COMMON HERBS AND SUPPLEMENTS:

A REVIEW OF SAFETY AND EFFICACY

Marina Shkayeva, PharmD Natural Standard, PGY-1 Pharmacy Resident

Natural Standard: Webinar Disclaimer

This webinar is intended for informational purposes only, and should not be interpreted as specific medical advice. A qualified healthcare provider should be consulted before making decisions about therapies and/or health conditions. While some complementary and alternative techniques have been studied scientifically, high quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by recognized professional organizations that adhere to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare providers. Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The following webinar is designed to provide historical background and an overview of clinically oriented research, and neither advocates for or against the use of a particular therapy.

Objectives

Examine indications, dosage, adverse effects, and interactions for the following supplements:
Acai,

coenzyme Q10 (CoQ10), fish oil, red yeast rice, ginkgo, echinacea, black cohosh, blue cohosh DHEA, kava, ginseng, garlic, peppermint, saw palmetto, St. John's wort, valerian

Natural Standard evidence-based validated grading rationale

Aa

An antioxidant berry from tropical Central and South America

Reddish-purple fruit, tastes like a blend of berry and chocolate Variety of aa products are available:
Juices,

powders, tablets, and capsules

Natural Standard: Dosing Disclaimer

The following doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Aa
INDICATIONS

DOSE

Evidence grade B:
Antioxidant

Suggested:
1

Evidence grade C:
Metabolic

syndrome

oz. of powder mixed with 10-12 oz. of water once or twice daily Freeze-dried aa in capsules or tablets at 1-2g daily

Natural Standard: Safety Disclaimer

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Natural Standard: Interactions Disclaimer

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Aa
ADVERSE EFFECTS

INTERACTIONS

Likely safe in food amounts

May reduce blood sugar levels, caution with diabetic agents May block the effects of immunosuppressant agents May increase potassium levels

Coenzyme Q10

CoQ10, ubiquinone
Endogenously produced, fat-soluble A co-factor in oxidative respiration for the Krebs cycle and the electron transport chain

Levels decrease with age & in patients with:

Cardiovascular disease, muscular dystrophy, Parkinson's disease, cancer, diabetes, human immunodeficiency virus (HIV)

Standard therapy for congestive heart failure in Europe, Russia and Japan

Coenzyme Q10
INDICATIONS

DOSE

Evidence grade A

CoQ10 deficiency

50-1,200mg of CoQ10 daily

Evidence grade B

Hypertension

Evidence grade C

Alzheimer's disease Cancer Chronic fatigue syndrome Migraine

Coenzyme Q10
ADVERSE EFFECTS

INTERACTIONS

Mild, brief, and selfresolving:

Nausea/vomiting/diarrhea (N/V/D), stomach upset, heartburn, appetite loss Pruritis, rash Insomnia, headache, dizziness, irritability, fatigue Flu-like symptoms

May reduce warfarins effectiveness May deplete CoQ10 levels:

Diabetes drugs Tricyclic antidepressants Antipsychotics Statins Alzheimer's drugs Anticancer drugs Immune system-altering drugs Diuretics, beta-blockers

Omega-3 Fatty Acids (Fish Oil)

Inuit people of Greenland have low occurrence of heart disease

Diet high in fat and rich in omega-3 fatty acids

Essential fatty acids in diet are omega-3 and omega-6 fatty acids

Omega-3 and Omega-6 compete for same receptors Omega-3: decreases inflammation Omega-6: promotes inflammation

Optimal ratio of omega-6:omega-3 fatty acids is 4:1

American diet 20:1 up to 30:1

Omega-3 Fatty Acids (Fish Oil)

OMEGA-3 FATTY ACIDS

OMEGA-6 FATTY ACIDS

Alpha-linolenic acid (ALA)

Green vegetables, canola oil, nuts, soybeans <10% converted into eicosapentaenoic acid (EPA) & docosahexaenoic acid (DHA) Anchovy, salmon, sardine, seal blubber, sturgeon, trout, tuna, and whale blubber

Linoleic acid
Palm,

rapeseed, and sunflower oils

EPA and DHA:

