Chief’s Conference Herbal Supplements: A to Z

1. Chief’s ConferenceHerbal Supplements: A to Z Katina Robertson, MD Emory University Family Medicine Program Thursday, January 7, 2010

2. Aloe VeraAloe vera, Aloe barbadensis • Common Names —aloe vera, burn plant, lily of the desert, elephant's gall • History: used in Ancient Egypt– “plant of immortality”. Presented as burial gifts to deceased pharaohs • Leaves contain clear gel often used topically • Oral preparation (juice or dried substance “latex”) from inner lining of green leaves

3. Aloe Vera Uses Lichen Planus Skin burns Wound healing Ulcerative Colitis– 2004 randomized, placebo controlled trial. 44 patients, 100mL BID x 4wks. 30% vs 7% had clinical remission and 37% vs 7% had clinical improvement. • Constipation– strong laxative properties: aloin, aloe-emodin and barbaloin • Genital Herpes– hydrophyllic cream prep • Psoriasis Vulgaris • Seborrheic Dermatitis • Aphthousstomatitis “canker sores” • DM type II

4. Aloe Vera Adverse Events • Diarrhea, GI upset • Hypoglycemia in combination with oral diabetes meds • case report of aloe vera induced hepatitis in Des Moines, Iowa VAMC (Annals of Pharm, 2007) • In 2002, FDA required that all OTC aloe laxative products be removed from the U.S. market or reformulated because the companies that manufactured them did not provide the necessary safety data

5. Black Cohoshactaearacemosa or Cimifugaracemosa • Common Names: black snakeroot, bugbane, bugwort, rattleroot, rattletop, rattleweed, and macrotys-- Insects avoid it • History: Native American medicine – malaise, Gyn d/o, kidney d/o, malaria, rheumatism and sore throat. 19th century home remedy, diuretic, and to cause menstruation • Member of buttercup family, perennial plant in N. America • Oral preparation are from the roots and rhizomes (underground stem)– Remifemin most well studied prep

6. Black Cohosh • Use: primarily hot flashes, post-menopausal sxs • ? Estrogenic properties • Evidence: None consistent • Kupperman Index-- measures of hot flashes, depression and insomnia (not vaginal dryness) • German study: 60 women s/p hysterectomy. Compare 8 mg/d of a black cohosh extract version of Remifemin with three estrogen regimens: estriol (1 mg/day), conjugated estrogens (1.25 mg/day), and estrogen-progestin (2 mg estradiol / 1 mg norethisterone acetate) for 6mo. In all groups modified Kupperman index was significantly lower at 4, 8, 12, and 24 wks post Tx. Black cohosh decreased symptoms similarly to the other treatments. • NCCAM (Natl Center on Complimentary and Alternative Medicine)–currently funding 12-month, RPCT on whether black cohosh is effective in reducing the frequency /intensity of menopausal sxs , improve QOL

7. Black Cohosh • Not regulated by FDA, compositions vary greatly • Common adverse effects: headaches, gastric complaints, heaviness in legs, weight gain • Case reports of acute hepatitis (one requiring liver transplant 3 wks after starting the herb) • U.S. Pharmacopeia (the standards-setting organization for foods and drugs) advises black cohosh products be labeled with : "Discontinue use and consult a healthcare practitioner if you have a liver disorder or develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice" • Relative contraindication if liver dz, breast cancer, pregnant • No published studies beyond 6 mos of use • If estrogenic-- long term effects on uterine tissue and CV risk?

