Health Issues II - Unit 2: Current State of Alternative Therapy in the U.S & Top Selling Herbal Therapies - Dr. Long

Safety Issues in the US: <_____% of adverse effects are reported.

1

During the last portion of the 20th century, renewed lay interest in natural products has increased due to the following reasons (4):

1) The lay public's discovery of the utility of whole plant drugs or herbs. 2) Dissatisfaction with the efficacy, side effects, or costs of modern medicines 3) An overall increase in interest in organic or "natural" foods and products 4) Ease and availability of information (television, internet)

What is the dose of cranberries for recurrent UTI prevention?

300 mL of juice daily

What is the clinical data regarding elderberries?

A few small, preliminary studies have investigated the effectiveness of elderberry in some viral infections. Early data seem to indicated that if taken early in the infection, elderberry may lessen the signs and symptoms of flu, including some studies specifically targeting the H1N1 (swine) flu.

What are the constituents of elderberries?

A series of flavinoid glycosides variously identified as sambuculin or anthocyanidins Cyanogenic glycosides (sambunigrine) Specific lectins

What are the constituents of ashwagandha?

A series of triterpene lactones called the withanolides.

Both THC and CBD have been recommended for treatment for the following, but little to no evidence supports their use for these conditions:

ALS, autism, cerebral palsy, cystic fibrosis, migraine, psoriasis, Alzheimer's dementia, arthritis, Crohn's disease, hepatitis C, Parkinson's disease, or PTSD.

What are the side effects, toxicities, and warnings of saw palmetto?

Abdominal and back pain Constipation or diarrhea Decreased libido or impotence Dysuria and urinary retention Headache Hypertension Nausea Take with meals to minimize GI upset

What receptors does THC act on?

Agonist at endogenous CB1 and CB2 receptors (Endogenous signalling agents for CB receptors are arachidonic acid derivatives: arachidonylethanolamide/anandamide or 2-arachidonoylglycerol)

What are the demonstrated actions of wheat?

Agropyrene is possibly effective as an antibiotic and apigenin may exhibit anti-oxidant/anti-inflammatory activity. However, very little data on the effectiveness of wheat grass exists.

What are the constituents of echinacea?

Alkylamides, including chicoric acid, caffeic acid, and high molecular weight polysaccharides

What are the side effects, toxicities, and warnings of echinacea?

Allergic reactions, including anaphylaxis. May inhibit 3A4 and 1A2 pathways. One study indicated a potential for causing infertility, especially in males, perhaps through interfering with spermatozoa enzymes.

What are the side effects, toxicities, and warnings of barley grass?

Allergies in sensitive individuals; may also lower glucose, causing hypoglycemic reactions.

What are the constituents of garlic?

Alliin — this component is converted via the enzyme alliinase to allicin. Allicin is thought to be responsible for the majority of garlic's beneficial effects. It also imparts the characteristic odor of garlic. Ajoene is another metabolic product that also possesses pharmacologic activity. Other constituents — methylallyltrisulphide, Vitamins A, B, and C, trace minerals

What are the demonstrated actions of aloe?

Aloin produces a stimulant laxative effect accompanied with electrolyte loss The gel has been reported to decrease signs and symptoms of inflammation and possibly promote wound healing Early and sparse evidence might support cytotoxic/anti-tumor actions

What are the demonstrated actions of ashwagandha?

Animal data indicate that ashwagandha may possess anti-inflammatory/analgesic activity, anti-proliferative/apoptotic anti-cancer effects, immunomodulatory, antioxidant, anxiolytic, thyroid-modulating, and memory-improving effects. Many one-study papers have described numerous other actions, but these have not been confirmed by additional research (male infertility, respiration, hypotensive, anti-convulsant).

What are the side effects of cannabinoids regarding CBD?

Anorexia, sleep disturbances, fatigue/malaise/weakness/lethargy, diarrhea, rash

What are the drug interactions of garlic?

Anti-coagulants and anti-platelet drugs — additive effects Allicin may induce the 3A4 system while garlic oil may inhibit the 2E1 system.

What are the drug interactions of cannabinoids regarding both THC and CBD?

Any CNS depressant will cause additive depression. THC is metabolized by the 2C9 and 3A4 pathways and CBD is metabolized by 2C19 and 3A4 pathways. Additionally, THC induces 1A2 and CBD inhibits 3A4. All may contribute to DIs.

What is the summary for wheat?

As a source of nutrition, wheat is an important crop and foodstuff.

What is the recommendation for barley grass?

As part of a sensible diet or as an additional supplement, barley is probably safe and effective as a balanced approach to nutrition and self care.