Omega-3 Fatty Acids (Fish Oil)

INDICATIONS

DOSAGE

Evidence grade A
Coronary

heart disease Hyperlipidemia Hypertension Rheumatoid arthritis Secondary cardiovascular disease prevention

Americans consume 1.6g of omega-3 fatty acids daily

~90% from ALA, and ~10% from EPA and DHA

1g capsules of omega-3 fatty acids 3g of omega-3 fatty acids from fish daily

Clinical trials:

GRAS:

Omega-3 Fatty Acids (Fish Oil)

ADVERSE EFFECTS

INTERACTIONS

N/V/D, decreased appetite, constipation, steatorrhea, fish burp Rare:

May increase bleeding with:

Aspirin Anticoagulants

Mild elevations in liver function tests Mania in patients with bipolar disorder or major depression. Restlessness and formication

Anti-platelet

drugs Non-steroidal antiinflammatory drugs (NSAIDs)

Red Yeast Rice

Red yeast rice (RYR) is the product of yeast (Monascus purpureus) grown on rice, popular in Asian countries Sold over the counter as Cholestin (Pharmanex, Inc.) Contains monacolins, which inhibit cholesterol synthesis

Monacolin K, has the same chemical structure as the drugs lovastatin and mevinolin

RYR may lead to a 10-33% reduction in low-density lipoprotein (LDL) levels

RYR: A Federal Case

1998: Cholestin (Pharmanex, Inc.) taken off the market due to monacolin K or lovastatin content, an active ingredient of Mevacor (Merck & Co.) Now: Cholestin can be purchased in the United States from Pharmanex or specific dealers Pharmanex claim: Cholestin contains 12 natural substances acting together to "support healthy cholesterol levels."

Red Yeast Rice

INDICATIONS

DOSAGE

Evidence grade A:
Hyperlipidemia

1,200mg of RYR capsules two times daily

Evidence grade C:
Coronary Diabetes

heart disease

Red Yeast Rice

ADVERSE EFFECTS

INTERACTIONS

Limited evidence on the side effects of red yeast Like lovastatin:

Additive effects with drugs that increase bleeding Like lovastatin:

Alcohol

Heartburn, gas, bloating Muscle pain or damage Dizziness, asthma, and kidney problems

Avoid in people with liver disease

and other drugs toxic to the liver should be avoided

Garlic

A culinary herb used for cardiovascular disease and cancer

Use of garlic might date back to ancient Greek medicine and traditional Chinese healers Has a sulfur compound alliin, which makes allicin when the bulb is crushed or ground

Garlic
INDICATIONS

DOSAGE

Evidence grade A
Hyperlipidemia
Hypertension

World Health Organization (WHO) recommends daily:

2-5g fresh garlic (2-5 mg of allicin) 2-5mg oil 300-1,000 mg of extract

Evidence grade B
Cardiovascular

disease

risk

Garlic
ADVERSE EFFECTS

INTERACTIONS

Allergies: Liliaceae family

Hyacinth, tulip, onion, leek, and chives

Increased bleeding risk with:

Aspirin Anticoagulants

Common: Bad breath, body odor Rare: Dizziness, anorexia, N/V/D, belching, heartburn, constipation, flushing, tachycardia, insomnia, headache, fever, chills Serious: Bleeding

Anti-platelet
NSAIDs

drugs

Ginseng

Species of the genus Panax of the Araliaceae family

Most common are American and Asian ginseng

Ginsenosides are the active components of ginseng

Quantity depends on species and growth conditions

In traditional Chinese medicine used for:

Increasing appetite, blood volume, strength Enhancing physical performance and memory Reducing fatigue and stress

Ginseng
INDICATIONS

DOSAGE

Evidence grade B
Hyperglycemia
Immune

system enhancement Mental performance

100-200mg daily German pharmacopeia (DAB 10):

1-2g

of dried ginseng root or 20-30mg ginsenosides

Ginseng
ADVERSE EFFECTS

INTERACTIONS

May cause insomnia, rash, bleeding, gastrointestinal (GI) effects, hypoglycemia High doses: light-sensitizing effect Caution in patients with mental health disorders and arrhythmias

