Herbs and Supplements: Are They Safe for Transplant Recipients?

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Herbs and Supplements: Are They Safe for Transplant Recipients?

Thursday, May 4, 2023

Presenter: Colleen Timlin, PharmD, BCOP, Hospital at the University of Pennsylvania

Presentation is 47 minutes long with 12 minutes of Q & A.

Summary: Herbal remedies and supplements have become increasingly popular for many medical conditions. This presentation reviews the various risks, potential benefits, and specific cautions that transplant recipients should consider before using these products.

Highlights:

• Dietary supplements do not require FDA approval or regulation and are not tested like pharmaceutical drugs. They often carry deceptive labelling and could result in injury or even death.
• Popular supplements like melatonin, milk thistle, saw palmetto, biotin, turmeric, and fish oil may be beneficial for some patients, but they can cause a variety of side effects and drug interactions that must also be considered.
• Stem cell transplant recipients should be especially cautions about using herbal remedies and supplements because they can interfere with chemotherapy. Because they are often absorbed through the liver, they  can be especially risky for patients with graft-versus-host-disease of the liver.

Key Points:

(04:49): Dietary supplements may be found in many forms such as pills, capsules, tablets, gummies, soft gels, and powders.

(07:25): Supplements can treat vitamin deficiencies and nutritional deficits resulting from cancer treatment.

(08:18): Not everyone needs supplements and traditional food is a better source of needed nutrients.

(16:30): The labelling of supplement ingredients may be incomplete, inaccurate or otherwise deceptive.

(18:20): When supplements are necessary, there are reputable organizations people can consult that set standards or provide seals for verified products.

(20:47): Higher concentrations or mega-doses of supplements are not necessarily better and may interact more strongly with other medications.

(22:32): Substituting supplements for recommended medically proven treatment can be very risky for cancer patients.

(24:11): Taking supplements and medications at the same time may slow their absorption, prolong the time treatments are in the body, and limit the benefits of both treatments.

(31:10): Supplemental vitamin D is popular because it's difficult if not impossible for some to get enough from food. But taking too much vitamin can cause several unwelcome side effects.

(45:17): Transplant patients should avoid herbal medications and supplements in the first 100 days after transplant.

Transcript of Presentation:

Note: In this presentation, when the speaker uses the term stem cell transplants, it includes bone marrow and cord blood transplants as well.

(00:00): [Marla O’Keefe]: Introduction: Welcome to the workshop Herbs and Supplements: Are They Safe for Transplant Recipients? My name is Marla and I will be your moderator for this workshop.

(00:09): It's my pleasure to introduce today's speaker, Dr. Colleen Timlin. Dr. Timlin is a clinical pharmacy specialist in the malignant hematology and hematopoietic cell transplant cellular therapy department of the Hospital of the University of Pennsylvania.

She has published and spoken extensively about management of side effects of transplant and CAR-T cell therapy. Dr. Timlin is an active member of the American Society of Transplantation and Cellular Therapy Pharmacy Specialist Interest Group, the Hematology and Oncology Pharmacy Association, and the American Society of Health System Pharmacists. Please join me in welcoming Dr. Timlin.

(00:56): [Dr. Colleen Timlin]: Overview  of Talk. Thank you so much for the kind introduction. I'm very excited today to be talking to this group about herbs and supplements. Are they safe for transplant recipients?

(01:07): The learning objectives of this presentation: I hope by the end of this workshop that attendees will understand how herbs and supplements can vary in potency and contamination. How herbs and supplements may interact with medications prescribed by a doctor. Popular herbs and supplements that should be avoided by transplant survivors and why. And, how to find reliable information about the safety and effectiveness of particular herbs and supplements.

(01:37): There are 80,000 herb and supplements on the market.I want to disclose that I have no financial disclosures but did want to mention that this presentation will not provide individualized recommendations. I may mention this number a little bit later in the presentation, but in doing some of the research into herbs and supplements for this talk today, a number that I came across is something like 80,000 different herbs and supplements on the market, so, there's a lot to potentially cover. We have a short time to talk about it today, so I'm just highlighting a few of them.

(02:11): One of the things mentioned is that I am a pharmacist at a transplant center and very involved with other pharmacists. And the great thing about being a transplant pharmacist and getting a bone marrow transplant is that we are part of the team. I would recommend that if anyone has individualized questions that they'd like to ask, it's the great thing is that all transplant centers have a pharmacist. You may not have met them before, but they are a resource that's available if you reach out to your providers, and they could help you to get very personalized information.

(02:49): The other thing I wanted to mention, too, is that one of the things that I have excluded from this talk is marijuana and CBD or THC, because a workshop on that topic was presented by another pharmacist earlier in the week.

