Introduction to Dietary Supplements

Transcription

1 By: Frank Caligiuri PharmD Assistant Clinical Professor Drake University College of Pharmacy and Health Sciences Dr. Frank Caligiuri, Pharm.D., is a Clinical Assistant Professor at Drake University College Pharmacy of Pharmacy and Health Sciences in Des Moines, Iowa. He received Doctor of Pharmacy Degree from Drake University and completed his residency at Iowa Methodist Medical Center before entering academia. His current clinical practice is at Unity Point Iowa Methodist Hospital where he works with the Internal Medicine and Pulmonary Services. His interest areas include infectious disease, cardiology and alternative medicine. He previous taught at UMKC School of Pharmacy, where hosted field courses focusing on pharmacognosy and alternative health modalities in Ecuador, Peru and California and is developing similar opportunities at Drake University. Dr. Caligiuri reports no actual or potential conflicts of interest in relation to this continuing pharmacy education activity. This CPE activity educates pharmacy technicians on the top dietary supplements that are available for patients, including their indications for use and potential safety concerns. Laws and regulations about dietary supplements and their labeling are also described in this module. Upon completion of this activity, Pharmacy Technicians will be able to: 1. Define dietary supplements and their frequency of use amongst the U.S. population. 2. Discuss the laws and regulations related to dietary supplements. 3. List the requirements for dietary supplement label in the U.S. 4. Recognize the different certifications for dietary supplements and their significance. 5. Discuss the indications for the most commonly used dietary supplements. 6. Identify potential safety issues including side effects or contraindications for common dietary supplements. CPE Information: UAN #: H01-T CEUs/Hours: 1 contact hour (0.1 CEU) Target Audience: Pharmacy Technicians Activity Type: Knowledge-based Initial Release Date: 1/1/2015 Planned Expiration Date: 1/1/2018 The Collaborative Education Institute is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This activity has been developed specifically for pharmacy technicians and is one of 10 activities in the TEAM series. Introduction to Dietary Supplements Dietary Supplement Use in the U.S. A dietary supplement is defined as a product that is intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, a mineral, an herb or other botanical, an amino acid, a dietary substance for use by man to supplement the diet by increasing the total daily intake, or a concentrate, metabolite, constituent, extract, or combinations of these ingredients. 1 Use of dietary supplements by the American population is significant with 49% of surveyed adults reporting use in the last 30 days. 2 In 2011, Americans spent more than $30 billion on dietary supplements, primarily as out of pocket expenditures. 3 A 2013 study published in the Journal of American Medicine Association (JAMA) regarding American adult dietary supplement use showed that the major groups found to be using supplements most often were women (54.4%), non-hispanic whites (53.8%) and adults over the age of 60 (67.4%). 2 The patients examined in this study used dietary supplements for various reasons, yet only about 23% used them on the basis of physician or health care provider recommendations. 2 The top reasons commonly reported for dietary supplement use included: improving overall health (45%), maintaining health (32.8%) and to maintain or improve bone health (25.2%). 2 The study also found an association between supplement use and overall improvement in health measures as users tended to be non-smokers, frequently exercised and had a lower body mass index (BMI). Another study published in 2013 by JAMA, looked at what U.S. adults actually thought about dietary supplements and their efficacy. 5 Results showed that nearly four out of every ten U.S. adults reported taking dietary supplements at some point in the past two years. 5 While the previous study reported the main reason for use of dietary supplements was to improve the health of specific organs, this study found that U.S. adults were using dietary supplements for a multitude of reasons, some of which included: to feel better, to improve overall energy levels and to boost the immune system. 5 One concerning note found in this study was that many adults used dietary supplements to treat potentially serious conditions/ symptoms without informing their physicians. Most dietary supplement use is dictated by patient s perceptions of the benefits and not based on scientific evidence. As a result, a majority of the adults surveyed said they would not stop taking their dietary supplement even if studies showed their ineffectiveness. 5 With the relatively high prevalence of dietary supplement use, it is important for pharmacists and pharmacy technicians to understand more about these agents. This continuing education activity will provide you with more information regarding the laws and regulations around supplement use and will review some of the more common dietary supplements. Laws, Regulations and Certifications In 1994, the Dietary Supplement Health and Education Act (DSHEA) was approved by Congress to regulate dietary supplements. The DSHEA Act states 2015 TEAM SERIES 1

