risk for adverse effects. Homeopathic medicines must be manufactured according to thespecifications 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 remediesare not required to have an expiration date and are exempt from testing for the identity and strength of the final

product.


8/90


Traditional Chinese Medicine (TCM)

TCM beliefs are based on the following theories:

QiChannels (meridians) and collateralsYin and yangFive phasesZang and fu

Traditional Chinese medicine, also known as TCM, has its origins over 2000 years ago during the Han dynasty. During thistime 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 becamethe basis of what we now consider herbal medicine in the context of TCM. In conjunction with herbal medicines, food therapyis also commonly prescribed. This may involve dietary recommendations or restrictions to promote a healthy diet or restorehealth and overall balance.


9/90


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 thatforms the core of TCM philosophy. Qi circulates throughout the body along channels or meridians and associatedcollaterals. 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 interconnectedand continuous as each gives rise to the other. Zang fu relates bodily functions with yin and yang to describe theirinteractions 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 rememberthat zang fu organs describe function rather than anatomy. The organs work together to regulate functions of the body andare 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. TCMpractitioners may start by interviewing the patient to gain an understanding of their symptoms and general emotional andphysical 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.


10/90


Traditional Chinese MedicineModalities

Traditional Chinese Medicine (TCM) includes the following modalities:

Herbal medicineFood therapy

AcupunctureMoxibustionAuriculoacupuncture

AcupressureCuppingTui na

Qigong

Acupuncture is one of the most well know practices of TCM after herbal medicine. In the 2007 National Health Interview Survey, anestimated 3.1 million adults in the U.S. used acupuncture in the previous year. Acupuncture involves the insertion of thin needles intospecific locations on the body along the meridians (see acupuncture map above). Moxibustion is often practiced in conjunction withacupuncture and involves the burning of dried Chinese mugwort above acupuncture sites. The smoldering mugwort is applied to theend of acupuncture needles, rolled into cigarette-like tubes and held over acupuncture sites, or placed in cones which are applieddirectly to the skin. Moxibustion is believed to increase circulation to the site and provide a warming effect. Also related toacupuncture is the practice of auriculoacupuncture which involves placing needles in specific areas of the ear. The auricle of the ear isthought to have an appearance similar to an inverted fetus. Detailed auricle maps relate areas on the ear to specific structures andfunctions of the body.


11/90


Traditional Chinese MedicineModalities

In addition to acupuncture, TCM utilizes various forms of external manipulation or massage to help restore harmoniousrelationships 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 alongcertain 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 andremoved before being placed on the back, creating suction as air within the sphere cools. When oil or lotion is applied to theskin 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 stressand improve the circulation of qi. This may be particularly helpful for the elderly patient.


12/90


Traditional Chinese MedicineHerbalism

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 fixedcombination but can also be taken individually or as part of a customized combination. Herbal remedies may contain plant, animal, ormineral constituents (i.e. powdered ginseng, ground deer antler, or oyster shells). Traditionally, dried herbs are prepared as tea, butsome 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 tolower metabolism or reduce gas and bloating. Herbs are also classified by taste and have either sour, bitter, sweet or bland, spicy, orsalty qualities. Affinity refers to the zang fu organ system where the herb has the greatest effect, whereas action" describes theprimary 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, adversereactions, and interactions can be extrapolated from research done on the individual herbal components, but effectiveness may differwhen herbs are used in fixed combinations. Research is underway to examine the effects of fixed combination herbals (for moreinformation, go to http://nccam.nih.gov/research/ ).

Qualities of herbs:

NatureTasteAffinityAction


13/90


Ayurveda

Doshas

Vata (wind/spirit/air)Pitta (bile)Kapha (phlegm)

Ayurveda evolved in India and is derived from theSanskrit words ayus and veda which mean thescience 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 beclassified 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 functionsand activities. Imbalances in the doshas, caused by stress, an unhealthy lifestyle, diet, or bacteria, lead to physicaland psychological illness. Such imbalances can be corrected by exercise, healthy eating habits, eliminatingimpurities, reducing stress, and increasing harmony.

Ayurvedic practices include yoga, meditation, massage, dietary recommendations, and herbal therapies. There hasbeen some concern about Ayurvedic remedies being contaminated with heavy metals and potentially toxicingredients. Therefore, it is important to obtain products from reputable and trusted sources.