(03:27): An important question is, what exactly is a supplement?  Congress defined the term dietary supplements in the Dietary Supplement and Health Education Act or DSHEA of 1994. And I'll mention this a few times because it's important in terms of what defines the regulations and how we define supplements going forward.

(03:51): Dietary supplements are ingested products taken by mouth to add or supplement a person’s diet. So, a dietary supplement, "It's a product intended for ingestion that, among other requirements, contains a dietary ingredient intended to supplement the diet." In other words, dietary supplements are products that are ingested and intended to add or supplement the diet. Federal law defines a dietary supplement as, "Products that you take by mouth." So, it could be a tablet, a capsule, a powder, or a liquid. It's made to supplement the diet. It has one or more dietary ingredients, which may include vitamins, minerals, herbs, or other botanicals, amino acids, enzymes, tissues from organs or glands, or extracts of any of these. And they also must be labeled as being a dietary supplement."

(04:40): Botanicals are supplements that contain herbs. On the other hand, herbal supplements, sometimes called botanicals, are a type of dietary supplement that contains one or more herbs.

(04:49): Dietary supplements may be found in many forms such as pills, capsules, tablets, gummies, soft gels, and powders. They can also be in the same form as a conventional food category such as teas or in bars, but only if the product is not represented as a conventional food or as a sole item in the meal or the diet.

(05:15): Plants have been used for medicinal purposes long before recorded history. Ancient Chinese and Egyptian papyrus writings describe medicinal use for plants as early as 3000 BC. And Indigenous cultures used herbs in their healing rituals, while others developed traditional medical systems in which herbal therapies were used.

(05:37): In the early 19th century, when chemical analysis first became available, scientists began to extract and modify the active ingredients from plants. And later, chemists began making their own version of plant compounds. And over time, the use of herbal medicines declined in favor of drugs.

(05:55): Interestingly, I wanted to point out that almost one quarter of pharmaceutical drugs are actually derived from botanicals. So, as being more natural and more organic is becoming popular, it’s interesting that one fourth of the pharmaceutical drugs are derived from the botanicals.

(06:18): Herbal medications are widely used worldwide and are increasingly popular in the U. S. Recently, the World Health Organization estimated that 80% of people worldwide rely on herbal medications for some part of their primary healthcare. One of the countries that uses herbals very much in their care is Germany. And in Germany they have about 600 to 700 plant-based medicines that are available and prescribed by about 70% of German physicians. So, very heavily used in German society.

(06:48): In the past 20 years, in the US, public dissatisfaction with the cost of prescription medications combined with an interest in returning to natural, or organic remedies, has led to a significant increase in herbal medicine use. There are an estimated 80,000, products that are currently on the market. In my practice I probably get at least one question a day from patients discussing herbals, their use, checking to see if it's something that would be safe for them to take with their other current medications.

(07:25): Supplements can treat vitamin deficiencies and nutritional deficits resulting from cancer treatment. Why do people take supplements? Your doctor may prescribe a supplement if you have or may develop a vitamin deficiency caused by treatment. For example, certain cancer therapies weaken bones and can contribute to the development of osteopenia or osteoporosis. In these cases, your doctor may prescribe calcium and vitamin D to support your bone health. In some cases, supplements may also be needed if your cancer treatment makes it difficult for you to get the nutrients that you need from foods such as fruits, vegetables, whole grains and meats.

(08:00): Alternatively, some patients who've had surgery or have part of their digestive tract removed, maybe in the stomach or the intestines, these patients might not be able to absorb certain vitamins or minerals, so they may need to take a supplement to get those nutrients in their diet.

(08:18): Not everyone needs supplements and traditional food is a better source of needed nutrients. One big misconception is that we all need supplements. Really, unless you have a known history of a specific vitamin deficiency or are at risk for one because of your treatment or the cancer itself, it is best to get your nutrients through food.

(08:35): Another misconception is that when you take something, say like a multivitamin, your body will use what it needs and get rid of the rest. In truth, it's better not to introduce supplements into our bodies that we don't need or to overload your body to filter all those things out if they don't need it.

(08:56): Even though dietary supplements can be beneficial, they should not take the place of a variety of foods that are important for a healthy diet. For people diagnosed with cancer and who want to feel better, food is the best source for nutrients.

(09:21): The Food and Drug Administration (FDA) considers vitamins, herbs, and botanicals as food, not drugs. It is important to differentiate the two. Many people incorrectly assume that dietary supplements are tested by the FDA for safety and effectiveness, but unlike drugs, the FDA does not have the authority to approve dietary supplements or their labeling before they are sold to the public. It’s a different process in terms of how they're regulated and the process by which they can come to the market.

