Lecture 18 10.3.24 Herbal Slides Panahi Student Slides PDF

PHAR 721 Nutrition, Vitamins, Complementary and Alternative Medicine Dietary/Herbal Supplements: Central Nervous System Continued Ladan Panahi, PharmD, BCPS [email protected] 1  CYPinducee...

PHAR 721 Nutrition, Vitamins, Complementary and Alternative Medicine Dietary/Herbal Supplements: Central Nervous System Continued Ladan Panahi, PharmD, BCPS [email protected] 1  CYPinducee St. John’s Wort Who may consider this product? Patients with mild-moderate depression (ONLY AFTER CONSULTING THEIR DOCTOR) Steffre depression How should we counsel our patients? Do not use in pregnancy/lactation Therapeutic effects will not be evident for several weeks (4-6 weeks) Don’t abruptly discontinue can lead to SE Depression should NEVER be self-diagnosed or self- treated espthyroid interchangeable be gn Content of hypericin and hyperforin varies in commercial preparations; products may notptschghffy.fi Avoid in patients with bipolar disorder and schizophrenia worsen Drug interactions may Do not add to Rx antidepressants; can increase risk for serotonin syndrome SSRI 9SNRI ACDE babies in tom effect of drug in 2 pregnancy  Ginkgo biloba Extract (GBE) What is it? Leaves Ginkgo biloba is the 44th world’s oldest living tree ingredient species What is it used for? Alzheimer’s/dementia Tassen disease mentia sings 3  Ginkgo biloba Extract (GBE) How does it work? Contains flavonoids that may have antioxidant and free radical scavenging properties Improves blood circulationarterial vasodilationhappens erbalthat Contains ginkgolides, which are thought to have neuroprotective and antiplatelet bleeding properties risks Usual dose: 120-240 mg daily leaf extract in 2-3 divided doses 4  What is the evidence for efficacy? There’s no conclusive evidence that ginkgo is helpful for any health condition. Although some studies suggest that ginkgo may help to slightly improve some symptoms of dementia, the findings have been described as unreliable. Also, other studies have had conflicting findings. Ginkgo neither helps prevent dementia or cognitive decline nor prevents Alzheimer’s-related dementia from Ginkgo biloba getting worse—this is according to studies that include the long-term Ginkgo Evaluation of Memory Study, Extract (GBE) which enrolled more than 3,000 older adults and was funded in part by the National Center for Complementary and Integrative Health (NCCIH). 5 down the decline 2024 Update: Systematic review and meta-analysis found that Ginkgo biloba preparations combined with donepezil are more effective in improving Mini-Mental State Examination (MMSE) scores and activities of daily does not fix the issue living (ADL) compared to donepezil alone in the treatment of Alzheimer's disease. https://www.frontiersin.org/articles/10.3389/fnagi.2023.1124710/full 5 evidence present Ginkgo biloba Extract (GBE) risk for hemorrhage esp if taken w anticoag or antiplatelet What is the evidence for safety? Adverse reactions in large RCTs did not differ from placebo Reported side effects: GI upset, headache, dizziness, allergic skin reactions Seizures have been reported Hemorrhage has been reported in patients taking unstandardized ginkgo and anticoagulants/antiplatelets; possible additive effect (contradictory) Stop 7-14, ideally 14 days prior to surgery Thyroid and liver cancer observed in rodents after 2 years of use 6  Who may consider this product? Patients with dementia or Ginkgo cognitive impairment in addition to conventional treatment with consultation of physician biloba How should we counsel our patients? Do not use if pregnant/lactating Extract Patients taking antithrombotic agents or (GBE) antiplatelet should use ginkgo with caution and its use should be stopped at least 2 weeks before any surgical procedure 7  What is it? Hormone produced by the pineal gland, synthesized from tryptophan Secretion is inhibited by light and stimulated by darkness Melatonin Bovine, wine or synthetically produced What is it used for? Insomnia using wine to fall asleep Prevention of jet lag Sleep issues related to shift work nurses pharmacists 8 doing nightshift  Melatonin How does it work? Regulates sleep and circadian rhythms Supplementation increases concentrations to stimulate sleep regulation mechanisms When taken at bedtime, does not generally cause drowsiness, but makes attempts to sleep more successful 9 Melatonin