What is saw palmetto used to treat?

BPH

What are the reported uses of barley grass?

Barley is most often used as adjunctive alternative therapies for heart health and hyperlipidemia.

What is the summary for barley grass?

Barley-based foods are one of the recognized "heart healthy" foods that may contribute to overall benefits in cardiovascular performance.

What are the drug interactions of elderberries?

Based upon the potential immunomodulating effects of elderberry constituents, co-administration with immunosuppressants is discouraged (the immunosuppressant effects may be negated).

What receptors does CBD act on?

CBD appears to have partial agonist/antagonist or pure antagonist activity at CB receptors and perhaps other (GPCR 55) receptors

What are the demonstrated actions of cannabinoids regarding CBD?

CBD has demonstrated at least some activity in reducing certain types of seizures (Lennox-Gestaut, Dravet) in children.

Where are CB1 receptors located?

CNS

What are the reported uses for turmeric?

Cancer (breast, colon, esophageal, oral, skin, stomach) prevention Atherosclerosis Cholelithiasis GI upset Inflammatory disease Hepatic disorders IBS Parasitic infections

What are the toxicities of cannabinoids regarding THC?

Cardiovascular (arrhythmia, tachycardia), paranoia, psychosis

What is the clinical data for cannabinoids?

Clinical data is supportive enough for the approval of synthetic THC drugs (dronabinol, nabilone) for use in appetite stimulation in cancer/HIV patients and anti-nausea in cancer patients. A mixture of cannabinoids (nabiximols) is approved elsewhere and being fast-tracked by the FDA for control of muscle spasms in MS patients. CBD (epidiolex) has been approved for the treatment of Lennox-Gestaut and Dravet syndrome associated seizures in children. Effects on intraocular pressure are too short in duration and existing medications are better, indicating cannabis is not an effective alternative for glaucoma patients.

What is echinacea used to treat?

Common cold

What is the recommendation for ashwagandha?

Considered possibly safe when taken short term at lower doses, except for pregnant patients. It is considered possibly effective in reducing stress and stress-related weight gain, but insufficient data exist for any other uses. Data on usefulness and demonstrated efficacy is generally lacking and should be considered when making recommendations.

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What are the side effects, toxicities, and warnings of garlic?

Contact Dermatitis Diaphoresis Dizziness Garlic odor Hypothyroidism Irritation of mouth, esophagus, stomach Nausea and vomiting

What are the active sources of wheat grass?

Couch grass/dog grass/Scotch quelch

What are the reported uses of wheat?

Currently, it is promoted as an alternative treatment for ulcerative colitis.

What does the clinical data of cranberries indicate?

Daily ingestion of cranberry can decrease the incidence of recurrent UTI

What are the drug interactions of ashwagandha?

Data are lacking on potential drug interactions. It is reported to interfere with assays for digoxin.

What are the demonstrated actions of cranberries?

Decreases the adherence of pathogenic organisms (notably E. coli) to epithelial surfaces of the bladder.

DSHEA

Dietary Supplement Health and Education Act of 1994

What are the three questions that should be asked when considering an herbal therapy as a recommendation and how would they be answered?

Does the therapy work? - Look at the literature to see if there is any efficacy that has been established by scientific data (in vitro, in vivo, clinical) Is it safe? - Use the literature (PubMed, Natural Medicines, Facts & Comparisons) to see the possible safety profile when it comes to ADRs, toxicity, and drug interactions Is it a good product? - Look for one of the three quality assurance seals (NSF, USP, CL)

What is the recommendation with elderberries?

Early evidence seems to support the use of elderberry for specific viral infections. It appears to be at least modestly effective and relatively safe.

What are the side effects of cannabinoids regarding THC?

Euphoria/high, tachycardia, palpitations/arrhythmia, hypotension, anxiety, nervousness, depersonalization, confusion, hallucination, short-term memory loss, drowsiness, vertigo, dry mouth, and if smoked, typical ADRs associated with smoking (SOB and if chronic, increased risk of COPD, emphysema, lung cancer)

What are the demonstrated actions of elderberries?

Extracts of elderberry have been shown to have some anti-viral activity (possibly by either inhibiting viral replication and/or preventing viral entry into host cells) and immunomodulating activity (evidences supports both increased and decreased synthesis and release of various cytokines and immune/inflammatory mediating signalling agents)

What are the constituents of cranberries?

Fructose and an unidentified high molecular weight compound

What are the side effects, toxicities, and warnings for turmeric?

GI ulceration Contact Dermatitis May cause additive bleeding with NSAIDs, anti-coagulants, anti-platelet drugs May interfere with (decrease effect of) immunosuppressive drugs

What are the clinical remarks of garlic?