14/90


Complementary and Alternative Medicine (CAM)Practice Types

CAM practices:

Biologically-basedEnergy medicineManipulative and body-basedMind-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 ofbalance in the presence of disease or illness. Examples of energy medicine include magnet therapy, healing touch, andReiki.

Manipulative and body-based practices include massage, spinal manipulation, and reflexology. These modalities focus onthe 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 ofthis modality include meditation, yoga, tai chi, prayer, placebo effect, imagery, and creative outlets such as writing, poetry,music, and art.


15/90


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 isgreatest 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 85and 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. December2008.


16/90




17/90



Nonvitamin, nonmineral natural products are the most commonly used CAM modalities in the 2007 study. The most popular naturalproducts were fish oil/omega 3, glucosamine, echinacea, flaxseed, ginseng, ginkgo, chondroitin, garlic, and coenzyme Q-10. Peoplereported 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 bythe media and results of scientific studies. It is important to monitor media coverage of herbal supplements in order to be prepared toanswer questions for clients regarding safety and effectiveness.


18/90


Regulatory IssuesDietary Supplements

Dietary supplements

VitaminsMineralsEnzymesAmino acidsHerbsOther botanicalsOther 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-the-counter (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.


19/90


Regulatory IssuesDietary Supplement and Health Education Act (DSHEA)

Dietary Supplement and Health Education Act (DSHEA)

Passed in 1994Definition of dietary supplementsMinimal labeling requirementsManufacturer is responsible for controlling qualityand safety

Standardized labels should include:Statement of identityNet quantityStructure/function claimDirectionsSupplement Facts panelOther ingredientsManufacturer name and address

Originally, vitamins and minerals were not classified as drugs in the Food, Drug, and Cosmetic Act of 1976. In the early1990s consumers were concerned that the Food and Drug Administration (FDA) would tighten control of dietary supplementsand limit their availability. In response to this concern the Dietary Supplement and Health Education Act, commonly knownas DSHEA (pronounced dee-shay) was passed in 1994.

Under DSHEA, dietary supplements were classified as foods rather than medications and fall under the regulatory authorityof 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 listedingredients. 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.


20/90


Regulatory IssuesStandardized Labels

Allowable claims for dietary supplements:

Nutrient contentHealthStructure/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. Examplesinclude 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, theymay not claim the supplement is effective for the prevention or treatment of disease. For example, a claim that glucosaminehelps 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/functionclaims must also contain a disclaimer statement that the FDA has not evaluated the claim.


21/90


Regulatory IssuesQuality Control

Adulteration concerns

Wrong ingredientProducts do not contain ingredients in the listed amountsContains unlisted dietary supplementsContains prescription medicationsContamination

Heavy metalsPesticidesBiologicalQuality control issues are of particular concern for dietary supplements. Although the FDA was given authority to establishGood 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 oreffective.

Adulteration remains a serious concern especially for products manufactured outside of the United States. Of particularconcern are products advertised to enhance sexual function which often contain phosphodiesterase inhibitors or theiranalogs. 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 thatinclude 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, orprocessing the product. Examples include lead contamination in some zinc lozenges, arsenic in a combination herbalproduct, or high levels of pesticide in an herbal concoction.


22/90



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 strengthsConsumerLab.com

Private companyProducts evaluated for quality, purity, and identity of listed ingredients and strengthsAmerican Herbal Products Association

National trade associationIssues recommendations for industry-wide self regulationPublishes Herbs of CommerceThere are several ways for healthcare professionals to help patients identify quality dietary supplements. The DietarySupplement 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. Supplementsare tested for accurate listing of the ingredients on the label in the declared amounts and strengths. The USP also looks atthe conditions under which the supplements are produced to ensure they meet good manufacturing practice standards. If thesupplement meets the USP standards, the manufacturer can include the DSVP seal on the label.


23/90



Similarly, ConsumerLab.com evaluates dietary supplements for quality issues such as purity, strength and identity of listedingredients, and bioavailability. Products are either submitted by the manufacturer or purchased by ConsumerLab.com forevaluation. 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-wideself-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.