(09:59): Dietary supplements do not require FDA approval or control and are not tested like pharmaceutical drugs. While manufacturers must ensure the products are safe and that all the labeling claims that are on a supplement are confirmed through evidence, dietary supplements do not require the FDA approval before they are marketed. Drugs must go through a rigorous process, but it's not the same process for herbals and supplements.

(10:23): The FDA can only act against misbranded, unsafe, or adulterated supplements after they are on the market. So, for drugs, the FDA is heavily involved before a drug gets to market. Whereas, 9with herbals and supplements, they're only involved after the product comes to market. If a product is found to be unsafe or not otherwise in compliance with the law, the FDA can work with the company to bring the product into compliance, or they can recommend it be removed from the market.

(11:03): Unlike herbs and supplements, pharmaceutical drugs are rigorously tested and regulated before reaching the market. Under the 1994 Dietary Supplement Health and Education Act (DSHE), manufacturers of herbs and supplements are not required to provide information to the FDA prior to marketing. This DSHEA eliminated the FDA pre-market review and approval of dietary supplements and also removed the FDA's authority to test dietary supplements. As a result, that rigorous, necessary control that the FDA legally had over prescription products was invalidated or taken away from herbal and supplement products. I want to really emphasize that it's a different process the way that drugs come to market and herbals and supplements come to market.

(11:51): Despite these limitations, though, the regulations that are in place for herbals and supplements do spell out that companies are responsible for ensuring that the dietary supplements they sell are safe and properly labeled.

(12:10): According to the Tufts Center for the Study of Drug Development, the full research, development, and approval process for a new drug product can take anywhere between 12 and 15 years. The investment made by drug manufacturers to get a new drug from the initial research to patients, oftentimes exceeds $2 billion. Only one in a thousand of the compounds that enter the lab testing ever make it to human testing and only a small percentage of those make it to market. The FDA must regulate and approve new prescription drugs before they can be sold to the public.

(12:53): The manufacturer follows a series of important steps through animal studies and clinical trials in humans to ensure a medication is safe, does what it claims to do, and provides a health benefit. Generally, the first step in creating a new medication begins with finding a gene or protein, a target for a medication, that plays a role in a specific disease or medical condition. And this gene then becomes a therapeutic target for the medication.

(13:25): Once this new potential medication is identified, it's tested in a laboratory, and this is done long before it's ever used in humans. Testing is performed first in laboratories and on animals to determine if a drug is safe and it can be used before we use it in humans to understand how it works in people. If the laboratory supports the safety of the medication then it can go on through the clinical trial phase. An application to the FDA is made to start in humans.

(13:59): Very few proposed drugs receive FDA approval and reach the market. And just to think about at each step of the process here that's listed, between the basic science research to FDA approval, that number of drugs starts at about 15,000 and significantly drops down to a very, very small percentage that actually then gets FDA approval.

(14:20): I really wanted to highlight how rigorous this process is, how time-consuming it is, and how, despite such a huge number at that very first step, of potential targets and are things that may be beneficial for treating a disease, that only a very, very small percentage of those are eventually able to be used to treat patients.

(14:51): The drug process is very, very different and as I keep saying, it's very rigorous in terms of the time that's invested, the number of people that are involved, and, the investment financially for the companies to have them go to market.

(15:14): Once approved by the FDA, drugs must be continually monitored for safety and side effects. Once a medication is improved, another crucial step is that drug companies or manufacturers are required to continue to monitor the safety of the drug after it's on the market. This ensures that any serious or rare side effects that may have been missed in the clinical trials are still caught. They're still evaluated. So if there is a safety issue, that medications can be taken off of the market. I really wanted to spend time really honing in  on the process, the science involved, and really the trust in the science in the process.

(15:57): Because they are not FDA approved, supplements may carry deceptive labeling and may cause injury or death. What I consider scary is that the FDA found some deceptive practices that may have occurred with herbals and supplements, because they don't necessarily go through the same testing. So, the FDA has found that what is listed on the label of a dietary supplement may not be what's actually in the product. So, the product may cause injury, death, or other serious effects even when it's used as directed.

(16:30): The labeling of supplement ingredients may be incomplete, inaccurate or otherwise deceptive. For example, some products marketed for weight loss, sexual enhancement or bodybuilding have been found to contain prescription drugs that are not allowed to be in dietary supplements. Or equally as scary, products contained other ingredients that are not listed on the label and some of these ingredients may not be safe. So, despite an herbal or supplement claiming to be what is on the label, sometimes it's not. Actually, sometimes there are more things on it than what is listed. And sometimes the doses that are listed are not exactly what is included. And I'll give an example later in the presentation of one that's been in the news recently.

