Dietary Supplements

• A product intended to supplement the diet
• Not considered a food or a drug

• Definition of dietary supplement
• Cannot refer to any specific disease. "Not evaluated by FDA, etc"
• Remove product only when hazardous
• Office of Dietary Supplements
• No claims of efficacy. Only structure/fxn claims.

• Cannot name specific disease of class of diseases on label
• Name of product cannot sound like a disease (e.g. hepatacure, raynaudin)
• Citation of a title referring to a disease may be ok as long as not bolded on label.
• May not use "disease" or "diseased"
• May not use class names (antibiotic, analgesic)

• antacid
• laxative
• antigas
• stool softener
• stimulant
• nighttime sleep-aid

• Maintains healthy blood sugar (structure/fxn)
• Controls blood sugar in persons with insufficient insulin (disease)
• Alzheimer's (disease)
• Support for menopausal women (str/fxn)
• Mild memory problems assoc with aging (str/fxn)
• Maintains healthy lungs in smokers (disease)
• Osteoporosis (disease)
• Healthy lung function, smoking alternative (str/fxn)
• Maintains cholesterol within normal range (str/fxn)
• Lowers cholesterol (disease)

• Name of product
• Supplement Facts panel (suggested serving size, net quantity of ingredients, dietary supplements and their RDAs if known, herbs must be identified by common plant name and what part of plant was used)

• patent autonomy
• patient use
• cheaper than rx meds
• profit to be made?

• Fear of legal liability
• Lack of reputable manufacturers
• Absence of FDA approval
• Difficulty identifying product content
• Reviewing hundreds of products and indications
• Health care provider concerns

• They are like the FDA in Germany
• Established Commission E in 1978 to evaluate safety and efficacy of herbs
• Published 380 monographs of herbs (like a "textbook", but it hasn't been updated since the mid-90s)

• Borage
• Calamus
• Coltsfoot
• Comfrey
• Life root
• Sassafras
• Butterbur
• Chaparral
• Germander
• Pennyroyal oil
• Heliotrope
• Kava
• Licorice
• Ma Huang
• Pokeroot
• Willow bark
• Jin Bu Huan
• Stephania and Magnolia
• Germanium
• Lobelia
• L-tryptophan
• Phenylalanine
• Yohimbe

• Aconite
• Bitter orange
• Chapparal
• Colloidal Silver
• Coltsfoot
• Comfrey
• Country mallow
• Germanium
• Greater Celadine
• Kava
• Lobelia
• Yohimbe

• Dietary Supplement Verification Program
• Developed by USP
• Volunteer-driven, not-for-profit, non-governmental program

• Establish quality standards for dietary supplements
• Audit mfg facilities for GMP compliance
• Product testing (labeling, contamination, content, integrity of ingredients, dissolution, purity, safe manufacturing)

• Do not address nutritional claims, safety or efficacy
• Only check on mfr and make sure products are clean

• Companies must comply with this rule
• Mfrs must evaluate for:
• - identity
• - purity
• - strength
• - composition

2-3 weeks prior

With most of them, it makes the other drug less effective

(Antidepressants, Anti-retrovirals, Barbs, Clopidogrel, Cyclosporine, Digoxin, Irinotecan and imatinib, Methadone, Omeprazole, OCs, Statins, Tacrolimus, Theophylline, Triptans, Verapamil, Warfarin)

• Efficacy - well-controlled clinical studies
• Effectiveness - real-world populations

• several ingredients studied
• lack of standardization
• adulterated or misbranded
• foreign language only
• small sample size
• poorly defined inclusion/exclusion criteria
• short study duration

• premenstrual symptoms
• painful menstruation
• hot flashes

• pregnancy
• don't take for longer than 6 months
• estrogen receptor positive breast cancer (maybe)
• liver disease

• decrease in cisplatin
• hepatotoxic drugs??? CYP 2D6

• intestinal probs, weight gain, nausea
• liver toxicity (monitor LFTs)
• Autoimmune hepatitis
• dizziness, HA, stiffness, trembling limbs (large doses)

prevention of recurrent UTIs

• BPH
• urinary obstruction
• nephrolithiasis
• allergies/asthma (d/t high salicylic acid)
• GERD/ulcers
• (d/c 2 weeks prior to surgery)

• Vitamin B12 (Increased absorption)
• Warfarin (increased INR)
• CYP 2D6 meds (phenytoin, warfarin)
• Do not take with NSAIDS

• N/V/D
• nephrolithiasis

• Strengthens resistance to URT infx
• Boosts immune system to help fight off infx

• TB, leukosis, collagenosis, MS, AIDS, HIV infx, AI diseases (theoretically - thought to make them worse)
• allergies to ragweed
• pregnancy/lactation
• 8 weeks of use max
• asthma??