2 The Use of Over-The-Counter Drugs During Pregnancy that dietary supplements are different from prescription and nonprescription medications because they are not intended to diagnose, cure, or treat a medical disease. 1 This act formally defined a dietary supplement as a product (other than tobacco) that is: 1 - Intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, a mineral, an herb or other botanical, an amino acid, a dietary substance for use by man to supplement the diet by increasing the total daily intake, or a concentrate, metabolite, constituent, extract, or combinations of these ingredients. - Intended for ingestion in pill, capsule, tablet, or liquid form. - Not represented for use as a conventional food or as the sole item of a meal or diet. - Must be labeled as a dietary supplement. Dietary supplements are regulated differently than prescription and nonprescription medications. They have far less stringent regulations than those of pharmaceutical drugs and are not regulated by the Food and Drug Administration (FDA). The different regulations include: 1 - Only manufacturers are responsible for determining the safety of their products, not the FDA. - Proof of efficacy is not required prior to marketing. - Dietary supplements do not require the manufacturer to submit the safety data to the FDA prior to their marketing, which is a requirement for prescription medications. - The FDA must prove the dietary supplement is unsafe prior to removing from the market. - Unlike drug manufacturers, dietary supplement manufacturers do not have to register with the FDA. - No FDA regulations exist that establish a minimum standard for manufacturing dietary supplements. The FDA does have the authority to: 1 - Stop the sale of dietary supplements proven to be unsafe. - Recommend, through regulation, good manufacturing practices (GMP). These include regulations addressing potency and stability of products and the cleanliness of manufacturing facilities. Similarly to over-the-counter medications, dietary supplements do have label requirements. All dietary supplement labels must include the following: 6 - The statement of identity (name of the dietary supplement). - The net quantity of contents statement (amount of the dietary supplement). - The nutrition labeling. - The ingredient list. - The name and place of business of the manufacturer, packer or distributor. Labels are also not permitted to make claims that the product actually prevents, cures, mitigates, or diagnoses a disease. 1 However, labels are allowed to make what are termed structure/function claims, as long as they are truthful. 7 A structure/function claim describes how the dietary supplement works in the body. An example of an allowable claim is this dietary supplement helps improve mood. In contrast, this dietary supplement treats depression would not be allowed on a label as it states it treats a disease, in this case, depression. 7 Because the FDA does not regulate dietary supplements, there has been concern over accuracy of the label in terms of contents and the quantity of the ingredients. For example, if one picks up a multivitamin at the store, no regulation exists to determine whether or not the label contents actually match what is contained in the pill. A study conducted by Gilroy et al in 2003 found that 10% of 59 Echinacea products tested actually contained no Echinacea, which was contrary to what the label stated. 8 Therefore, several organizations have been created to help develop analytical reference standards and certify the composition of dietary supplements. Consumers can look for certification seals from specific organizations to be confident of product testing and the supplement contains the standard quantity. There are currently four main certification organizations. 