Garlic has been tested in human subjects with the following results: Lower total cholesterol, no better than the HMG-CoA reductase inhibitors (mortality and morbidity tests have not been performed) - Lowered diastolic, but not systolic, blood pressure - Reduce morbidity in AIDS patients (very preliminary and few patients) - Unclear benefits after 6 months

What are the constituents of aloe?

Gel: The gel is composed primarily of water with small amounts of enzymes, vitamins, minerals, the polysaccharides acemannan and glucomannan, and other components Latex: The latex contains the anthraquinone glycosides Aloin A and Aloin B (barbaloin and isobarbaloin)

What are the reported uses of garlic?

Hyperlipidemia and hypertension — also promoted for AIDS and the prevention and treatment of cancers

Quality Assurance - USP Verified

Independent, non-profit, third party Manufacturers and Suppliers VOLUNTARILY participate Assurances - all ingredients listed are present in their declared amounts, there are no harmful contaminants, product will release said ingredients, product is manufactured under good manufacturing practices (GMPs)

What is elderberry used to treat?

Influenza

What are the demonstrated actions of turmeric?

Inhibition of carcinogenesis (metabolism of carcinogens and antioxidant activity) Possibly effective in cholelithiasis (reduced intestinal cholesterol uptake in rats) Anti-inflammatory (LOX and TXA2 inhibition; stimulate release/increase sensitivity/reduce metabolism of cortisol) Anti-infective (possible anti-parasitic/viral activity; increase CD4 counts; decreased viral transport into health cells)

What are the demonstrated actions of saw palmetto?

Laboratory data indicates the following pharmacologic effects: Inhibition of 5-alpha reductase (in vitro) Antagonism of DHT at androgen receptors Some evidence exists for Anti-inflammatory actions (MOA unknown) Inhibition of prolactin (MOA unknown) Inhibition of prostatic cell proliferation

What is the clinical data of ashwagandha?

Limited clinical studies have supported some of the anxiolytic/CNS effects, immunomodulating (stimulatory), and anti-inflammatory activities, but better, larger trials are needed

What are the problems with DSHEA (3)?

Manufacturer's are NOT required to submit evidence of safety to the FDA No FDA regulations specifying how safety is to be established. FDA bears the legal burden of proving that a product is unsafe before it can be removed from the market.

What are the drug interactions of cranberries?

May acidify the urine, altering excretion of other drugs Inhibits the cytochrome P450 2C9 pathway

What are the side effects and toxicities of orally administrated aloe?

May cause gastric upset Chronically, may cause irreversible damage to GI mucosa and renal failure Electrolyte imbalance (especially hypokalemia) Spontaneous abortion Tolerance develops to the laxative effect

What are the side effects and toxicities of cranberries?

May cause gastric upset or diarrhea

What are the drug interactions of orally administered aloe?

May increase the actions/toxicity of digoxin, anti-arrhythmics, glucocorticoids, and thiazide and loop diuretics.

What is the clinical data of saw palmetto?

Men, 60-70 years old with the criteria of urinary frequency and urine flow rate - Significant improvement relative to placebo (Champault et al. 1984) Similar in efficacy relative to finasteride (Carraro et al. 1996) - Less (though not significantly) effective than alpha-1 adrenergic blockade

What are the ADRs of elderberries?

Minimal side effects like GI upset

What are the reported uses of cannabinoids regarding both THC and CBD?

Most patients use THC for its appetite stimulation, anti-nausea, or analgesic activity, although other uses are reported. CBD is used primarily for its anti-convulsant effects, although other uses are reported.

What are the side effects, toxicities, and warnings of wheat?

Nausea, anorexia, and constipation

What are the clinical test interactions of wheat?

None known

What are the suggested drug interactions of wheat?

None known

Quality Assurance - NSF Certification Program

Not-for-profit, non-governmental - National Sanitation Foundation Certifies that the contents match label information Assurance - contains nothing that is not indicated on the label & nounacceptable levels of contaminants.

What are the suggested drug interactions of barley grass?

Oral anti-diabetic agents or insulin may result in exaggerated hypoglycemia. Barley may also slow the absorption rate of orally administered drugs.

What are the reported uses of aloe?

Orally as a laxative and topically to promote healing, especially with burns, sunburn, and minor abrasions

What are the constituents of cannabinoids?