8. Carnitine Kidneys efficiently conserve carnitine, so even carnitine-poor diets have little impact on the body's total carnitine content • Generic term for compounds that include L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine • Found in most cells in body… • Main Role: transport long-chain FAs into mitochondria for oxidization. • Concentrated in skeletal and cardiacmuscle that utilize FAs for energy • Healthy children and adults DO NOT need to consume carnitine from food/ supplements, as the liver and kidneys produce sufficient amounts from the AAs lysine and methionine to meet daily needs • Animal products like meat, fish, poultry, and milk are the best sources. • Adult diet– 60-180mg/d

9. Carnitine • FDA approved to treat carnitine deficiencies only • Primary-- genetic d/o manifests w/ cardiomyopathy, Skeletal muscle weakness, hypoglycemia • Secondary– renal dz or drugs (chemotx, antiseizure, pivampicillin) that reduce absorption/increase excretion • Other Uses • Athletic performance– no evidence it improves exercise/physical performance • Aging– decline in mitochondrial function thought to contribute to aging, carnitine decreases with age. Meta-analysis of PCT- DB suggests acetyl-L-carnitine may reduce deterioration in older adults with mild cognitive impairment from Alzheimer's disease . Subjects took 1.5-3.0 grams/day of acetyl-L-carnitine for 3-12 months. • CV D and PVD • DM type II-- recent analysis of two multicenter clinical trials of subjects with either type 1 or type 2 diabetes found Tx with acetyl-L-carnitine (3 g/day orally) for one year provided significant relief of nerve pain and improved vibration perception in those with diabetic neuropathy. The treatment was most effective in subjects with type 2 diabetes of short duration. Diabetes Care 2005;28:96-101 • Male infertility • ESRD and HD patients (studies small, not PCT or blinded)

10. Carnitine • At doses of 3g/day or more… adverse events • Nausea/vomiting • Abdominal cramps • Diarrhea • “fishy” body odor • Muscle weakness in uremic pts • ? Lower seizure threshold

11. DandelionTaraxacumofficinale • Common Names— dandelion, lion's tooth, blowball • Dandelion greens are great source of Vitamin A • Historically– used in Native American and traditional Arabic medicine to treat liver, spleen, kidney disease • Leaves are dried to make teas, capsule, extracts • Today, used as diuretic and for minor digestive problems • No evidence for use to treat any condition • Side Effects: generally safe, rare reports of GI upset, diarrhea

12. EchinaceaEchinacea purpurea, Echinacea angustifolia • Common Names— echinacea, purple coneflower, coneflower, American coneflower • Believed to stimulate the immune system • Traditionally used to treat/prevent URI or viral syndromes. Less commonly for boils/acne • Plant and roots are dried to make teas, squeezed juice, extracts or preps for topical use • No evidence for use to treat any condition • Side Effects: if taken orally– allergic rxns(rash, anaphylaxis), asthma flare. Worse in those with atopy and allergies to daisy family (ragweed, chrysanthemums, marigolds, etc)

13. Flaxseed/Flaxseed OilLinumusitatissimum • Common Names— flaxseed, linseed • Uses: • Flaxseed itself contains lignans (phytoestrogens, or plant estrogens): laxative, hot flashes, breast pain • Flaxseed oil preparations lack lignans- arthritis • Both-- hyperlipidemia, cancer prevention. • Contains soluble fiber • Whole or crushed flaxseed can be mixed with H2O or juice. Also in powder and capsule form. • Some studies suggest: alpha-linolenic acid (found in both) may benefit people w/ CAD. No consistent data. • Rare side effects: b/c fiber source, take w/ water to prevent constipation or intestinal blockage

14. GinkgoGinkgo biloba • Common Names— ginkgo, Ginkgo biloba, fossil tree, maidenhair tree, Japanese silver apricot, baiguo, baiguo ye, kew tree, yinhsing • ginkgo tree- one of oldest types of trees in the world • Ginkgo seeds- used in traditional Chinese medicine for thousands of years. Cooked seeds occasionally eaten. • Leaf extracts  tablets/capsules, teas, skin products • Uses: • Traditionally- asthma, bronchitis, fatigue, tinnitus • Today- improve memory (Alzheimer’s, dementia), intermittent claudication, sexual dyfunction, multiple sclerosis, tinnitus