Dosing and Clinical Efficacy Efficacy Shift work: studies on whether melatonin supplements help shift workers were generally small or inconclusive. Jet lag: Research suggests that melatonin supplements may help with jet lag. Chronic insomnia: According to practice guidelines from the American Academy of Sleep Medicine and the American College of Physicians, there’s not enough strong evidence on the effectiveness or safety of melatonin supplementation for chronic insomnia to recommend its use. https://jcsm.aasm.org/doi/epdf/10.5664/jcsm.6470 https://jcsm.aasm.org/doi/10.5664/jcsm.6470 Dosing Insomnia: 0.3–5 mg is taken orally 30–60 minutes prior to bedtime Jet lag: 2–5 mg taken the evening (between 5:00 and 10:00 pm) of arrival at the destination and at bedtime for the following 2–5 days 10  Melatonin What is the evidence for safety? Short Term: safe new data Long term: safety unknown. When used chronically for coming out sleep, endogenous melatonin can be decreased, uset of resulting in dependency for sleep Common ADR: drowsiness melatonin Less common ADRS: sedation, palpitations, N/V, for cancel headache, tachycardia, irritability, worsening of depressive symptoms, morning grogginess Drug and Disease interactions: neoplastic disease, CNS depressants, alcohol Yanca. 11  blue light affects melatonin don't use 2 hours before bed don'tgo straight to giving melatoninfor kids as it can mess w hormones try other methods first A study published in JAMA in 2023 found that products formulated as gummies with “melatonin” on the label were identified in the National Institutes of Health's Dietary Supplement Label Database. The study found that the actual amount of melatonin in these products varied widely, with some containing more than 10 times the labeled amount Cohen PA, Avula B, Wang Y, Katragunta K, Khan I. Quantity of Melatonin and CBD in Melatonin Gummies Sold in the US. JAMA. 2023;329(16):1401–1402. doi:10.1001/jama.2023.2296 The American Academy of Sleep Medicine issued a health advisory in 2022 warning parents to be careful about giving melatonin supplements to children. https://aasm.org/advocacy/position-statements/melatonin-use-in-children-and- adolescents-health-advisory/ 12  hormone Melatonin that affects reproductive system Who may or may NOT consider this How should we counsel our patients? product? Caution in children and adolescents For insomnia: take 30 minutes prior Caution/ avoid use in elderly to bedtime patients with dementia canwalkentia For jet lag: take between 5:00 pm- Pregnant and/or lactating women 10:00 pm day of arrival and at should avoid use bedtime the following 2-5 days GLS mI Long-term use only recommended Avoid products extracted from under the direct supervision of MD bovine pineal glands contaminationrisk we don't know the long term Risk of bacterial contamination effects of usingmelatonin and infection 13  Test Your Knowledge Select all that apply: St. John's wort is known to interact with which of the following types of medications, potentially reducing their effectiveness? A. Calcium carbonate (Tums®) B. Drospirenone and ethinyl estradiol (Yaz®) C. Lopinavir/ritonavir (Kaletra®) D. Metformin (Glucophage®) 14  Test Your Knowledge Which of the following medications is most likely to have an interaction when taken with ginkgo biloba? A. Pantoprazole(Protonix®) B. Dabigatran (Pradaxa®) C. Loratadine (Claritin®) D. Levalbuterol (Xopenex®) 15 Dietary/Herbal Supplements: Cardiovascular Health 16 Red Yeast Rice cooked wefungus turns purple What is it? Traditional Chinese culinary and medicinal product Produced through a fermentation process involving cooked rice kernels with a Monascaceae fungus, typically Monascus purpureus, which turns the rice reddish-purple due to its pigmentation capability The fermentation process with this yeast produces substances known as monacolins byproduct thisfermentation of What is it used for? Lower lipid concentrations in HEALTHY adults 17  How does it work? Contains Monaco in K Red = same chemical structure as lovastatin Yeast Rice Monacolins lower cholesterol by inhibiting HMG– CoA reductase, the rate-limiting step for cholesterol synthesis in the liver Especially lowers low-density lipoprotein (LDL) cholesterol, a potential risk factor for heart disease lowers LDD 18  Red Yeast Rice Legal Status In 1998 FDA ruled that any product containing a substantial amount of monacolin K was