Over 60 different terpenoidal compounds classed as cannabinoids, with the most active being cannabidiol (CBD) and Δ-9-tetrahydrocannabinol (THC)

Additionally, the survey indicated that the top three reasons for younger people (<55 years) taking dietary supplements were:

Overall health and wellness Increase energy Improve immune health

Additionally, the survey indicated that the top three reasons for older people (>55 years) taking dietary supplements were:

Overall health and wellness To fill nutrients gaps in diet For heart health or bone health

What are the reported uses of ashwagandha?

Patients report using ashwagandha for numerous conditions, reflecting perhaps its similarity to ginseng as an adaptogen.

Where are CB2 receptors located?

Periphery

What are the contraindications of saw palmetto?

Pregnancy and women of child-bearing age due to actions potentially similar to those produced by finasteride

What are the reported uses of echinacea?

Prevention or treatment of common cold

Echinacea is also known as what?

Purple coneflower

What is the active part of turmeric?

Rhizomes

What is the recommendation for wheat?

Safe as a foodstuff and probably safe as an alternative therapy, although long-term data are lacking.

What are the reported uses of saw palmetto?

Saw Palmetto is claimed to be effective in the treatment of genitourinary problems, including benign prostatic hypertrophy (BPH). Other purported uses are to treat male pattern baldness, increase sperm production, to increase breast size in women, to increase libido, to produce mild diuresis.

What is the recommendation for garlic?

Scientific and clinical evidence supports some therapeutic benefits from garlic in lowering lipids and blood pressure and reasonable doses. Other reported effects only occur at potentially dangerous doses or have no basis for efficacy.

What are the active sources of barley grass?

Scotch barley/pearl barley

What is the recommendation for cranberries?

Sensible use of cranberry juice is probably safe and possibly effective in reducing incidence of recurrent UTI

Regarding the efficacy of aloe vera, some papers indicate that aloe is better than (3):

Silver sulphadiazine, tea tree oil, and saliva

What are the demonstrated actions of barley grass?

Soluble fibers such as those found in barley have been demonstrated to reduce the risk for certain (colon) cancers, reduce circulating levels of LDL and total cholesterol, and lower blood pressure. Soluble fibers may increase bile acid secretion and/or modulate lipid handling to lower cholesterol. Hordenine possesses mild adrenergic stimulant effects.

What is the recommendation for saw palmetto?

Some active constituent of saw palmetto does appear to have beneficial effects in the treatment of BPH, although the exact mechanism is unknown. Saw Palmetto does not apparently alter prostate size. Use should be controlled and supervised by healthcare professionals to minimize potential risks and to judge efficacy of treatment.

What are the demonstrated actions of cannabinoids regarding THC (6)?

Stimulating appetite Suppressing pain Inhibiting nausea associated with cancer chemotherapy Reducing muscle spasm associated with MS Lower intraocular pressure Immunosuppression

What is aloe used to treat?

Sunburns

What is the recommendation with turmeric?

The anti-oxidant activity of curcumin is approximately that of vitamins C and E. Preliminary research supports beneficial pharmacologic actions of tumeric, but additional research and clinicals are needed.

What is the active source of cranberries?

The berries

What is the active source of saw palmetto?

The berries

What is the active part of elderberries?

The berries (and sometimes flowers)

What is the active source of garlic?

The bulbs (edible portion)

What is the active source of echinacea?

The dried roots and rhizomes, the juice of fresh roots, and the aerial portions of Echinacaea angustifolia, E. pallida, and E. purpurea.

The active constituents of ashwagandha are structurally similar to what?

The ginsenosides of ginseng and are often called "Indian ginseng."

What are the clinical test interactions of barley grass?

The hordenine constituent has been reported to cause a false positive for opiates in drug tests.

What are the toxicities of elderberries?

The leaves, stems, and unripe berries contain a much greater concentration of the cyanogenic glycosides that may yield HCN upon metabolism. There are cases of cyanide poisoning in some patients. Presentation begins with severe GI upset (nausea, emesis, diarrhea) followed by weakness, dizziness, numbness, and stupor.

What are the demonstrated actions of garlic?

The mechanisms of action are not Known, although it has been suggested that it may inhibit HMG Co-A reductase. For pharmacodynamic effects, garlic has been shown to decrease total cholesterol, triglycerides, LDL and to increase HDL (animals and humans), decrease blood pressure (animal and human -- significant reductions in diastolic pressure, no significant changes in systolic pressure), possess anti-infective activity (in vivo and in vitro), inhibit platelet aggregation (methylallyltrisulphide and ajoene), anti-carcinogenic activity (mice), decrease GI motility (rodents)

What are the side effects of ashwagandha?

The most common side effects are limited to GI upset. Rash and sexual ADRs (decreased libido) have also been reported. More seriously, some patients have responded with hepatotoxicity. It has also been reported to be abortifacient.