• Immunosuppressants?
• Inhibits CYP 1A2
• Induces and inhibits CYP 3A4

• N/V
• allergic rxns (anaphylaxis, angioedema, urticaria)
• acute asthma
• leukopenia
• may interfere with male fertility

Prophylaxis of migraines

• pregnancy/lactation
• children

• Anticoagulants
• CYP 1A2, 2C9, 2C19, 3A4

• Mucosal and gastric irritation
• Post-feverfew syndrome - includes anxiety, HA, insomnia, m and joint stiffness - may be d/t release of serotonin

• (not evaluated by German Commission E)
• HTN
• hyperlipidemia
• Mental health (bipolar, psychosis, depression)
• Anticoagulant
• coronary heart disease
• stroke

• seafood allergy
• bipolar disorder
• bleeding
• cardiac disease
• depression
• diabetes
• HTN
• immunodeficiency

• Anticoagulants/Antiplatelets/Thrombolytics (increase bleeding)
• Antihypertensives (may reduce BP more)
• Xenical, Alli, Orlistat (decrease abs of fish oil - separate by 2 hours)

• Bleeding
• Ecchymosis
• Epistaxis
• Hypervitaminosis A
• Hypervitaminosis D
• Rash
• Dyspepsia
• Eructation (burping)
• N/V/D
• Halitosis
• Dysgeusia (taste perversion)

It may help to freeze the capsules or use enteric coated capsules.

• (Not evaluated by German Commission E)
• Constipation
• Diarrhea
• Diabetes
• Menopause
• HTN
• Hyperlipidemia
• CAD

• Anticoagulants
• Antidiabetic agents (could cause hypoglycemia)
• Estrogens
• Decreased absorption of oral drugs (d/t fiber content)

• Bloating
• Flatulence
• Abdominal pain
• Diarrhea
• Constipation
• Dyspepsia
• Nausea
• Allergic Reactions

• hyperlipoproteinemia
• arteriosclerosis

(possibly anticancer effects - may inhibit different chemical carcinogens)

Allicin

• Diabetes (increased insulin - hypoglycemic effects)
• Pregnancy/lactation/children
• Peptic ulcers/GERD
• D/C 2 weeks prior to surgery (it increases bleeding)

• Anticoagulants (esp warfarin!)
• Protease inhibitors may be decreased (saquinavir, ritonavir)
• NNRTIs may be decreased (nevirapine, efavirenz)
• Inhibits CYP 2D6, 2C9, 2C19, 3A4, 2E1
• Amphotericin B (increases its activity vs. cryptococcus neoformans)
• Diabetic agents (hypoglycemia)
• Antihypertensives (hypotension)
• Protects against drug toxicities from doxorubicin, APAP, methotrexate, fluorouracil

• GI discomfort
• sweating
• dizziness, lightheadedness
• allergic rxns: anaphylaxis, urticaria
• bleeding, menorrhagia
• smelling like garlic

• venous conditions (alternative to compression stockings)
• eczema
• leg pains
• hemorrhoids
• phlebitis
• menstruation

• Renal (nephropathy)
• Hepatic (liver injury case)
• Pediatric (poisonings reported)
• Pregnancy/lactation
• Diabetes (hypoglycemia)
• GI irritation
• Latex allergy (cross sensitivity)

• Anticoagulants/antiplatelets
• Antidiabetic drugs (hypoglycemia)
• Lithium (d/t diuretic effect of horse chestnut seed)

• GI irritation, pruritis, giddiness, HA
• Toxic nephropathy
• Bleeding/bruising

Symptoms of poisoning: muscle twitching, weakness, loss of coordination, dilated pupils, vomiting, diarrhea, depression, paralysis, stupor

• Cerebral circulatory disturbances
• Peripheral arterial circulatory disturbances
• (maybe for memory? - but not actually an indication)

• Epilepsy (ginkgotoxin may cause neurotoxicity and seizures)
• Bleeding disorders (d/c 2 weeks prior to surgery)
• Diabetes (hypoglycemia)
• Infertility (male and female)

• Antiplatelets, NSAIDS, Warfarin
• Aminoglycosides (increased ototoxicity)
• Thiazides (increased BP)
• Trazodone (coma)
• Seizure threshold lowering drugs
• Anticonvulsants
• Antidiabetic drugs (hypoglycemia)
• May mildly affect CYP 1A2, 2C9, 2C19, 2D6, 3A4 (efavirenz)

• GI disturbances
• HA, dizziness, vertigo
• Allergic skin rxns
• spontaneous bleeding, intracerebral bleeding, spontaneous hyphema (bleeding/hemorrhage in eye)
• Toxicity: seizures and unconsciousness - death

• "adaptogen" for increasing resistance to environmental stress
• lassitude and debility
• lack of energy
• inability to concentrate
• convalescence

• HTN
• emotional and psychological imbalances
• HA
• heart palpitations
• insomnia
• asthma
• inflammation
• infections
• pregnancy/lactation
• children
• hx of bleeding
• d/c 2 weeks prior to surgery
• diabetes (hypoglycemia)
• schizophrenia (may be exacerbated)
• May stimulate breast cancer cells