24/90


Regulatory IssuesSafety

MedWatch

Report serious adverse eventswww.fda.gov/Saftey/MedWatchDietary Supplement and Nonprescription Drug Consumer Protection Act of 2006

Requires manufacturers to provide contact information on product labelManufacturers must notify the FDA of any serious adverse eventIdentifying safety concerns with dietary supplements is difficult because few adverse events are reported to the FDA and theinformation 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 casereports in the scientific literature.

In order to increase reporting of adverse events related to dietary supplements, Congress passed the Dietary Supplementand Nonprescription Drug Consumer Protection Act at the end of 2006. This act requires manufacturers or distributors to listtheir 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.


25/90


Counseling Points: Recommending a Product

What are your goals for taking this supplement?Promote healthPrevent/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 trendhowever to use supplements in the prevention and treatment of disease. This is especially true in times of economicadversity. The pharmacist has a unique opportunity to screen patients for appropriate use of dietary supplements and alsorefer 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 supplementsfor duplication of therapy. Dietary supplements may have similar pharmacologic effects to some prescription medicationsand 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 orbreastfeeding women, or those with compromised immune systems. Each person who is considering the use of a dietarysupplement should speak with a healthcare provider, such as a pharmacist, to determine the products safety, effectiveness,and potential side effects.


26/90


Counseling Points: Re-evaluating Use

Re-evaluate herbal use if you:

See no effect after several monthsNeed surgery/invasive proceduresHave cancerStart chemotherapyHave a change in medical conditionStart/discontinue other medicationsBecome pregnantBreastfeedOnce 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 sideeffects emerge or the condition worsens, the supplement should be discontinued. It is also important to note that someadverse 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 isscheduled for surgery or invasive procedures (such as a colonoscopy, tooth extraction, etc.), all dietary supplements shouldbe reviewed to determine if they affect the patients risk of bleeding. Some supplements such as ginkgo should be stopped10-14 days prior to surgery.

There are some concerns about the use of dietary supplements by people who have cancer or are undergoingchemotherapy. Some supplements are purported to be immune stimulants and may counteract the therapeutic effects ofchemotherapy. Similarly, studies on the use of antioxidants during chemotherapy have shown conflicting results. The use ofany 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 toremind patients not to share dietary supplements with family members who may become pregnant or are breastfeeding.


27/90


Dietary SupplementsMost Common Uses

Digestive Health

Constipation

Flaxseed*Dyspepsia

ChamomileGinger

Motion sicknessGinger*

Cardiac Health

HyperlipidemiaFish oil*GarlicSoyHypertension

Garlic*Fish oilPeripheral arterial disease

Ginkgo

Respiratory Health

Allergic rhinitisChamomileCommon coldEchinacea*

Bone & Joint Health

Osteoarthritis

Chondroitin*Glucosamine*

SAMeOsteoporosisSoyRheumatoid arthritisFish oil

Eye Health

GlaucomaGlucosamine

Cognitive & MentalHealth

AnxietyKava*ValerianCognitive functionFish oilGinkgoGinsengDementiaGinkgo*DepressionFish oilSAMe*St. Johns wort*InsomniaChamomile*Melatonin*Valerian*VertigoGinkgo

Womens Health

Menopausal symptoms

Ginseng

Hot flashesBlack cohosh*Red clover*Soy*


28/90


Dietary SupplementsMost Common Uses

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 commonuses, standardization, active components, mechanism of action, effectiveness, adverse effects, interactions, and dosing ofeach supplement.

Mens Health

Benign prostatic hyperplasiaSaw palmetto*

Miscellaneous

FatigueGinseng*

Sexual dysfunctionGinseng


29/90


Fish oil (omega-3 fatty acids)

Common usesHypertensionHypertriglyceridemiaCardiovascular disease preventionMental development (EPA/DHA)Rheumatoid arthritisBipolar disorderDepressionStandardizationEicosapentaenoic acid (EPA)Docosahexaenoic acid (DHA)Alpha-linolenic acid (ALA)plant derivedMechanism of actionAnti-inflammatoryDecrease platelet aggregationVasodilationDecreases triglyceridesFish 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 anddepression. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in infant formulas and baby foods toenhance 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 inshrimp, 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.


30/90



Alpha-linolenic acid (ALA) is the plant derived omega-3 precursor to DHA and EPA. It has some beneficial cardiac effects butmay 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 decreasedvasoconstriction. 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 VLDLclearance 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.