What is the active source of ashwagandha?

The roots and berries

What are the demonstrated actions of echinacea?

The simple phenylpropanoid chicoric acid stimulates phagocytosis and the high molecular weight polysaccharide acts via arabinogalactan to increase tumor necrosis factor α activity, both of which will produce an immunostimulant effect, including increased synthesis of interferon. Increase leukocyte chemotaxis Anti-inflammatory and local anesthetic actions and some anti-infective actions. Long-term therapy has demonstrated an immunosuppressant effect, while short term administration causes immunostimulation, thus classifying echinacaea as an immunomodulating agent. Studies examining echinacaea are conflicting, with many indicating some benefit in shortening the duration and severity of the common cold and others indicating no effect. Some newer studies were not as supportive of abeneficial effects, however, it has also been pointed out that these newer studies indicating no effect may have flaws in their design.

What is the active source of cannabinoids?

The stems, leaves, and flowering tops (in increasing order of concentration) of Cannabis sativa

What is the active source of aloe?

The thick succulent leaves

What is the recommendation for echinacea?

There is much debate over the usefulness of echinacaea and concern over standardization issues. The general concensus is that if there is any benefit, it is for the treatment of common cold and not for its prevention. Patients should be counselled to not take the herb chronically. It appears to be relatively safe and possibly effective in reducing the symptoms and duration of cold in some individuals.

What is the recommendation for aloe?

Topically, the use of aloe is relatively safe and possibly effective. Oral use may be effective for short term effects, but patients should be warned to limit dose and duration due to severe toxicities

Differences Between U.S. and European Countries Regarding Regulation of Herbal Products

U.S. - wide variability in products marketed with no required standardization Europe - products regulated as pharmaceuticals, requiring Good Manufacturing Practices (GMPs) and Good Agricultural Practices (GAPs), as established by law.

What are the reported uses of cranberries?

UTI

What are cranberries used to treat?

UTIs

What are the warnings with elderberry use?

Use of elderberry in patients with auto-immune diseases is not recommended

What are the constituents of turmeric?

Volatile oil curcumin, containing various curcuminoids — tumerone, altantone, diaryl heptanoids, and zingiberone

What are the constituents of wheat?

agropyrene and apigenin, high in chlorophyll and various vitamins and minerals

What are the constituents of barley grass?

beta-glucan (5-10%), a soluble fiber, the alkaloid hordenine, various sugars, fatty acids, and vitamins

Safety Issues in the US: Adverse effects may occur, resulting from direct actions of (4):

constituents, allergic reactions, contaminants, drug interactions

Under DSHEA, a manufacturer MAY make _________ claims, e.g. "contains 200 mg. calcium" or "high in calcium"

content

Safety Issues in the US: Many "alternative therapies" were found to contain undeclared drugs, such as __________ and __________.

diethylstilboestrol, indomethacin

The use of supplements was essentially _________ when comparing age, region, gender, income, and education

equal

Saw palmetto may produce a __________ prostate-specific (PSA) result, baseline measurements should be made _______ to initiation of therapy

false-negative, prior

People who are more _________ are more likely to use supplements

health conscious (try to have a balanced diet, do not smoke, visit physician regularly, try to get adequate rest/sleep, try to maintain healthy weight, exercise regularly)

Smoking is a(n) ___________ form of delivery for medical marijuana.

invalid

Safety Issues in the US: Many compounds found in Asian patent medicines have been found to contain high levels of _______, _______, and _______.

lead, mercury, arsenic

What are the constituents of saw palmetto?

n-Hexane liposterolic extract, containing lauric acid and other fatty acids, phytosterols, polysaccharides, monoacylglycerides

People mostly trust _________ for information on supplements while ________ was the top purchasing factor

physicians, cost

Under DSHEA, a manufacturer may NOT claim that their product can "____________, ____________, ____________, or ____________ a specific disease"

prevent, cure, mitigate, diagnose

Safety Issues in the US: Public perceives the products as _______ (if allowed on market, must be _______ mentality)

safe

Under DSHEA, a manufacturer MAY make specific claims as to structure and/or function without proof of _________ or __________.

safety, efficacy

Because herbal products are regulated as dietary supplements, their doses are reported as _________

serving sizes

CB receptors are ____________ receptors and are coupled to the second messenger system __________ which reduce adenylyl cyclase activity leading to inhibit the formation of cAMP and inhibit L-type calcium channels to reduce calcium influx

typical seven-transmembrane G protein coupled, Gi protein

Safety Issues in the US: Many times the health professional is __________ their patient is taking these products.

unaware

Garlic is a proven ________ deterrent

vampire