• MAOIs (phenelzine)
• Warfarin (INR decreased)
• Stimulants
• Alcohol (excretion increased)
• Hypoglycemics
• ?hormonal therapy
• ?antihypertensives
• ?cardiac meds
• ?asthma meds
• Inhibits CYP 2D6 (amitriptyline and fluoxetine)
• May interfere with immunosuppressants

• Diffuse mammary nodularity
• Vaginal bleeding
• Gynecomastia
• HTN
• Hypoglycemia
• Nervousness, excitation, insomnia
• Inability to concentrate
• Palpitations
• Diarrhea

• Chronic inflammatory liver conditions
• Cirrhosis

• pregnancy
• allergy to ragweed, chrysanthemums
• hormone sensitive cancers

• Inhibits CYP 2C9, 3A4
• No intx with indinavir

• Diarrhea, nausea, dyspepsia, flatulence
• Allergic rxns, rash

BPH

• pregnancy
• children
• d/c 2 weeks prior to surgery

• Anticoagulants?
• Contraceptive drugs or hormone replacement therapy? (antiestrogenic effects)

• Intraoperative hemorrhage
• HA
• Stomach upset
• Acute hepatitis and pancreatitis

• Anxiety
• Depression

• Fair-skinned persons
• Pregnancy/lactation (abortofacent)
• Psychiatric conditions (may exacerbate bipolar, schizophrenia)
• Alzheimer's Disease (may induce psychosis)
• Hypothyroidism
• Anesthesia (may cause CV collapse)
• Surgical procedures (d/c 2 wk prior)
• Infertility
• (No negative influence on general performance, ability to operate car/heavy machinery)

• CYP 1A2, 2C9, 2C19, 3A4
• (decreases efficacy of the other drug unless otherwise specified)
• Antidepressants
• Anti-retrovirals
• Barbs
• Clopidogrel (increased efficacy)
• Cyclosporine
• Digoxin
• Irinotecan and Imatinib
• Methadone
• Methylphenidate
• Omeprazole
• OCs
• Phenytoin
• Statins
• Tacrolimus
• Theophlline
• Triptans?
• Verapamil
• Warfarin (decreased INR)

Tyramine containing foods (possibly)

• Photodermatitis/phototoxicity
• Nausea, constipation, GI distress
• Allergic rxns
• tiredness, restlessness, sleep disturbances
• mania or hypomania
• elevated TSH
• elevated BP
• male/female infertility

• Restlessness
• Nervous disturbance of sleep

• Similar to Benzos, Barbs, Opiates
• Caution while driving or performing tasks requiring alertness and coordination

• CNS depressants (may potentiate the sedative effect of barbs, benzos, opiates, alcohol, other sedatives)
• Inhibits CYP 3A4
• Sedatives
• Anxiolytics
• MAOIs
• Alcohol
• Antidepressants

• HA
• Hangover
• Excitability
• Insomnia
• Uneasiness
• Cardiac disturbances
• Hepatotoxicity
• Toxicity: ataxia, hypothermia, hallucinations, increased muscle relaxation

• osteoarthritis
• improves cartilage
• inhibits breakdown of existing cartilage

• Glucosamine:
• Antidiabetic agents (hypoglycemia)
• May induce resistance to antimitotic chemotherapy (etopside, doxorubicin)
• Warfarin?

• Chondroitin:
• Interacts with heparin/warfarin

• G: Shellfish
• C: Beef or shark

diabetes, asthma, bleeding disorders

• (not evaluated by German Comission E)
• CHF
• HTN
• Stable angina
• Ventricular arrhythmias
• Cancer
• Heart surgery
• Peridontal disease

• Biliary obstruction
• Diabetes (hypoglycemia)
• Hepatic insufficiency
• Renal insufficiency
• Hyper and hypotension

• Statins may lower the plasma conc of CoQ10
• Oral hypoglycemic agents potentially inhibit effects of exogenous admin
• Doxorubicin toxicity may be increased
• Antihypertensives (additive effect)
• Warfarin (CoQ10 structurally related to Vitamin K, so may have coagulant effects)

• rash
• GI disturbances
• Elevations of LFTs

(similar to Ramelteon)

Orphan drug status: Tx of circadian rhythm sleep disorders in blind ppl with no light perception

Non-approved indications: jet lag, insomnia, depression, cancer

• Pregnancy
• May aggravate depressive symptoms
• May increase incidence of seizures
• Diabetes (hyperglycemia)
• HTN (exacerbated)

• SSRIs (may increase serum conc of melatonin)
• Other sedatives (may exacerbate effect)
• Anticoagulants (increased effect)
• Contraceptives (efficacy of melatonin could be increased)
• Immunosuppressants
• Caffeine (could decrease efficacy of melatonin)
• Antidiabetic agents (may be less effective)
• Verapamil (increases excretion of melatonin)

• Drowsiness, daytime fatigue, HA, dizziness, transient depression
• Long-term SEs unknown

• The FDA does not regulate the standardization, efficacy, safety, drug interactions
• Tell them what we do know of the product from the available literature

Potential liability