31/90



Effectiveness

Hypertension: slight decrease (2-5mm mercury)Hyperlipidemia

Decreases triglycerides (20-30%)Slightly increases LDL (5-10%)

Mental developmentInfants: some increase in cognitive developmentDementia: insufficient evidence

Several trials have confirmed the antihypertensive effects of fish oil. The effects appear to be dose-dependent but usually donot exceed 2-5mm mercury. DHA may contribute a greater effect than EPA for this indication. The clinical effectiveness ofthis 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 isstandardized to 465mg EPA and 375mg DHA in each 1 gram capsule. Various dietary supplements are also available over-the-counter but may have different side effects (due to manufacturing processes) and varying concentrations of EPA andDHA. Overall, fish oil may decrease triglyceride levels by 20-30%. There is some concern however that fish oil will alsoincrease 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 believedthat 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 beneficialeffect when combined with conventional therapies for the symptoms of depression associated with bipolar disorder but hasno 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 someepidemiological studies.


32/90



Adverse effects

Fishy burp or aftertasteHalitosisHeartburnLoose stoolInteractions

Antiplatelet agents or anticoagulants>3g can inhibit platelet aggregation

Vitamin A toxicityDosing

PreventionAmerican Heart Association: 2 servings/weekWorld Health Organization: 0.3-0.5 grams daily

Therapeutic1-4 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 somepatients. Enteric coated fish products or storing them in the freezer may also help reduce these bothersome side effects. Atvery 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 studieshave 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.


33/90



Recently there has been concern about the level of mercury contamination in fatty fish. Many of the fish oil productscurrently 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. Thesigns 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 farm-raised salmon and has carcinogenic, immunosuppressive, and toxic central nervous system effects. It is recommended tolimit 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. Someclinical studies have found that doses greater than 3 grams can inhibit platelet aggregation. However, other evidencesuggests fish oil in doses up to 6 grams daily does not significantly affect bleeding time. Overall, fish oil has less effect onbleeding than a daily dose of aspirin. Advise patients to use high-dose fish oil cautiously if they take other antiplatelet oranticoagulant 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 dietaryauthorities also recommend consuming alpha-linolenic acid, from sources such as tofu, soybeans, walnuts, flaxseed oil, orcanola oil. The World Health Organization provides a more specific recommendation of consuming 0.3-0.5 grams of EPA andDHA 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.


34/90


Garlic

Common uses

HypertensionHypercholesterolemiaColorectal cancerTick bitesStandardization

Varied or absent1.5% alliin content (clinical studies)Active components

AllicinAjoeneS-allyl-L-cysteinOther organic sulfur compounds

Mechanism of action

Inhibits platelet aggregationIncreases fibrinolysisInduces 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. Somepreliminary data suggests that garlic may be beneficial in preventingcolorectal 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.


35/90


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 enzymeallinase and produces allicin (pronounced allisun). Allicin is the odoriferous compound that gives garlic its characteristicsmell. Allicin is unstable and is quickly converted to compounds such as ajoene and other sulfur-containing chemicals. Thetherapeutic effects of garlic are attributed to allicin, ajoene, and other organic sulfur-containing components such as s-allyl-L-cysteine.

S-allyl-L-cysteine may inhibit hepatic cholesterol synthesis which is the purported mechanism for the cholesterol loweringeffects of garlic. Garlic may also inhibit platelet aggregation and increase fibrinolysis. It appears that raw garlic has strongerantiplatelet 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 endothelium-

derived relaxation factor (EDRF) or nitric oxide. This leads to vasodilation and the relaxation of smooth muscle.


36/90


Garlic

Effectiveness

HyperlipidemiaEarly studies showed reduction of TC, LDL, triglyceridesMore recent studies showed no cholesterol effect

HypertensionReduces 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 studiesshow that a variety of garlic preparations do not significantly reduce total cholesterol, LDL cholesterol, or other lipidconcentrations.

More promising research focuses on the use of garlic to reduce blood pressure. Garlic has shown some benefit in thetreatment of hypertension. Systolic blood pressure may be reduced by 8% and diastolic pressure by 7% in normotensive andhypertensive 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.