considered an “unapproved new drug” = against the law to sell as a supplement Some products may contain substantial amounts, others may contain little to none (we don’t know!) Amount of red yeast rice is labeled, not monacolin K content 19  What is the evidence for efficacy? Clinical research shows that taking certain red yeast rice products 1-5 grams daily for up to 24 weeks can lower total cholesterol by up to 23% and low-density Red Yeast Rice lipoprotein (LDL) cholesterol by up to 34% when compared with placebo or control The United States Food and Drug Administration may contain very little (FDA) considers red yeast rice products that contain statins to be illegal, unapproved drugs amount of The amount of monacolin K (lovastatin) in products is not always clearly stated on the label active ingredient Some red yeast rice products available in the US contain little or no statin constituents, but many still contain significant concentrations of statins One analysis shows that some of these products can contain up to 5 mg of statins per tablet It is not known whether red yeast rice products that contain a lower concentration of statins can significantly reduce cholesterol levels in patients with hyperlipidemia 20  United States, certain red yeast rice products have been declared illegal, Product because they contained an “unauthorized drug” Dosing Labels on these products usually state only the amount of red yeast rice that they contain, not the amounts of monacolin K or other monacolins, making selection of a high-quality, effective product more difficult Consumers have no way of knowing how much monacolin K is in each product Study of 28 supplements found that monacolin K content ranged from 0.09–5.48 mg per 1200 mg of red yeast rice Typical dose of red yeast rice is 1.2.- 2.4 gram daily in 2 divided doses (600 mg po bid) similar structure toflurostatin Red Yeast Rice bilateral symptoms What is the evidence for safety? Myopathy (muscle symptoms such as pain and weakness) Rhabdomyolysis (a condition in which muscle fibers break down, releasing substances into the bloodstream that can harm the kidneys) Liver toxicity (monitor LFT AST and ALT) Each of these three side effects has been reported in people who were taking red yeast rice Two studies supported by the National Center for Complementary and Integrative Health (NCCIIH) have indicated that some people who had been unable to tolerate statin drugs because of side effects (muscle pain or weakness) were able to tolerate red yeast rice. It is uncertain whether the smaller amount of monacolin K in the red yeast rice products, as compared with the amounts of active ingredients in the drugs, accounted for the greater tolerability or whether other factors were responsible.  Red Yeast Rice What is the evidence for safety? Absolute contraindication in pregnancy If culturing process not carefully controlled, the toxin Citrinin can form which may be nephrotoxic and mutagenic Citrinin has been shown to cause kidney failure in experimental animals and genetic damage in human cells In a 2011 analysis of red yeast rice products sold as dietary supplements, 4 of 11 products were found to contain this contaminant. Red Yeast Rice What are the significant drug/nutrient interactions? Monacolin K is extensively metabolized by CYP 3A4, thus CYP3A4 inhibitors or inducers may cause changes in monacolin K plasma concentrations. For this reason, the concomitant use of CYP 3A4 inhibitors such as grapefruit juice and some drugs (amiodarone, cyclosporine, verapamil, azole antifungals, macrolides, nefazodone, HIV protease inhibitors) may increase the risk of side effects Statins Alcohol  increase risk of hepatotoxicity https://www.sciencedirect.com/science/article/pii/S0735109720379997 Red Yeast Rice Who may consider this product? Those seeking a more natural approach and/or history of severe statin intolerance for mild hyperlipidemia Do not take if pregnant, patients at risk or have cardiovascular disease, or patients with kidney disease How should we counsel our patients? Do not take with statin medications Do not drink more than 2 alcoholic drinks day concomitantly Monitoring liver function baseline, 1–2 months after starting red yeast rice, and annually thereafter  Coenzyme Q10 (CoQ10) Also referred to as ubiquinone What is it? Fat-soluble antioxidant and endogenously produced A rate limiting cofactor in