4 - AOAC International: A scientific organization that has been created as the gold standard for analytical methods to test dietary supplements. - U.S. Pharmacopeia (USP): A USPcertification seal on a product gives consumers the confidence that the product has been certified to contain the listed ingredients in the indicated amounts. It also ensures consumers that the product was manufactured under appropriate conditions. - Consumerlabs.com: This is an independent organization that tests dietary supplements. The CL Seal of Approval indicates that a product has been tested and the identity, purity and consistency of the products ingredients have passed rigorous testing. Consumers can also subscribe to the website to look up manufacturers to see if they have passedtesting or not by organization. - NSF International: An independent, nonprofit organization that verifies a product contains the labeled ingredients and contaminants or unwanted ingredients are not present. All of the above are certification seals a consumer can look for when selecting a dietary supplement. Pharmacists and pharmacy technicians should recommend that patients choose a dietary supplement with a certification seal so to be confident of the purity and composition of the product TEAM SERIES 2

3 Case Study: A new manufacturer of fish oil wants to market their product to the public. The marketing team wants to inform the consumer of the potential benefits of fish oil. Which would be a potential claim that the manufacturer could put on their label to help sell their product? A. Fish oil will prevent heart attacks. B. Fish oil will treat high cholesterol. C. Fish oil will cure all of your cardiovascular problems. D. Fish oil can improve your cholesterol. Answer: D. The manufacturer cannot put a claim on the label that fish oil prevents, treats, or cures any disease. Therefore, answers A, B and C can not legally be advertised on the label. Dietary supplements are allowed to make a structure/ function claim, which describes how the supplement works in the body. Answer D is a legal structure/function claim that the advertising team could put on the label to market their new product. Most Common Dietary Supplements (Both herbal and non-herbal) The following are ten of the most common herbal and non-herbal dietary supplements. We will review the indication(s) for use, common dose, potential side effects, safety precautions and summary of research that has been conducted for each supplement. To avoid repetition, it is important to know that patients who have a hypersensitivity or allergic reaction to any of the products or ingredients should not use the product. Glucosamine 4,9,15,20 Indications: Used to help symptoms of osteoarthritis (joint pain) Dose: Glucosamine sulfate 500 mg three times daily How it works: Glucosamine inhibits interleukin 1-beta, which reduces inflammation and cartilage degradation. Side effects: Peripheral edema, constipation, diarrhea, indigestion, headache, insomnia Precautions/contraindications: Avoid in patients allergic to shellfish. Research: Multiple meta-analyses (a large study that combines data from other studies to try to come to a single conclusion) conducted have shown conflicting results, with both significant benefits for osteoarthritis and absolutely no benefit for osteoarthritis reported. 4 A recent review published in 2012 concluded that because of the low incidence of side effects, glucosamine sulfate supplements should be considered as a treatment option for osteoarthritis. 9 However, the most recent guidelines published by the Osteoarthritis Research Society International (OARSI) guidelines for non-surgical management of the knee concludes that glucosamine should not be used as treatment for osteoarthritis but only for potential benefit of symptoms. 30 Coenzyme Q-10 (Ubiquinone) 4,10,15 Indications: A natural antioxidant found in the body used to improve cardiovascular health. Dose: mg daily. Doses over 100 mg should be divided into multiple doses. How it works: CoenzymeQ10, also called CoQ10 or by the chemically reduced form ubiquinone, is found in every cell of the body. 4 It is the rate-limiting step in ATP (energy) formation. Coenzyme Q10 also stabilizes cell membranes and helps dilate vessels. 4 Statin medications have been theorized to lower coenzyme Q10 levels in the body resulting in muscle pain but studies have not been able to prove this therapy. However, many patients who take statins often take coenzyme Q10 supplements based on this theory. 21 Adverse events: Typically well tolerated, but some patients may experience nausea, upset stomach, headache and dizziness Precautions/contraindications: Patients on warfarin (Coumadin ) should discuss with their health care provider prior to starting therapy due to a possible interaction. Research: Some studies have shown cardiovascular benefits while others have not. A meta-analysis conducted in 2012 did show that there was a benefit in clinical outcomes in patients with heart failure who took coenzyme Q Melatonin 4,11,12,15 Indications: Used to help those with sleeping disorders and jet lag. Dose: - Sleeping disorder: 5-10 mg taken 30 minutes prior to time of sleep - Jet lag: mg taken at 10 pm local time of the destination for 3 nights Adverse events: Sedation, somnolence, fatigue How it works: Melatonin is a naturally occurring hormone in the body that is secreted by the pineal gland in the brain. Once melatonin attaches to its receptors, it is thought to signal a pathway that begins to induce sleep. Precautions/contraindications: Those with severe allergies, liver or kidney problems should speak with their health care provider prior to taking. Research: Most data suggest that melatonin does help with sleep. A study concluded that melatonin can decrease time to onset of sleep, increase total sleep time and improve overall sleep quality. 