37/90


Garlic

Adverse effects

Breath and body odorHeartburnFlatulenceNausea/vomitingContact dermatitisSpontaneous bleeding (rare)Interactions

WarfarinAntiplatelet agentsProtease inhibitors3A4 substratesDosing

600-1200mg extract in divided doses4g 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 sideeffects 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 electivesurgery.


38/90


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 relativestrengths of the active ingredients in each type of supplement. Garlic also substantially decreases the plasma concentrationsof 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 channelblockers, 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 isimportant to note that active constituents vary widely in different garlic supplements. Some odorless preparations maycontain no active ingredients.


39/90


Flaxseed

Common uses

ConstipationDiabetesHot flashesHypercholesterolemiaActive components

Soluble fiberAlpha-linolenic acidMechanism of action

Soluble fiber acts as a bulk forming laxativeFiber content increases fecal excretion of bile salts, increasing bile acid synthesisLignan (phytoestrogen) content has weak estrogenic and antiestrogenic effectsFlaxseed (Linum usitatissimum) is both a food and dietary supplement commonly used for constipation, cardiovasculardisease, 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 ableto convert very small amounts of ALA into the more unsaturated fatty acids eicosapentaenoic (EPA) and docosahexaenoicacids (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 contentincreases 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 hotflashes.


40/90


Flaxseed

Effectiveness

Constipation: No clinical researchDiabetes: Based on one study, a specific lignan extract reduced A1c but had no effect on fasting blood sugarHot flashes: 40 grams crushed flaxseed daily reduced hot flashes by 35% and night sweats by 44%; 25 grams in bakedgoods 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 importantto 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 buthad no effect on fasting blood sugar or circulating insulin levels. Due to the reduced fatty acid content of the extract therewas no beneficial effect on cholesterol levels. Caution patients that flaxseed should not replace other pharmacologic andnon-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 baselinesymptoms 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 othersshowed no difference from placebo (wheat germ). Studies with lower flaxseed content in the form of baked goods showedno 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 withnormal 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 densitylipoprotein (HDL) or triglycerides, however, defatted flaxseed extract may slightly increase triglycerides secondary todecreased omega-3 fatty acid content.


41/90


Flaxseed

Adverse effects

BloatingFlatulenceAbdominal painDiarrheaBleeding (rare)

CautionsTake with fluid to prevent bowel obstructionRaw or unripe flaxseed may containcyanogenic glycosides40 grams of flaxseed contains 16 grams of fatand ~200 calorie

DosingDiabetes: 600 mg lignan extract threetimes daily (provides 320mg lignans)Hot flashes: 40 grams crushed flaxseeddailyHypercholesterolemia: baked goodswith 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 ofconstipation or in very rare cases, bowel obstruction.

Flaxseed may inhibit platelet aggregation and increase the risk of bleeding when taken in large doses (usually greaterthan 50 grams per day). Caution patients who are taking antiplatelet or anticoagulant medications about the potentialinteraction with flaxseed.

Raw or unripe flaxseed may contain cyanogenic glycosides. These compounds are undetectable when flaxseed isconsumed 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 flaxseedcontain 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 patientsutilized a specific lignan extract that provided 320 lignans daily.


42/90


Ginger

Common uses

Motion sicknessDyspepsiaLoss of appetiteRheumatoid arthritisActive components

GingerolGingerdioneShogaolGalanolactoneVolatile oils (various)Mechanism of action

May affect serotonin receptors in the digestive tractMay inhibit cyclooxygenase and lipoxygenase

Ginger (Zingiber officinale) is commonlyused for motion sickness, loss of appetite,and some anti-inflammatory conditions suchas rheumatoid arthritis. It is also used for

morning sickness in pregnant women and insome settings for chemotherapy-inducednausea and vomiting.

The active components of ginger includegingerol, gingerdione, shogaol,galanolactone and other volatile oils. Theamount of each component variesdepending on the preparation of the ginger(i.e. dried root, fresh, powdered).

The exact mechanism of action of ginger isunknown at this time. It is thought that

ginger may affect the 5HT3 serotonin

receptors in the digestive tract in a mannersimilar to other antiemetics. Anotherproposed mechanism is the inhibition of thecyclooxygenase and lipoxygenasepathways. This mechanism may beresponsible for the purported anti-

inflammatory effects of ginger.