mitochondrial adenosine triphosphate (ATP) formation How does it CoQ10 is involved in many energy production functions and regeneration work? of other antioxidants Stabilizes membranes and may have vasodilatory and inotropic effects 26  What is it used for? Statin-associated adverse effects General antioxidant in cardiovascular disease Many more… Dose Range: Coenzyme 50-1200 mg/day Typical dosages studied have been 100 to 200 mg/day Q10 What is the evidence for efficacy? Statin Intolerance: statins decrease coenzyme Q10 production, possibly leading to muscle pain Randomized control trials: results conflicting Genetic differences may contribute to the variable responses to CoQ10 treatment In general, research is too limited for any conclusions to be drawn in research or conflicting results have been observed with CoQ10 use  ACC/AHA guidelines currently do not recommend initiation of nutritional supplementation as treatment (including CoQ10) in patients with current or previous symptoms of heart failure with reduced ejection fraction (HFrEF) (level of evidence B, class III recommendation). Although the results suggested an improvement in the primary MACE end point at 2 years, the small event numbers, difficulties in patient recruitment, and an unexpectedly large treatment effect with wide confidence intervals limit the interpretability of the results. ACC/AHA At this time point, CoQ10 initiation canNOT be recommended to patients with heart failure Guidelines for Heart https://www.ahajournals.org/doi/full/10.1161/C Failure Use IRCHEARTFAILURE.115.002639 Coenzyme Q10 What are the significant drug What is the evidence for safety? interactions? No serious side effects Warfarin, structurally similar to reported vitamin K recommend to Possible side effects (100 mg) doses Take with food to aid absorption Statin intolerance app: https://www.acc.org/StatinIntoleranceApp 30 Garlic What is it? The herb Allium sativum, best known for flavoring What is it used for? Hyperlipidemia Hypertension  Garlic How does it work? Produces allicin, the main component of garlic’s odor, and may be responsible for pharmacologic effect Animal and in vitro studies: hypotensive, hypolipidemic, antiplatelet, antioxidant, and anti- infective properties Increases levels of the vasodilator hydrogen sulfide, enhances nitric oxide production, and may inhibit angiotensin-converting enzyme  Fresh bulb : 1/2-1 raw clove daily (2 – 4 grams fresh garlic) Garlic Dried powder: 0.4-1.2 gram/daily Typical (providing 3 to 5 mg allicin/day) Dosing Enteric-coated capsule: 600-900 mg/day to help with “garlic breath”  What is the evidence for efficacy? Hyperlipidemia Garlic Efficacy May reduce total cholesterol and LDL cholesterol levels in people with high levels of these blood lipids The effect is small, and it may take more than 8 weeks before noting any improvement No improvement in HDL levels or triglycerides Hypertension Garlic supplements may be helpful for high blood pressure, but the evidence is limited  Garlic What is the evidence for safety? May increase risk of bleeding Stop prior to surgery or procedures Common side effects: bad breath, body odor, heartburn/GI upset What are the significant drug interactions? Saquinavir Anticoagulants Antiplatelets 35 Garlic Who may consider this product? Patients with mild hypertension Patients with mild hypercholesterolemia How should we counsel our patients? Increased risk of. bleeding Enteric-coated preparation may help decrease breath odor Odorless products may contain less allicin and may be less effective Garlic should be stopped 10–14 days prior to surgical procedures to avoid excess bleeding 36  Group of polyunsaturated fatty acids 3 fatty acids omega 3 Alpha-linolenic acid (ALA) Eicosapentaenoic acid (EPA) Docosahexaenoic acid (DHA) The human body can convert small amounts of What is Fish oil? ALA into EPA and DHA, but the main way people increase levels is to consume foods and supplements that contain omega-3s ALA is found in walnuts and some plant oils, such as flaxseed, soybean, and canola. EPA and DHA are high in oysters and such as salmon, fatty fish sardines, mackerel, herring, lake trout, and albacore tuna. 37  Fish Oil What is it used for? How does it work? Decrease triglycerides Decrease proinflammatory Decrease blood pressure cytokines (thromboxane A2 and Reduce cognitive decline in leukotrienes); Increase older patients