11 Another study looked at melatonin use in medically ill patients against placebo and found that patients had faster sleep onset, improved quality and depth of sleep and increased sleep duration without producing drowsiness TEAM SERIES 3

4 Fish Oil 4,13,15 Indications: Used to lower high triglyceride levels (fats) and improve cardiovascular health. Dose: 2 to 4 grams daily in divided doses How it works: Typically, heart disease occurs when a patient has high cholesterol and a plaque forms. The plaque blocks blood flow in the arteries. A plaque can also rupture and a clot can form over the rupture, which can be the cause of a heart attack or stroke. Fish oil alters the plaque s inflammation and can stabilize vulnerable plaques. 13 It can also decrease triglyceride levels in the body by two ways: decreasing the formation of triglycerides and accelerating triglyceride destruction in the liver. 13 Adverse events: Fatigue, diarrhea, nausea, abdominal pain Precautions/contraindications: Patients with fish allergy or patients with liver problems should speak to their health care provider prior to starting. It also may prolong bleeding, so those currently taking a blood thinning medication, such as warfarin, or about to have surgery should also consult their health care provider. Research: Fish oil was found to reduce triglyceride levels and be a safe addition for primary and secondary prevention of cardiovascular disease. 13 Garlic (Allium sativum) 4,15 Indications: Used to improve hyperlipidemia, hypertension, peripheral arterial disease and Type 2 diabetes Dose: mg daily How it works: When a garlic bulb is crushed, the inactive form allin is converted by the enzyme allinase to the primary active compound allicin. Allicin then acts through multiple potential pathways in the body to cause dilation of the veins, which can lead to a decrease in blood pressure. Adverse events: Nausea, vomiting and heartburn Precautions/contraindications: Garlic supplements need to be stopped 7-10 days prior to surgery as they can increase the risk of bleeding. Patients on blood thinning medications, such as warfarin, should not take garlic as it can increase the risk of bleeding. Research: Studies have shown that garlic can reduce total cholesterol and low-density lipoprotein (LDL) or bad cholesterol by a modest amount, which is typically seen in the first few months after use. Studies have shown mixed results for all other indications. Echinacea (Echinacea purpurea) 4,15 Indications: Used to help build a more effective immune system in order to prevent and treat colds and other respiratory infections. Dose: Each product usually has different preparations and patients should follow label instructions. The typical duration for treatment of an acute illness is days. How it works: Exact mechanism is unclear, but it is postulated that it targets nonspecific cellular immune system components. It also has antiinflammatory properties. Adverse events: Mild gastrointestinal discomfort, headache and tingling of tongue Precautions/contraindications: Those with allergies to the Asteraceae family, asthma, allergic rhinitis, rheumatoid arthritis, HIV, multiple sclerosis and tuberculosis should avoid Echinacea. Chronic use should be avoided as this may have negative effects on the immune system. Research: Studies have shown Echinacea to slightly decrease the severity and duration of cold-like symptoms if taken at the very beginning of symptoms while other studies have shown no benefit. 4 Saw palmetto (Serenoa repens) 4,14,15 Indications: Used for treatment of benign prostate hyperplasia (BPH) or enlarged prostate Dose: 160 mg twice daily or 320 mg once daily How it works: Believed to inhibit the 5-alphareductase which is the enzyme the converts testosterone to dihydrotestosterone. This enzyme is the same enzyme targeted by prescription medications like finasteride (Proscar ) target. It also may inhibit cytosolic androgen receptor binding and have anti-estrogenic and anti-inflammatory effects on the prostate. Adverse events: Abdominal pain, nausea, vomiting, diarrhea Precaution/contraindications: Patients must speak with their health care provider to rule out prostate cancer prior to starting. Those on blood thinning medications should not use. Research: Studies have shown mild-moderate improvement in urinary symptoms with sawpalmetto use. Also, a study found that similar improvements of BPH symptoms and fewer side effects in patients taking saw palmetto compared with those taking the prescription medication finasteride (Proscar ). 14 Asian and American Ginseng (Panax ginseng and Panax quinquefolius ) 4,15 Indications: Classified as an adaptogen which means that it helps the body better overcome stress (both psychological and environmental). Also used to help with anemia, diabetes, insomnia, impotence and fever. Dose: mg daily How it works: Not exactly understood but actions Pharmacy 2015 TEAM SERIES Series 4 4