(17:17): It’s also important, when looking at an herbal or supplement and trying to determine what is in the product, to be cautious of terms like proprietary blend. If a manufacturer isn't willing to share all of the ingredients on the label, you're not really going to know what's in that product.

(17:37): Almost half of supplement labels may be incorrect. A study once used DNA bar coding of over-the-counter supplements and found incorrect labeling on almost half of those included in the study. As an example, in that study, one product was labeled as having St John's Wort, which is an herbal product we'll talk about later. It’s commonly used to treat depression. But the product actually contained senna, which is a non-prescription herbal laxative. So, something completely different than what was on the label. It's important to know what you're putting into your body, so you don't accidentally take something that could have an unexpected or negative impact on your health.

(18:20): When supplements are necessary, there are reputable organizations people can consult that set standards or provide seals for verified products. For those circumstances where it is indicated that you do have a deficiency and need to take a supplement, how do you find a reliable source or a reliable manufacturer? The US Pharmacopeia sets the most widely accepted standards for dietary supplements and there's actually a list of USP verified products that you can find online at quality-supplements.org.

(18:59): You may also find seals from other valid third-party testers or other seals of approval such as NSF International, UL Solutions, and ConsumerLabs. And I put pictures of those up here on the slide, so you can easily identify them when you go into a pharmacy and are looking for a quality product. Some products will create seals to make them look like they're more reputable, but beyond those that are listed here, ignore unknown certifications even if they look official.

(19:35): Dietary supplement labels must include a company contact that has a US address or a domestic phone number for reporting any serious adverse events to the manufacturer, or packer, or distributor so that they can be reached and those complaints may be made. So, that's another way to determine if a manufacturer or a product is a higher quality product.

(20:06): Supplements with the fewest ingredients are preferable. And one of the things that is important in selecting a product is to choose the one that has the fewest ingredients. The fewer ingredients in a product, the better. If you need to take a supplement to address a vitamin deficiency, ideally you want it to contain that ingredient with as little possible beyond that. If you don't need anything extra, you don't need to take anything extra, because there’s a chance that it may be something you don't want to take. So, try to minimize that as much as possible.

(20:47): Higher concentrations or mega-doses of supplements are not necessarily better and may interact more strongly with other medications. So, in thinking about the risks of taking supplements, most supplements have a higher concentration than the same ingredient found in foods. And supplements that you buy from stores or online may differ in important ways from products tested in research studies.

(21:11): What this kind of statement means is that there is research that is done on some ingredients. What's important in those studies is looking at what the doses are, what the diseases are that are studied, because even though the study may show the results in that ingredient, it's important to have the right manufacturer, the quality manufacturer. You want to make sure that you just have that supplement and only that supplement in the product and at the correct dose that they're claiming to be on the label.

(21:52): Some supplements can contain different or mega-doses of the ingredient. It may not be clear on some labels or some bottles how much or how often a supplement should be taken. Oftentimes, when people are taking supplements, they're taking more than one supplement at a time. Sometimes supplements can interact with each other. That's another really important thing. You want to be cautious not to start taking too many supplements at once. Ideally try just do one at a time.

(22:32): Substituting supplements for recommended medically proven treatment can be very risky for cancer patients. Some people don’t trust the pharmaceutical industry or the medical profession and opt to use supplements instead of recommended, medically proven treatment. So, obviously there's a risk outside of taking just that supplement. Patients may also now have the risk of their disease becoming worse during that time if it's not being treated. And potentially, the disease may become more difficult to treat if they later realize that those supplements have failed and they must use a medical treatment. They lost that time to treat the disease when it was a little bit less aggressive or less severe. They delayed it by taking supplements. So, that's one of the risks in taking something that isn't proven to be effective for a particular disease.

(23:26): Supplements can create potentially serious adverse events and side effects.  Adverse events can range from less serious to life-threatening. Some side effects can be rash, fatigue, persistent severe vomiting or diarrhea, difficulty urinating, joint, muscle pain, chest pain or stroke. It's important that even though supplements are easily accessible and they're over the counter, doesn't necessarily mean that they're safe. So, everything should be verified with your pharmacist, with your doctor, to make sure that they are a good quality product, that they're okay to take with the medications that you're taking and that you have somebody review each one before you take it.

(24:11): Taking supplements and medications at the same time may slow their absorption, prolong the time treatments are in the body, and limit the benefits of both treatments. An important organ that breaks down both medications and supplements is your liver. Your liver is the body's filtration system. There are certain parts of your liver called enzymes which break down both medications and herbals. Sometimes the herbals compete with the medications. So, if they're both being broken down at the same time, it slows the way that the drugs get broken down. As a result, the drug may  stay in your system longer than anticipated and potentially cause more side effects.