15. GinkgoGinkgo biloba • Evidence • Ginkgo biloba for Prevention of Dementia study (JAMA 2008) • RPCT-DB5 academic ctrsbetw 2000-2008, 3,069 elderly pts age ≥ 75 with normal cognition or mild cognitive impairment (MCI) • placebo vs 120mg G biloba extract BID • Q6 month eval x median 6.1 yrs . Primary outcome incident dementia or AD • Ineffective in slowing cognitive decline. 246 (placebo) vs 277 (receiving G biloba) • Ginkgo for Memory Enhancement- Six-week RPCT- DB. 203 pts age ≥ 60 without cognitive impairment. Results- No improvement in performance on standard neuropsych tests of learning, memory, attention, concentration, naming or verbal fluency (JAMA 2002) • NCCAM future studies- asthma, MS, intermittent claudication, cognitive decline, sexual dysfunction 2/2 antidepressants, and insulin resistance IS IT OK TO TAKE… CAN’T HURT …. CAN IT?

16. GinkgoGinkgo biloba • Side Effects • Headache, nausea, GI upset, diarrhea, dizziness, allergic reactions • some data suggest  increase bleeding risk. Use caution in people on anticoagulant drugs, w/ bleeding d/o, or who have scheduled surgical or dental procedures • Uncooked ginkgo seeds contain a chemical known as ginkgotoxin, which can cause seizures. Consuming large quantities of seeds over time can cause DEATH!! • Ginkgo leaf and ginkgo leaf extracts appear to contain little ginkgotoxin

17. Horse ChestnutAesculushippocastanum • Common Names— horse chestnut, buckeye, Spanish chestnut • native to Balkan Peninsula, but grows throughout N. Hemisphere • Used for centuries for many diseases, NOW used to treat chronic venous insufficiency and hemorrhoids • seed extract standardized to contain 16 to 20 % aescin (escin), the active ingredient, is the most commonly used form. Also topical forms. • Small studies have found extract comparable to using compression stockings for venous insufficiency • Risks • Homemade preparations of horse chestnut should NOT be used. Raw horse chestnut seeds, leaves, bark, and flowers contain esculin, which is poisonous • When properly processed, extract contains little or no esculin. Can cause itching, nausea, GI upset

18. Kava Piper methysticum • Common Names— kava, kava kava, awa, kava pepper • Native to islands of the S. Pacific --member of pepper family • Used as ceremonial beverage in S. Pacific for centuries. • In past for fatigue, asthma, UTI, topical anesthetic. NOW used to treat chronic anxiety, insomnia, and menopausal sxs. • root and rhizome (underground stem) -used to prepare beverages, extracts, capsules, tablets, and topical solutions • Little evidence that it is efficacious in any diseases: ?anxiety Tx AND…

19. Kava Piper methysticum • Risks >> Benefits • Kava has been reported to cause liver damage, including hepatitis and liver failure • associated with several cases of dystonia (abnormal muscle spasm) • interact with several drugs, including anti-Parkinson's meds • Long-term and/or heavy use of kava may result in scaly, yellowed skin • Avoid driving/operating heavy machinery – can cause drowsiness

20. Licorice RootGlycyrrhizaglabra, Glycyrrhizauralensis • Common Names— licorice root, licorice, liquorice, sweet root, gan zao (Chinese licorice) • Grown mostly in Greece, Turkey, and Asia. Long h/o use in both Eastern and Western Medicine– stomach ulcers, bronchitis, sore throat, viral infxns – including Hep C • contains a compound called glycyrrhizin (or glycyrrhizic acid) • Peeled licorice root - available in dried and powdered forms. Also root in capsule, tablet and liquid extracts form • Licorice can be found with glycyrrhizin removed called DGL ("deglycyrrhizinated licorice“)- thought to have fewer side effects • Some evidence glycyrrhizin may reduce complications from hepatitis C BUT…