Increased bleeding risk with:

Aspirin Anticoagulants Non-steroidal

antiinflammatory drugs

Ginkgo

Ginkgo biloba has been used for thousands of years and is a top selling herb in the United States Traditional Chinese Medicine (TCM):

Pulmonary diseases, circulatory disorders, memory loss, and skin lesions

Europe and the United States:

Dementia,

memory enhancement, and claudication Not GRAS

Ginkgo
INDICATIONS

DOSE

Evidence grade A
Claudication

80-240mg of a 50:1 standardized leaf extract daily 30-40mg of extract prepared as a tea Effects may take 4-6 weeks to appear

(peripheral vascular disease) Dementia

Ginkgo
ADVERSE EFFECTS

INTERACTIONS

Cross-sensitivity with urushiols

Mango rind, poison sumac, poison ivy, poison oak, cashews

May increase bleeding risk with:

Aspirin Anticoagulants Anti-platelet drugs NSAIDs

Well tolerated at suggested doses up to six months Headache, nausea, intestinal complaints, bleeding May be unsafe in children May increase the risk of stroke

May affect insulin and blood sugar levels

Echinacea

Echinacea species are of the Asteraceae family and originated from North America In Europe and the United States for upper respiratory tract infections (URIs)
~10% of the dietary supplement market

Many positive trials published before 2001

Limited

quality or combination products

Echinacea
INDICATIONS

DOSAGE

Evidence grade B

URI or common cold:

URI treatment (adults)

500-1,000mg three times daily

Evidence grade C
Cancer Genital herpes Immune system stimulation URI prevention URI treatment (children)

Tea: two teaspoons (4g) of herb in one cup of water daily

Taken for up to a week

Echinacea
ADVERSE EFFECTS

INTERACTIONS

Cross-sensitivity to the Asteraceae family

Including ragweed, chrysanthemum, marigold, and daisy

Mildly interact with cytochrome P450 enzymes

Well tolerated and few adverse effects

GI effects and rashes

Question

Which of the following herbs increase the risk of bleeding?

A.

Coenzyme Q10 B. Red yeast rice C. Garlic D. Ginseng E. Ginkgo F. Echinacea

Question

Which of the following herbs increase the risk of bleeding?

A.

Coenzyme Q10 B. Red yeast rice

C.

Garlic D. Ginseng E. Ginkgo

F.

Echinacea

Summary
SUPPLEMENT
Acai

INDICATION
Anti-oxidant

ADVERSE REACTION
Generally safe

Coenzyme Q10
Omega-3 fatty acids Red yeast rice

Deficiency, HTN
Elevated triglycerides Hyperlipidemia

Mild GI
Mild GI, fish burp GI, muscle pain

Garlic
Ginseng

Hyperlipidemia, HTN
Mental performance, immune stimulation

Bad odor, bleeding

Insomnia, bleeding

Ginkgo
Echinacea

Dementia
Immune stimulation

Bleeding, hypoglycemia
Allergic reactions

Black Cohosh

Alternative to hormonal therapy for menopause:

Hot

flashes, mood disturbances, sweating, palpitations, vaginal dryness

Controlled trials and case series:

Improved

menopausal symptoms for up to six months Lacking safety and efficacy data after six months

Controversy: is there an effect on estrogen receptors?

Black Cohosh
INDICATIONS

DOSAGE

Evidence grade C:
Arthritis

Traditional doses
1-2g

pain Breast cancer Infertility Menopausal symptoms Migraine (menstrual)

three times a day

Studies, menopausal symptoms

20-40mg

Remifemin tablets twice a day for 12 weeks

Black Cohosh
ADVERSE EFFECTS

INTERACTIONS

Not GRAS High doses:

Estrogen-like effect is debated May interact with

Frontal headache, dizziness, visual disturbances GI effects, bone mass loss, irregular heartbeat, low blood pressure, muscle damage

Rare:

Tamoxifen Raloxifine

Unclear if safe in hormonesensitive conditions

Caution with other hypotensive agents, for additive effects

Blue Cohosh (Do Not Confuse)