Your liver function and breaking down medications, it's an important part of your blood system. So, as the medications are broken down, getting them to where they need to go.

(25:31): And your liver is also important as part of your dietary and medication breakdown as well. It's very important and something that, in taking both herbals and medications and breaking down food, can sometimes cause medications to be in the system or even herbals in the system longer than intended. So, use caution.

(25:57): Dietary supplements must be labeled as a dietary supplement. All of us, I believe, are very familiar with the nutrition labels that are found on food, but are you aware that herbals and supplements have labels as well? So, to be a dietary supplement, a product must be labeled as a dietary supplement. The product label must include the actual words, "Dietary supplement." Or, "Equivalent." Or, it can say, "Iron supplement." It can say, "Herbal supplement." And that DSHEA, as we talked about earlier, places dietary supplements in a special category under the general umbrella of food, unless the product meets the definition of a drug. A drug can say it's labeled to treat or prevent a disease.

(26:48): So, similar to the food label that all of us recognize, there's requirements that have been placed on dietary supplements, to include on their label. So, regulations place dietary supplements in a special category under the umbrella of food unless it beats that definition of a drug.

(27:12): Dietary supplements are required to have a supplemental facts label, similar to the one that's shown here on the slide. The supplemental facts panel must list the serving size, the number of servings per container. It must declare each dietary ingredient in the product, the dose of each ingredient. And except for dietary ingredients that are part of that proprietary blend we talked about earlier, it must provide information on the amount of the dietary ingredient per serving as well, too.

(27:55): Serving amounts and percentage of daily value must also be on supplement labels. Depending on the type of ingredient, the amount per serving must be declared as either amount by weight, as a percentage of the daily value, or both, as seen here on this label. Any additional ingredients or any other inactive ingredients must also be listed as part of the dietary supplemental facts label.

(28:20): I warn you to be cautious of products that have proprietary blend in their supplement facts, because we don't know what components may be in that blend. And if a manufacturer isn't willing to share all of the ingredients on a label, it's difficult for people in the medical field like physicians, or myself, to understand what's really in a product, to be able to check it to see if it is something that's safe to take with your medications or something that's safe to take maybe with any of the medical diagnoses that you have.

(28:59): Supplements labels must contain an FDA approved acknowledgement that they have not been FDA evaluated and are not intended to treat any disease. So, one of the other really important parts of a label is that, for a supplement, it's required that the label bears the disclaimer that, "This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease." They cannot make a claim for supplements or herbs, that they prevent a disease, that they diagnose a disease, that they treat a disease, because there's no basis for saying that. The only way that you can say something can prevent or treat a disease is if there are research studies and clinical trials in which those things are shown to be true.

(29:55): So, some of the supplements that I'm going to focus on today are listed here on this list. As I alluded to earlier, the number of supplements on the market is astronomical, and so, even narrowing it down to these few, certainly I know is difficult since there are so, so many out there. I'm focusing even within this group as well, too, some more than others, based on some of the questions that I get from people and also, too, to try to focus on maybe ones that do have more information about them than others.

(30:40): So, one that I get questions about very often is vitamin D. So, I'm going to go into detail with this one and maybe some of the others, to talk about what it is in more depth. So, vitamin D promotes calcium absorption in the body and having enough vitamin D is essential to health and wellbeing, offering the promise of protecting bones and preventing bone disease such as osteoporosis.

(31:10): Supplemental vitamin D is popular because it's difficult, if not impossible for some to get enough vitamin D from food. So, the Centers for Disease Control and Prevention (CDC) notes that, "Our bodies also make vitamin D when bare skin is exposed to the direct sunlight. But increased time indoors and widespread use of sunblock, has been really promoted recently to prevent skin aging and skin cancer. Staying indoors more, using more sunscreen has minimized the amount of vitamin D that many of us get from sun exposure." So, vitamin D is something that we can measure and check and see what the levels are in the body.

(32:03): Vitamin D supplements are a little bit of a tricky topic and sometimes it seems that guidelines and research contradict each other. So, for example, when healthy pre and postmenopausal women take vitamin D and the doses are really small, just at 400 international units, in the clinical trials it hasn't been shown to necessarily prevent them from breaking bones. So one might think, "Well, if a little doesn't work, should I take higher?" But higher doses aren't necessarily a better option either.