43/90


Ginger

Effectiveness: unknown

Adverse effects

BloatingFlatulenceHeartburnDiarrheaInteractions

AnticoagulantsAntiplatelet agentsDosing

1-4 grams dailyThere 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 iscontroversial. 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 whenconsumed in large doses.

There is a theoretical interaction between ginger and anticoagulants or antiplatelet medications. Ginger can increasebleeding time by inhibiting thromboxane and decreasing platelet aggregation. Counsel patient to avoid this combination andinform healthcare worker prior to any surgical procedures.

The recommended dose of ginger is 1-4 grams of dried root per day.


44/90


Echinacea

Common usesColdsRespiratory infectionsStandardization: none

Mechanism of action

Stimulation of non-specific immune systemAnti-inflammatory effects

Echinacea, also known as the purple coneflower, is one of the most well-known and popular dietary supplements on themarket 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 echinaceastimulate the non-specific immune system, however, no effect is seen in the immune system of healthy volunteers. Therehas been recent speculation that the effects of echinacea are due to possible anti-inflammatory effects rather than immuneeffects.


45/90


Echinacea

Effectiveness

Likely safe but ineffectiveMay 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 recentmeta-analysis found that echinacea decreased the incidence of developing a cold by 58% and the duration by 1.4 days. Theclinical significance of this finding is unknown. There is no evidence that the chronic use of echinacea will prevent thedevelopment of the common cold.

The bottom line in terms of effectiveness is that echinacea islikely 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 usingthis species.

Adverse effects

GI effectsTingling sensation on tongueHeadacheAllergic reactionsContraindications

Ragweed allergyHistory of asthma, atopy, allergic rhinitisSevere autoimmune disease

InteractionsInhibits 1A2Inhibits intestinal 3A4Induces hepatic 3A4

Dosing

Initiate therapy at the onset of cold symptomsContinue therapy for 10-14 days


46/90


Echinacea

Adverse effects of echinacea are very mild and include complaints of mild gastrointestinal discomfort, a tingling sensation ofthe 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 theclassic 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 typehave 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 CYP1A2 however, the clinical significance is unknown. Although echinacea inhibits intestinal CYP 3A4 it also induces hepaticCYP 3A4 and the effects may cancel each other. Drug interactions are a theoretical concern at this point but it would beprudent 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.


47/90


Chondroitin

Common uses

OsteoarthritisOsteoporosisIschemic heart diseaseMechanism of action

Glycosaminoglycans (GAGs) act as substrates for the joint matrix structure of cartilagePossible antiatherogenic properties (animal studies)Effectiveness

Modest to possibly insignificant reduction in pain from osteoarthritis of the kneeChondroitin 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 heartdisease and osteoporosis.

Chondroitin is composed of large glycosaminoglycans (GAGs) that act as substrates for the joint matrix structure of cartilageand is found in most cartilaginous tissues. Chondroitin may also have some protective effects via inhibiting the enzymesresponsible 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. Patientsshowed improvement in pain scales and global functioning after several weeks of treatment. A particular combination ofchondroitin, glucosamine, and manganese also showed improvement in both subjective and objective pain scores in patientswith 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 theknee (placebo rate >60%).


48/90


Chondroitin

Adverse effects

HeartburnNauseaCautions

Produced from bovine cartilagepossible contaminationPotential anticoagulant effectEnsure manganese content does not exceed tolerable upper limit of 11mg per dayDosing

200-400mg two or three times dailySingle daily dose of 1000-1200mgIntermittent dosing: 3 months of treatment, 3 months of no treatment, then another 3 months of treatmentChondroitin 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 thesupplements 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 transmitteddisease related to chondroitin.

Chondroitin is a small component of a heparinoid and may theoretically have anticoagulant effects. There are case reports ofincreased INRs in patients taking warfarin together with glucosamine and chondroitin combination products. Glucosamine isalso 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 notexceed the tolerable upper limit of 11mg per day.