INDICATIONS

SAFETY

Traditionally:

Overdose:

To stimulate and ease labor Pelvic inflammatory disease, endometriosis, erratic menstruation Increased uterine contractions

Theory:

Nausea, vomiting, headache, thirst, dilated pupils, muscle weakness, tachycardia, cardiovascular collapse, and convulsions

In vitro and in vivo:

Sufficient data is lacking

Cases of neonatal myocardial toxicity and newborn myocardial infarction Sufficient data is lacking

DHEA (Dehydroepiandrosterone)

An endogenous hormone from the adrenal gland

Precursor

to androgens and estrogens

DHEA levels in the body begin to decrease after age 30, and reported to be low in people with:
Anorexia,

end-stage kidney disease, type 2 diabetes, AIDS, adrenal insufficiency, and in the critically ill

DHEA levels may be depleted by drugs

DHEA
INDICATIONS

DOSAGE

Evidence grade B:

Adrenal insufficiency Depression Obesity Systemic lupus erythematosus

Common
25-200mg

daily up to

one year

Evidence grade D:

Depression in HIV/AIDS
200-500mg

Memory Muscle strength

daily

DHEA
ADVERSE EFFECTS

INTERACTIONS

Uncommon in recommended doses Fatigue, headache, acne, tachycardia, increased glucose Avoid in arrhythmias, hypercoagulability, liver disease

May inhibit cytochrome P450 enzymes Decrease DHEA concentrations:

Carbamazepine and phenytoin Insulin Corticosteroids Opiates Danazol

Kava

Kava beverages, from roots of the shrub Piper methysticum

Traditionally

used in the South Pacific Pleasant mild psychoactive effects, similar to alcoholic beverages

Preliminary evidence:
Efficacy

may be equivalent to benzodiazepines

Was used as an anxiolytic in Europe and USA

Kava
INDICATIONS

DOSAGE

Evidence grade A:
Anxiety

Evidence grade C:
Insomnia Parkinson's

Start low and increase over time 50-280mg kava lactones at bedtime 60-120mg of kavapyrones daily High dose in studies

disease

800mg daily of kava extract (short term)

Kava
ADVERSE EFFECTS

INTERACTIONS (Theoretical)

Not GRAS anymore

Cases of liver toxicity and liver failure May cause kidney damage

Natural medicine experts:

Kava is safe at recommended doses

Acetaminophen Additive sedation with alcohol Worsen side effects of drugs blocking dopamine (e.g. Haldol) Additive with monoamine oxidase inhibitors Prolong effects of anesthesia

No clear conclusion

Stop kava 2-3 weeks before surgery

Valerian

Valeriana officinalis: Valium of the 19th Century"

Restlessness, insomnia, hypnotic, sedative, antispasmodic

MOA: increase synaptasomal gamma-aminobutyric acid (GABA) concentrations May contain up to 150 compounds, not all of which have been investigated
Known compounds: valepotriates, volatile oils, kessanes, valerenal, valeranone, and valerenic acid Bad smell: isovaleric acid Cat attractant: actinidine

Valerian
INDICATIONS

DOSAGE

Evidence grade C:
Anxiety
Depression Insomnia Menopausal Sedation

Studies:
400-900mg

of extract

at bedtime 300-1,800mg capsule symptoms

Historically as tea
1.5-3g

root

Valerian
ADVERSE EFFECTS

INTERACTIONS

GRAS list Well tolerated for 4-6 weeks in recommended doses Valerian withdrawal
Confusion, delirium, and tachycardia Chronic use: insomnia

Additive sedation effects with benzodiazepines, barbiturates, narcotics, anti-depressants, alcohol May have additive effects with betablockers

Saw Palmetto

Traditionally used by Native Americans

Serenoa repens used in Europe and USA for benign prostatic hypertrophy (BPH) Many studies: superior to placebo for BPH symptoms However:
Trials were short(1-6 months) and had small sample sizes Did not use standardized outcomes measurements

Saw Palmetto
INDICATIONS

DOSAGE

Evidence grade A:

Benign prostatic hypertrophy

BPH studies:
320mg

daily

Evidence grade C

Androgenetic alopecia Hypotonic neurogenic bladder Prostate cancer Prostatitis

Reports:
160mg

daily may be as effective as 160mg twice a day

Saw Palmetto
ADVERSE EFFECTS

INTERACTIONS

Common:
Gastrointestinal

Increases bleeding risk with:

effects, bad breath, constipation

Aspirin Anticoagulants Anti-platelet drugs NSAIDs

Should not be taken with drugs that affect androgen levels:

Finasteride (Proscar) Flutamide (Eulexin)

Peppermint

Mentha x piperita is a hybrid of spearmint and water mint

Products: peppermint oil, menthol GRAS in food amounts

MOA: reduces gastrointestinal smooth muscle motility, perhaps by calcium channel antagonism Food and pharmaceutical industries use for cooling property, scent, and flavor

Peppermint
INDICATIONS

DOSAGE

Evidence grade A

Irritable bowel syndrome (IBS)

Recommend not using peppermint oil topically more than 3-4 times daily Intestinal/digestion disorders:

Evidence grade B
Antispasmodic Breast tenderness Dyspepsia Headache (topical)

0.2-0.4mL of peppermint oil in enteric-coated capsules or liquid preparations TID 2-10mg of peppermint oil in a lozenge

For sore throat

Peppermint
ADVERSE EFFECTS

INTERACTIONS

Topically: allergic reactions, mouth ulcers, chemical burn Orally: dizziness, heartburn, slow heart rate, dental caries, gingivitis, or muscle tremor Use cautiously in hiatal hernia, achlorhydria, gastroesophageal reflux disease

May moderately inhibit CYP 1A2, 2E, and 3A4 May cause synergistic effects with anti-hypertensives and anti-hyperglycemics Menthol may enhance absorption of steroids, salicylates

St. Johns Wort

Extracts of Hypericum perforatum is not on GRAS list Treatment of mild-moderate major depression:
More

effective than placebo and equally effective as tricyclic antidepressant drugs for 1-3 months Controversy about the trials, problems in design

Serious interactions with prescription drugs, herbs, and supplements

St. Johns Wort

INDICATIONS

DOSAGE

Evidence grade A

Depression

Trials:
0.17-2.7mg

Evidence grade B

of hypericin daily of St. John's wort extract daily

Somatoform disorders
150-1,800mg

Evidence grade D

Depressive disorder Human immunodeficiency virus (HIV)

St. Johns Wort

ADVERSE EFFECTS

INTERACTIONS

Well tolerated at recommended doses for up to 1-3 months Common (1-3%):

CYP 450 inducer

GI upset, fatigue, sedation, anxiety, sexual dysfunction, dizziness, headache, dry mouth

Studies had small populations, bias, variable duration and dose Carbamazepine, cyclosporine, midazolam, simvastatin, warfarin FDA: patients on medications for HIV should not take St. John's wort

May cause suicidal and homicidal thoughts

Antidepressants: serotonin syndrome and mania

Summary
SUPPLEMENT
Black cohosh **Blue cohosh DHEA Kava Valerian Saw palmetto Peppermint St. Johns Wort

INDICATION
Menopausal symptoms Stimulate labor Adrenal insufficiency Anxiety Anxiety, insomnia BPH Irritable bowel syndrome Depression

ADVERSE EFFECTS
GI effects, bradycardia, hypotension Toxic to mother & fetus Fatigue, tachycardia Liver toxicity Sedation Bleeding Dyspepsia, topical irritation GI effects, anxiety

Conclusions

Many herbs and supplements lack quality studies

Supplements/herbs are generally well tolerated in recommended doses with no contraindications

Be aware of interactions and safety information that is available

References
Information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com)
Dietary Supplements. Food and Drug Administration. October 14, 2012. <http://www.fda.gov/food/dietarysupplements/default.htm> Kimpel , Paul. The Cholestin Case: Drug vs. Supplements. Interactive Media Lab at University of Florida. October 12, 2012. <http://iml.jou.ufl.edu/projects/spring2000/kimpel/cholestin.html>