(32:38): Taking too much vitamin can cause several unwelcome side effects. So, for those taking too high or having high vitamin D blood levels, it can actually cause an increase in calcium absorption. People can get more side effects from taking too much vitamin D, such as those listed here. Muscle pain, mood disorders, abdominal pain, kidney stones. It also could even raise the risk of heart attack and stroke. So more is not necessarily better when it comes to supplements.

(33:08): Vitamin D supplements can benefit several categories of people including older adults. That being said, though, vitamin D supplements, it's something we can measure. It's something that we can see that there's a deficit. Vitamin D supplements may benefit certain people. So, those at risk or have a deficiency, those individuals with darker skin, certain health conditions in older patients. The most recent American Geriatric Society statement suggests that people older than 65 can help reduce the risk of fractures and falls by supplementing their diet with vitamin D, in addition to calcium rich foods. Anyone can bolster their vitamin D also, too, in the sun if they don't have sunblock. Highlighting some of the possible side effects here and the risks to avoid for patients with kidney stones, kidney disease, or high blood calcium levels as well.

(34:10): Melatonin gummies have been found to be deceptively labelled about doses and other ingredients. I'm going to go through these next ones a little bit faster to be respectful of our time. So, the next one is one that's been in the news a lot lately. There was recently a warning last month from pediatricians in relation to melatonin gummies. So, GMO, which is a medical journal, researchers found that some of these gummies contain higher doses of melatonin than are listed on the label. Some products even contained less than advertised, or high doses of other ingredients such as CBD.

(34:49): So, of the 25 melatonin gummies analyzed, about 90% were inaccurately labeled and only 3, or 12%, contained the amount of melatonin that it said was on the label. I wanted to bring it up since it was something in the news recently. Despite melatonin being a hormone that the body produces, and that plays a role in sleep, it's released by the brain in response to darkness.

It's commonly used as an over-the-counter sleep aid. It helps your body set your sleep time or when you should fall asleep versus it being something that actually makes you fall asleep. It's not something that you wake up in the middle of the night and take to go back to sleep. Be cautious with gummy products.

(36:10): Melatonin can also create grogginess in the morning.  The other thing that's important about melatonin is that sometimes you can see a hangover effect or grogginess in the morning. So, it can have the opposite effect of what you want, of being rested and alert for the day. If melatonin is something prescribed, the doses are typically on the lower end, so a 3 to 5 milligrams versus some supplements on the market that have up to 20 milligrams.

(36:35): Milk thistle has a lot of side effects and should be used with caution. Milk thistle is reported to be used in liver damage and patients with Alzheimer's disease. Some food sources where you could derive milk thistle as opposed to supplements are in the seed, pod, or fruit of the milk thistle. This medication does have a lot of drug interactions because of the way it breaks down in the liver. Some of the side effects actually may be an increase in those liver tests, or an upset stomach. Very importantly, if you're considering starting this, ask your doctor or ask your pharmacist, because milk thistle does have a lot of drug interactions.

(37:21): Saw palmetto can also have serious side effects and must be used with caution. Saw palmetto is used for patients with prostate cancer, urination, BPH, anti-inflammatory, reportedly. Some food sources that you may find naturally saw palmetto are in the fruit of a dwarf palm that grows in the coastal lands of North America, the West Indies, and Mediterranean countries.

(37:45): Some of the drug interactions the supplement may have are with blood thinners and anti-inflammatory drugs such as NSAIDs. Some of the side effects that you may experience if you're on saw palmetto include upset stomach, tiredness, headache, decreased libido, a runny nose, or bleeding time. Be very cautious with this and make sure you discuss with your pharmacist or your physician, because it does have many drug interactions, especially really important ones like those blood thinners.

(38:19): Biotin can be beneficial in preventing hair loss but it is also present in many foods. Another one I get a question on a lot is biotin. So, biotin's an essential vitamin that helps with the production of keratin, which is a protein that's used in the formation of nails, skin, and hair. What's important with biotin is that the studies have shown its benefit in hair loss. It's important to know there's a difference between something that helps promote hair growth and something that helps prevent hair loss. For right now, there isn't enough research that states that it can help hair grow, but it's been found to be beneficial in patients to prevent hair loss.

(39:04): So, if you want to incorporate biotin into your diet, it's present in many foods including beef, liver, eggs, salmon, pork chops, sweet potatoes, almonds, those listed here. Some of the possible interactions to note, which are important, are certain lab tests. Be sure to mention that you are taking biotin whenever you’re asked which drugs you're on, so the that it doesn't interfere with any of the lab tests for those drugs. It may cause interference, so let your providers know if you're going through any diagnostic procedures, or to make sure that there's not an incorrect response to therapy.