49/90


Glucosamine

Common use

OsteoarthritisJoint painGlaucomaMechanism of action

Stimulates metabolism of chondrocytesPossible disease-modifying effectEffectiveness

Improves pain and functionality in patients with osteoarthritis of the kneeGlucosamine, 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 ofthe different salt forms. Glucosamine can be derived from the exoskeletons of shrimp, lobster, and crabs or madesynthetically. 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 proteinsynthesis 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 notrelieve acute flare-ups. There is little evidence supporting the use of glucosamine for osteoarthritis of other joints such as thehip or lower back.


50/90


Glucosamine

Adverse effects

Mild GI complaintsAltered glucose metabolismInteractions

Warfarin: increased INRShellfish allergyDosing

Sulfate vs. HCl saltSulfate moiety may be active ingredientGlucosamine 500mg TID or 1500mg QDGlucosamine 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 inthe 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 onwarfarin to avoid the use of glucosamine or use with extreme caution and monitor INRs whenever they increase or decreasethe glucosamine dose.


51/90


Glucosamine

There is also concern of hypersensitivity reactions to glucosamine in patients with shellfish allergies, however there are nodocumented reports. Allergic reactions in people with shellfish allergy are caused by an IgE response to the meat ofshellfish, not to antigens in the shell. Patients with severe shellfish allergies should avoid use of glucosamine as aprecautionary 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 withglucosamine 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 notedthat the length of this trial was too short, there was no placebo group, and the dosing was three times daily rather than theonce 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.


52/90


Kava

Common uses

AnxietyStressEffectiveness

Possibly similar to benzodiazepinesStudies contained highly concentrated extractsAdverse effects

GI upsetDizzinessHeadacheHepatotoxicity

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 forceremonial purposes. It was discovered by Captain Cook who named the plant intoxicating pepper and introduced it to therest 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 butcontained 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 hasresulted 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 regularbasis in South Pacific islands however without incident of hepatotoxicity. Due to the potentially fatal adverse effects, do notrecommend the use of kava on a routine basis. If patients continue to use kava, recommend routine liver function tests toscreen for hepatotoxicity.


53/90


Ginkgo

Common uses

DementiaCognitive functionPeripheral arterial disease (PAD)Intermittent claudicationRaynauds syndromeVertigoStandardization

Flavonoid glycosides: 25-26%Terpenoids: 6%Mechanism of action

Antioxidant activity reduces oxidative damage to tissuesAnti-inflammatory propertiesInhibits 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 thousandyears. 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 ofdementia including vascular dementia, Alzheimers disease, and mixed dementia. Several studies have also examined therole of ginkgo in improving circulatory flow for primary or secondary prevention of stroke and its complications. Thecerebrovascular 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 Raynaudssyndrome.


54/90


Ginkgo

Ginkgo may have some beneficial effect in preventing the progression of diabetic retinopathy, however, it may affect bloodglucose 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 theycontain 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 oxidativestress 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 A2and thromboxane B2 thereby inhibiting platelet aggregation.

Effectiveness

Ginkgo Evaluation of Memory (GEM) study

Randomized, double-blind, placebo-controlled trialLarge, multicenter study (3,000 participants)Enrollment

75 years or older (mean age 79)No cognitive impairmentMild cognitive impairment


55/90


Ginkgo

Exclusion CriteriaCholinergic enhancer useBleeding disordersNeurodegenerative diseaseUse of ginkgo prior to study

Primary outcomeIncidence 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 120-240mg daily of a standardized ginkgo extract can modestly improve cognitive function in patients with Alzheimer's-related andother forms of dementia. However, another study in patients with more advanced Alzheimers disease and neuropsychiatriccomplications showed no benefit. In order to resolve this conflict the Ginkgo Evaluation of Memory (GEM) study waslaunched in 2000.

GEMThe GEM study enrolled more than 3,000 participants age 75 or older with mild or no cognitive impairment. The mean agewas 79 years and 46% of the participants were women. Study participants were followed on average for 6.1 years with amaximum of 7 years. They were given 120mg capsules of ginkgo biloba extract twice daily or matching placebo. The studywas 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 thestudy 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 ofdementia 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.