noninflammatory cytokines (prostaglandin E3) Cardiac health??? Thought to decrease intestinal cholesterol absorption and inhibit enzymes involved in synthesis 38  American Heart Association (AHA) Guidance AHA science advisory 2017: omega-3 fish oil supplements may slightly lower the risk of dying after heart failure or a recent heart attack, but they do not prevent heart disease https://www.ahajournals.org/doi/10.1161/CIR.000000000000 0482 AHA science advisory 2019: 4 grams per day of prescription fish oil supplements were a safe and effective way to lower triglycerides, the most common type of fat in the body, in people with elevated levels. The same advisory warned consumers not to take unregulated supplements. https://www.ahajournals.org/doi/full/10.1161/CIR.00000000 00000709  AHA Guidance Continued 2022: randomized control trial published in the Journal of the American Heart Association found consuming 3 grams each day of EPA and DHA, in food or supplement form, may be the ideal dose to help lower blood pressure. About 4 to 5 ounces of Atlantic salmon provides 3 grams of omega-3 fatty acids. Fish oil supplement doses can vary but typically provide about 0.3 gram per pill. https://www.ahajournals.org/doi/full/10.1161/JAHA.121.0 25071 June 2023: randomized control trial published in the Journal of the American Heart Association taking more than 2 grams per day of DHA and EPA combined in supplement form may lower triglycerides and non-HDL cholesterol, but not LDL cholesterol. Non-HDL level is someone's total cholesterol minus their HDL, the "good" cholesterol that helps the body get rid of some of the harmful LDL. Must still be on statin to reduce LDL https://www.ahajournals.org/doi/10.1161/JAHA.123.0295 12  Usual dose: 1-4 grams of EPA/DHA per day Most studies have used products with an EPA:DHA ratio of 1.2:1 or 1.5:1 Vegetarian/vegan patients, DHA and DHA/EPA products made from algae are available but less clinical evidence is available for plant-based supplements Fish Oil Products have differing amounts – must read label Example of higher quality product: “1 gram fish oil” Dosing product labeled to contain “480 mg EPA and 370 mg DHA” per capsule Example of low-quality product: “1 gram fish oil” product with “250 mg EPA and 180 mg DHA” per capsule The American Heart Association recommends eating two servings of fish, particularly fatty fish, per week to help reduce heart disease and stroke risk. Two servings equal 6 ounces cooked. Fish Oil Mercury Concerns Mercury collects in flesh Most ingested fish oil is extracted from the skin Test of mercury levels in fish oil supplements showed no or barely detectable concentrations of mercury Methylmercury is a neurotoxin and is of special concern for pregnant women, breastfeeding mothers, and children Avoid predator fish consumption and limit American-farmed salmon consumption Other toxicity concerns: pesticides and dioxin can accumulate in the oil Recommend USP standard high-quality products Fish Oil What is the evidence for safety? Side effects include belching, indigestion, diarrhea, fishy halitosis, Freezing capsules or enteric coated may reduce “fish burp" Unknown whether people with fish or shellfish allergies can safely consume supplements use algae products Doses of fish oil >3 grams/day may inhibit platelet aggregation. Monitor patients taking fish oils and drugs that affect bleeding (e.g., anticoagulants, antiplatelets) Fish oil is not the same as fish (cod) liver oil Estoil Avoid eating fish with high mercury content (barely detectable in supplements tested) 43  Fish Oil Who may Patients with elevated triglycerides or mild consider this hypertension (no cardiovascular disease history) product? Discard products with a strong fishy or rancid smell or taste. This may be an indication of spoilage or How should we poor product quality Take with meals, freezing, or enteric coated may counsel our reduce “fish burps” patients? Take prescription product to minimize toxins Not all fish oil supplements are the same; must read label 44  Test Your Knowledge What is the primary component of fish oil that is believed to have health benefits? A. Saturated fats B. Omega-6 fatty acids O C. Omega-3 fatty acids D. Monounsaturated fats 45  Test Your Knowledge Which compound found in red yeast rice is believed to help lower cholesterol levels? A. Resveratrol B. Curcumin C. Monacolin K D. Anthocyanin 46