5 are attributed to ginsenosides. Adverse events: Headache, insomnia, anorexia, rash and changes in blood pressure. Precaution/contraindications: Patients with high blood pressure or diabetes should use with caution. It is recommended that use should be limited to 3 months due to a risk of estrogenic effects on the body (although research has not been able to confirm these effects). Patients on blood thinning medications, psychotropic medications, or on other CNS stimulants should avoid taking ginseng. Research: Studies have supported ginseng can help lower blood sugar in patients with diabetes as well as improve memory. 4 Cranberry (Vaccinium oxycoccos) 4,15 Indication: Used for urinary tract infections Dose: mg twice daily. Cranberry juice can also be used and doses range between 10 and 32 ounces per day How it works: Exact mechanism is unknown but likely the cranberry blocks bacteria from attaching to the urinary tract. Adverse events: Increase in kidney stones and diarrhea. The high sugar content of some juices may be problematic for patients with diabetes. Precautions/contraindications: Patients on warfarin should avoid as it can increase bleeding risk. Patients with history of kidney stones should use with caution. Research: Most studies have shown cranberry to help prevent urinary tract infections but not actually treat an infection. 4 other studies have shown it to be slightly less effective than traditional prescription medications. 4 In summary, the U.S. population frequently uses dietary supplements to maintain health and help with common ailments. Dietary supplements are not regulated as strictly as prescription and over-the-counter medications, which is a concern for the general public. There are various independent groups who certify products based on their content, purity and safety. Pharmacists and pharmacy technicians should encourage consumers to utilize products with these certifications. The type of products commonly used range from vitamins and anti-oxidants to herbs from all over the world. Pharmacists and pharmacy technicians should be familiar with the commonly used dietary supplements and their indications, as well as their adverse events and precautions. St. John s Wort (Hypericum perforatum) 4,15 Indication: Used to help with depression, anxiety and insomnia Dose: mg in divided doses with meals How it works: Alters the concentrations of serotonin, dopamine and norepinephrine in the brain. Adverse events: Tingling of skin, headache, nausea, dry mouth, agitation and skin reactions. Potentially causes sexual dysfunction. Precautions/contraindications: Avoid in patients with bipolar disorder and schizophrenia. Photosensitivity has been reported, so sunscreen use is recommended. Withdrawal symptoms can occur if stopped abruptly, so patients may need to taper off the herb. Since St. John s Wort interacts with many medications, patients should check with their health care provider prior to initiating therapy. Research: Many studies have shown St. John s Wort to be as effective as standard prescription therapies, often with fewer side effects. However, 2015 TEAM SERIES 5

6 REFERENCES: 1. Abood R. Pharmacy Practice and the Law Fourth Edition. Sudbury, MA: Jones and Bartlett Publishers; Bailey R, et al. Why US Adults Use Dietary Supplements. JAMA Intern Med. 2013;173: Considering a post-dshea World. Nutrition Business Journal. 2012;17: SUMM supp%20report%20FINAL%20standard. pdf Accessed October 8, Berardi RR, et al. Handbook of Nonprescription Drugs Fifteenth Ed. Washington, DC: American Pharmacists Association, Blendon R.J, et al. Users Views of Dietary Supplements, JAMA Intern Med, 2013;173: Dietary Supplement Labeling Guide: Chapter 1. General Dietary Supplement Labeling. U.S. Food and Drug Administration Available at GuidanceDocumentsRegulatoryInformation/ DietarySupplements/ucm htm Accessed September 29, Institute of Medicine (US) Committee on the Use of Complementary and Alternative Medicine. Washington, DC. National Academies Press, Gilroy CM, Steiner JF, Byers T, Shapiro H, Georgian W. Echinacea and truth in labeling. Arch Intern Med. 2003;163: Henrotin Y, Mobasheri, A and Marty M. Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis? Arthritis Res Ther. 2012;14: Fontino AD, Thompson-Paul AM and Bazzano LA. Effect on coenzyme Q10 supplementation on heart failure: a meta-analysis. Am J Clin Nutr, 2013;97: Ferraciolo-Oda E, Qawasmi A and Block MH. Metaanalysis: melatonin for the treatment of primary sleep disoders. PloS One. 2013;8(5):e Andrade C, Srihari BS, Reddy KP, et al. Melatonin in medically ill patients with insomnia: a double-blind, placebo-controlled study. Am J Resp Crit Care Med. 2004;170: Weitz D, et al. Fish oil for the treatment of cardiovascular disease. Cardiol Rev, 2010;18: Wilt T. Ishani A, Mac Donald D. Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2002;2:CD Lexicomp Database. Wolters Kluwer Health, Inc. Hudson, OH. Available at: Accessed October 1, U.S. Pharmacopeia. usp.org. Accessed October 1, NSF International. Accessed October 1, Consumer Labs. Accessed October 1, AOAC International. Accessed October 1, McAlindon TE et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis and Cartiallage. 2014;22: Pasternak RC et al. ACC/AHA/NHLBI Clinical advisory on the use and safety of statins. J of the American College of Cardiology. 2002;40(3): TEAM SERIES 6

7 POST ASSESSMENT QUESTIONS: 1. How are dietary supplements regulated differently than prescription medications? A. The FDA is not responsible for determining safety of dietary supplements; only the manufacturer is responsible. B. Proof of efficacy is required prior to marketing for dietary supplements, not prescription medications. C. The FDA can remove a dietary supplement from the market before proving it is unsafe. D. All of the above. A dietary supplement label must contain all of the following EXCEPT: A. Name of the dietary supplement B. Amount of the dietary supplement C. Who should avoid using the dietary supplement D. The list of ingredients found in the dietary supplement 2. You begin to investigate the dietary supplements available at your local pharmacy. You start to look at the labels on calcium/vitamin-d supplements. The labels seem to state a structure/function claim. Which claim would be considered legal to be found on a calcium/vitamin-d label? A. Prevents osteoporosis B. Promotes healthy bone growth C. Treats broken bones D. Cures osteoporosis 3. Which of the following is an organization that certifies the quality and purity of dietary supplement products available on the market? A. AOAC International B. U.S Pharmacopeia C. Consumerlabs.com D. NSF International E. All of the Above 4. You are preparing for a trip to Thailand and want to avoid jet lag when you get there. What is a possible supplement you could take prior to your arrival that could help with jet lag? A. Echinacea B. Ginseng C. St. John s Wort D. Melatonin 5. A patient comes to the pharmacy counter with an armful of dietary supplements he wants to start taking. He tells you he is on a blood thinner, warfarin, and asks if it is safe to take the supplements. Which of the following should he not take with warfarin? A. Cranberry B. Ginseng C. Garlic D. All of the above 6. Your friend, a young female with no significant health issues, complains she is always getting urinary tract infections. What is a potential dietary supplement she could try to help reduce the frequency of urinary tract infections? A. Cranberry B. St. John s Wort C. Coenzyme Q-10 D. Melatonin 7. A patient comes in and said he wants to stop finasteride (Proscar ) which he takes to help with BPH symptoms. He is looking for a dietary supplement he could take instead, but he cannot recall the name of it. Which of the following is he most likely inquiring about? A. Cranberry B. Fish Oil C. Saw Palmetto D. Coenzyme Q A friend says she feels like she is starting to develop a cold. She asks you if you know of any supplements that can help with cold symptoms. You recommend to her: A. Coenzyme Q-10 B. Echinacea C. Cranberry D. Ginseng 9. A dietary supplement by definition may contain which of the following: A. An herb B. A vitamin C. A mineral D. An amino acid E. All of the above CPE Instructions: 1. Go to click on Technician tab 2. Scroll down to Pharmacy TEAM Series 2015 and click on Register and Log-In (if this is your first time in CEI s website you will need to set up a quick profile by clicking New To CEI ) 3. Click on the box to select the TEAM Series 2015 and click Register 4. On the Payment Transaction Page, scroll down to Pay With An Access Code and type in the access code given to you by your association and click Continue 5. You can now start the TEAM Series right away by clicking Click Here to Go to Activity. Scroll down to activity and all 10 TEAM articles are within your profile! 6. Whenever you want to go back in and complete a TEAM Series activity, go to Log-In, and click on your Profile. Any questions, please contact Cindy Smith at csmith@gotocei.org or TEAM SERIES 67