(39:52): Turmeric has many interactions and should preferably be gotten through food intake. Turmeric is another one important to talk about. Reported use is in cancer, infections, inflammation, and joint pain. Some of the food sources that you can find it in, sometimes cooking in curries include turmeric. This has, as you can see, a huge list of possible interactions. It's generally preferable to use turmeric in your food and tea, because it's in much lower doses and tends to not have the possible drug interactions to the same level that the supplements do.

(40:31): Glucosamine. I'll go over this one again really quickly. I'll let the group read this one, to focus on some of the other ones I have listed here, before the end of our presentation.

(40:45): Garlic is another that is reported here for the use of cancer, heart disease, infections, that I recommend through food sources such as the bulb or clove of the garlic plant. Note: if you do take a garlic supplement,  it should be stopped one to two weeks before surgery, because it may increase your potential to have a bleeding complication after the surgery.

(41:12): Probiotics can cause infection and should be avoided by people with graft-versus-host-disease (GVHD). Another popular one are probiotics, reportedly taken for digestion, for bowel function. Probiotics can be found in yogurt, miso, tempeh, pickled vegetable, here. It does have a lot of interactions potentially when you're on therapy for GVHD, because it affects your gut flora. Oftentimes people have GVHD in the gut. So, it's something that we try to avoid for people who have GVHD. Also, it can potentially cause infection. We recommend that patients that are on immunosuppression avoid it, if you're neutropenic avoid it, or if you're on treatment for GVHD.

(41:56): Fish oil has many interactions and can decrease the efficacy of some chemotherapy. Some information here on fish oil that I'll include.

St. John's Wort. The one message I wanted to give about this was that it has been looked at for patients with depression, anxiety, fatigue, sleep, menopause, and to heal wounds. And the one flag that I certainly think of with this medication is that this has a lot of drug interactions, as you can see listed here, and really important ones. So, your blood thinners, your cholesterol medications. So, to use with caution and certainly make sure that you discuss with your providers because it can decrease the efficacy of some chemotherapy. So, stop it at least one week before surgery or chemotherapy.

(42:49): The maker of Prevagen® has been charged with false advertising. I'll go through this one quickly and I can answer any questions if they come up about it, because this is another one I often get questions about is apoaequorin. So, this is the main ingredient in the dietary supplement Prevagen®. So, just be cautious that with this product, This supplement maker had been charged with false advertising. Be cautious with supplements and them making claims on efficacy.

(43:24): I wanted to be sure to include this list of herbals to avoid for patients after transplant because of the risk of drug interactions with a lot of the medications after transplant. Before you consider any of these, you should absolutely talk to your provider to make sure, because the risk of side effects.

(43:51): Stem cell transplant recipients should be especially cautions about using herbals and supplements because they can interfere with chemotherapy. So, specifically, concerns for our stem cell transplant patients when it comes to herbals and supplements, number one is that they may interact with chemotherapy. And when I say chemotherapy it may be the chemotherapy that you're getting prior to your transplant. It may be some of the things used for maintenance after, or maybe even the immunosuppression. So, it can make it less effective, it could potentially make the side effects more toxic. Try to avoid the use while you're on treatment. But if you do have interest, reach out to your pharmacist, reach out to the pharmacist at your transplant center, or your physician, and they can help guide you.

(44:35): Herbals and supplements can be especially risky for patients with graft-versus-host-disease of the liver. The drug interactions. The supplement reactions. Another really big issue is that graft-versus-host-disease often occurs in the liver. This is also where a lot of the herbals and supplements are broken down. Sometimes herbals and supplements can be confusing and cause rises in those liver numbers that may make us think that graft-versus-host-disease in the liver is there when it's not or may be worse than what we truly think it is. Try to avoid using supplements if you have graft-versus-host-disease because of those changes to the liver and organ function.

(45:17): Transplant patients should avoid herbal medications and supplements in the first 100 days after transplant. I also think it's very important for our transplant patients, if you are considering using supplements, that timing is really important. So, definitely, we recommend avoiding [them] in the first 100 days after transplant, since your body's undergoing so many changes. To try to avoid them while you're on immunosuppression, because we don't want to decrease the efficacy and cause any rejection because of the drug interactions. Like we talked about on the last slide, avoid them if you have any graft-versus-host-disease as well, because it can make it really confusing if your liver numbers bump.

(45:58): When using herbal medications and supplements, start only one new product at a time. Start only one new product at a time. So, don’t start three different herbals, because we don't know how each of them mix with each other.