21. Licorice RootGlycyrrhizaglabra, Glycyrrhizauralensis • Risks: • In large amounts licorice containing glycyrrhizin can cause HTN, salt and water retention, and hypokalemia • safety of using licorice as a supplement for more than 4 - 6 weeks has not been thoroughly studied • Taking licorice together with diuretics or other meds that reduce potassium levels can cause severe hypokalemia • May interact with corticosteroids • May increase risk of preterm labor

22. Milk ThistleSilybummarianum • Common Names— milk thistle, Mary thistle, holy thistle, silymarin • Native to Mediterranean- used for thousands of yrs to treat many ailments, especially liver problems • Believed to have protective effects on liver & to improve liver fx, NOW used to treat liver cirrhosis, chronic hepatitis, GB dz • Other claims: lower cholesterol, insulin resistance in pts with DM II w/ cirrhosis, cancer cell growth (breast, cervix, prostate) • Biological active part– silmarin from seeds to make capsules, extracts, strong tea infusions • Currently mixed data on effect on liver fx. Curent phase II trial by NCCAM and NIDDK on use for chronic Hep C and NASH (fatty liver) • Side Effects– few… laxative effect, GI upset, bloating. Allergic Rxns to those allergic to daisy family (ragweed, chrysanthemum, marigold)

23. NoniMorindacitrifolia • Common Names— noni, morinda, Indian mulberry, hog apple, canary wood • evergreen shrub native to tropics of Pacific Ocean, from SE Asia to Australia, especially in Polynesia. • Traditional use- polynesian dye, topical prep for joint & skin conditions • Today, people drink noni fruit juice as general health tonic and for chronic dz(cancer, CVD, DM) • Lab research suggest has antioxidant, immune-stimulating properties • NCCAM and NCI -- ? efficacy in breast cancer prevention and Tx • Side Effects: • High in K+, avoid if on K+ rich diet or CRD • Reports of liver damage • Makers of noni juice “warned” by FDA about making unsubstantiated health claims

24. Evening Primrose OilOenotherabiennis • Common Names— primrose oil, EPO • native to N. America and contains gamma-linolenic acid (GLA), an essential fatty acid • Traditional use- eczema in 1930s • Today, mastalgia, RA, PMS, menopausal sxs, DM and cancer • Extracted from seeds-- usually put into capsules for use. • No effect on menopausal or PMS sxs. Mixed data on RA, mastalgia (small studies, ?able study design) • Side Effects: mild -- GI upset, HA

25. Red Yeast RiceMonascuspurpureus • Common Names— Angkak, Beni-koji, Hong Qu, Red Koji, Red Leaven, Red Rice, Red yeast, Zhitai, ZueZhi Kang • Brand Name– Cholestin3 • fermented product of the yeast species found on rice • medicinal and non-medicinal purposes in China since 900 A.D • contains several compounds collectively known as monacolins- monacolin K= powerful HMG-CoAreductaseinhiabitor and is the same chemical as lovastatin

26. Red Yeast RiceMonascuspurpureus • Evidence: • Recent studies- eval as alternative to statin for intolerant pts • Small RPCT- 62 pts in community cards practice (Annals 06/09) • ½ placebo & ½ RYR 1800mg  BID x 24wk • All patients were concomitantly enrolled in a 12-week therapeutic lifestyle change program • Primary outcome: LDL • RYR --LDL 43 mg/dL @wk 12 & 35 mg/dL@ wk 24 (P 0.001) • Plac-- LDL 11 mg/dL @wk 12 & 15 mg/dL@ wk 24 (P 0.011) • No difference in CPK, pain severity of liver enz • Risks: same as those for statinsinclmyopathy, rhabdomyolysis, hepatotoxicity • Monitoring organizations - large variation in the active compounds in RYR supplements- some supplements contaminated with citrinin, a nephrotoxicmycotoxin