56/90


Ginkgo

Questions remain regarding the use of ginkgo to prevent dementia in younger patients as well as the active treatment ofAlzheimers 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 complaintsAllergic reactionsBleedingInteractions

Antiplatelet agents or anticoagulantsMedications that lower the seizure thresholdDosing

40-80mg TIDMay need higher doses for claudicationThe adverse effects related to ginkgo are relatively mild. The most commonly reported complaint is mild gastrointestinalupset 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 ginkgotoxinto safe levels, however this practice is not recommended. Most commercial formulations are prepared from leaves or leafextracts which contain little or no ginkgotoxin. Evidence linking ginkgo to seizures is inconclusive, however, it is prudent tosuggest caution to those with seizure disorders or patients taking other medications that may lower the seizure threshold.


57/90


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 areconcomitantly taking non-steroidal anti-inflammatory medications. Monitor the INR and signs and symptoms of bleedingclosely for any patients who are taking warfarin and ginkgo. Ginkgo should be discontinued 7-10 days (absolute minimum of36 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 isimportant to remind patients that it may take 6-8 weeks to see any improvement in cognitive function. Higher doses may beneeded for treating intermittent claudication.

Note: In vitro studies provide conflicting data on the effect of ginkgo on the CYP450 system. There are no clinicallysignificant interactions between ginkgo and the CYP450 system.


58/90


SAMe

Common uses

DepressionOsteoarthritisFibromyalgiaMechanism of action

Influences neuronal membrane fluidityIncreases serotonin turnoverIncreases 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 iscommonly 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 varioushormones, proteins, and medications. SAMe synthesis is also related to folate and vitamin B12 metabolism. When patientsare folate or vitamin B12 deficient, there are lower serum concentrations of SAMe. The clinical significance of thisassociation 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 dopaminelevels which may contribute to its antidepressant effects. SAMe also has some anti-inflammatory and analgesic effects.


59/90


SAMe

Effectiveness

DepressionIV: similar to tricyclic antidepressantsPO: 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 forup to 30-days. Of note, the onset of symptom alleviation was after 1-2 weeks. Short-term administration of intravenousSAMe was also studied in combination with oral tricyclic antidepressants to shorten the onset of action. Trials of oral SAMeshow some benefit for the treatment of major depression but are limited by study design, small sample sizes, and poormethodology.

Several clinical trials have shown that oral SAMe is superior to placebo and similar in efficacy to the non-steroidal anti-inflammatory 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 onsetof action generally takes 30 days compared to 15 days for most NSAIDs. Some studies are evaluating the use of anintravenous 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 intravenousformulation showed no significant benefit. More research is needed in this area to expound on these results.


60/90


SAMe

Adverse effects

FlatulenceMild GI complaintsDry mouthHeadacheInsomniaCautions

Bipolar disorder: may cause hypomania

InteractionsTricyclic antidepressantsSelective serotonin reuptake inhibitors (SSRIs)Monoamine oxidase inhibitors (MAOIs)LevodopaDosing

Depression: 400-1600mg PO QD (200-400mg IV/IM QD)Osteoarthritis: 200mg PO TID (400mg IV QD)

Fibromyalgia: 800mg PO QDSAMe is generally very well tolerated. Unlike many other dietary supplements, SAMe has been studied in clinical trials lastingup to 2 years in duration and in over 22,000 people cumulatively with few serious side effects. The most common complaintsin people taking SAMe include flatulence, mild gastrointestinal complaints such as nausea, vomiting, diarrhea, andconstipation, dry mouth, headache, and insomnia. SAMe should be used with caution in patients with bipolar disorderhowever due to reports of hypomania and one case of conversion to mania.


61/90


SAMe

Due to the serotonergic effect of SAMe, there is the potential for serotonergic symptoms when combined with othermedications 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 totreat 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.


62/90


St. Johns Wort

Common use

DepressionStandardization

Hypericin 0.3%Hyperforin 3-5%Mechanism of action

Inhibits reuptake of serotonin, norepinephrine, dopamineGABA effectsInduces 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 compulsivedisorder, 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. Researchersused to think hypericin was the active ingredient, but now it is thought that the antidepressant activity is most likely due tohyperforin. 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 gamma-butyric 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 decreasedserum levels of many other medications. Hyperforin also induces CYP2C9 and 1A2 to a lesser degree. There appears to beno clinically significant effect on CYP2D6. Hypericin content is largely responsible for the photosensitivity associa

Date post:	04-Apr-2018
Category:	Documents
Upload:	geekay79
View:	220 times
Download:	0 times

Module 20 - Complementary and Alternative Medicine

Documents