27. Saw PalmettoSerenoarepens, Sabalserrulata • Common Names— saw palmetto, American dwarf palm tree, cabbage palm • Palm tree native to SE U.S. First use by Seminole Tribe in Florida • Today, urinary symptoms assoc w/ BPH. Also chronic pelvic pain, bladder d/o, decreased libido, and hair loss • Fruit is ground, dried, or whole and prepped in form of liquid extract, tablet/capsule, tea infusion • Mixed data-- 2006 DB, RPCT study of 225 men w/ mod-sev BPH showed no improvement w/ 320mg SP daily vs placebo. Primary outcome- max urinary flow rate and score on AmerUro Assn Sx Index (AUASI) (NEJM 2006) • Side Effects: mild- GI upset, ? decreased libido and breast tenderness in men

28. TurmericCurcuma longa • Common Names— turmeric, turmeric root, Indian saffron • Shrub related to ginger, grown in Asia and Africa • Known for warm, bitter taste and golden color-- commonly used in fabric dyes & foods (curry, mustards, & cheeses) • Today, heart burn, stomach ulcers, and gallstones, anti-inflammatory effects, cancer Tx • finger-like underground stems (rhizomes) - dried and oral prep as powder,capsules, teas, or liquid extracts. Also topical paste • Prelim animal data suggests anti-inflammatory and anti-cancer properties • Side Effects: mild- high doses indigestion. May worsen gallbladder dz

29. ValerianValerianaofficinalis • Common Names— setwall, Baldrianwurzel, and phu • perennial plant native to Europe and Asia, distinctive odor that many find unpleasant • Preps made from roots, rhizomes into teas, tinctures, extracts for capsules, tablets • 2nd century uses- insomnia. 16th century- anxiety, HA, palpitations, tremor. WWII- relieve stress from air raids • Today, treatment of insomnia disorders • Systematic review of several trials-- inconclusive data on efficacy for insomnia. Limitations- sample size/power, differing dosing amounts and sources of valerian • Side Effects: HA, dizziness, pruritis, GI upset

30. YohimbePausinystaliayohimbe • Common Names— yohimbe, yohimbe bark • Yohimbe tree -- tall evergreen native to W. Africa • Bark traditionally used as an aphrodisiac • Today, yohimbe bark as a dietary supplement-- in many forms, not regulated. • dried bark – used as tea or bark extract put into capsules/tablets and is a dietary supplement (not FDA regulated) • a regulated Rx form-- yohimbineHCl indic for Erectile dysfxTxbut cannot use this as evidence that the dietary supplement is efficacious. • No clinical trials conducted thus far on dietary supp version • Side Effects: assoc with HTN, tachycardia, HA, anxiety, dizziness, sleeplessness. Caution if MAOI, BP meds, TCAs, phenothiazines, renal disease

31. References Becker DJ, Godon RY, Halbert SC, French B, Morris PB, Rader DJ. Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial. Ann Intern Med. 2009;150:830-839, W147-149. Tisha R. Joy and Robert A. Hegele. Narrative Review: Statin-Related Myopathy. Ann Intern Med. June 16, 2009 150:858-868. http://dietary-supplements.info.nih.gov/Health_Information/Information_About_Individual_Dietary_Supplements.aspx Langmead L, Feakins RM, Goldthorpe S, Holt H, Tsironi E, De Silva A, Jewell DP, Rampton DS. Randomized, double-blind, placebo-controlled trial of oral aloe vera gel for active ulcerative colitis. Aliment PharmacolTher. 2004 Apr 1;19(7):739-47. Solomon PR, Adams F, Silver A, et al. Ginkgo for memory enhancement: a randomized controlled trial. Journal of the American Medical Association. 2002;288(7):835–840. DeKosky ST, Williamson JD, Fitzpatrick AL, et al. Ginkgo biloba for prevention of dementia: a randomized controlled trial. Journal of the American Medical Association. 2008;300(19):2253–2262. Bent S, Kane C, Shinohara K, et al. Saw palmetto for benign prostatic hypertrophy. New England Journal of Medicine. 2006;354(6):557–566.

32. Questions