(46:11): There is a new FDA dietary supplement ingredient directory that is available online for the public. Some additional resources I wanted to list here and a big one, actually, that came out as I was doing this presentation is that back in March of this year, the FDA unveiled a new dietary supplement ingredient directory, which is a really important resource for consumers. This is a webpage that's intended to help the public stay informed about the ingredients in dietary supplements. So, consumers can use the directory, they can look up ingredients used in the products marketed as dietary supplements. You can find out what the FDA has said about the ingredient, whether the agency's taken any action against the ingredient.

(46:51): It's really a way to inform the public, a way to be able to look up what's in the supplement and see if there are any FDA warnings against that supplement. The FDA has a lot of really, really great resources on their website. I encourage people to look at it you have any questions or interests. Thank you for joining in today and I’ll now address some of the questions that we have here.

Question and Answer Session

(47:28): [Marla O’Keefe]: Thank you, Dr. Timlin, for this excellent presentation. We will now begin the Q&A. “Do you consider collagen a supplement? I'm considering taking it to improve skin elasticity."

(47:54): [Dr. Colleen Timlin]: Well, that's a really great question. So, collagen can be something found in food or it can be something that is found as a separate supplement. So, collagen, if you're able to get it in your diet, that would probably be the first place that I would recommend going to in getting it.

Otherwise, in thinking about supplements, there isn't a lot of great data about what product to use, what doses to use. So, it's a little bit of the wild, wild west. I think it does have potential and would definitely say yes if you're able to incorporate it into your diet.

(48:50): [Marla O’Keefe]: "What is the maximum amount of vitamin C I should take post-CAR-T? What is the maximum a person in good health should be taking?"

(49:02): [Dr. Colleen Timlin]: Well, that's also a really, really good question. We don't really know, we don't have a good idea what that maximum number is. And we don't really know if there's a reason that you need to take that really high maximum amount after CAR-T.

There are a lot of ways that people take vitamin C. Some people take it at those really high doses in IV form. That's not something that we recommend at our program. Usually we recommend just taking vitamin C or a multivitamin to help supplement the diet. There's no information that you really need those mega, super doses that are seen in some of the supplements. We do get very nervous if you're thinking about doing the IV supplements, because we don't want anybody piercing the skin or putting something into your vein that could be dangerous and higher risk for causing an infection. So, thank you for that question.

(50:26): [Marla O’Keefe]: "Is digestive enzyme safe to take after BMT?"

(50:36): [Dr. Colleen Timlin]: So, digestive enzymes, there's lots of different ones that you could possibly take. There are some people that need that help. So, things like lactase, you may become lactose intolerant after transplant. That is something very commonly seen. It's also more commonly seen as we age. So, those are safe supplements to take, especially if it's causing gas or diarrhea, things that may be confused with GVHD symptoms.

(51:22): There are  things called pancreatic enzymes. For people who have graft-versus-host-disease in their pancreas or have difficulty breaking down fats, those are also dietary enzymes that are recommended. So, those are all really great things that may be appropriate . I definitely encourage you to talk to your providers if that's something that you have an interest in, or having some of those symptoms that you'd like to address with the dietary enzymes.

(51:57): [Marla O’Keefe]: Thank you. "I have read that vit K2 can be useful in directing calcium to the bones. Do you agree with this opinion?"

(52:10): [Dr. Colleen Timlin]: Wow, Congratulations, I haven't heard of that one in my research, that specifically is vitamin K2. So, that would be one that I would actually have to look into and learn a little bit more as well. So, on the safe side, if you do have an interest in taking that, contact the pharmacist at your transplant center and they might be able to give you things that are specific and can look at your medications and see as well, too. So, you picked one of those 80,000 that I didn't know, so thank you for teaching me something new today, too.

(52:58): [Marla O’Keefe]: It was stump the expert today.

(53:01): [Dr. Colleen Timlin]: Done a great job.

(53:03): [Marla O’Keefe]: The next question is, "You listed vitamin D interaction with atorvastatin. Please explain.

(53:13): [Dr. Colleen Timlin]: Sure. So, vitamin D is listed as having a drug interaction with the atorvastatin. So, I there are certain statins, based on the way that your body breaks them down, that are more prone to drug interactions than others. So, atorvastatin is one that is known to have a little bit more drug interactions than others.

(53:47): You might be able to take another statin. So, other names are pravastatin or Crestor is a brand name of another medication that are in that class but tend to have less drug interactions. That is a possibility if you are on atorvastatin and potentially either considering or on vitamin D. So, that's another good question.

(54:20): [Marla O’Keefe]: Thank you. I'm going to combine these two. Someone wants to know, "How do you know if a supplement manufacturer is legitimate?" And someone had asked, "Vitamins and supplements that are sold at Costco and Sam's Club, are they okay to trust?"

(54:39): [Dr. Colleen Timlin]: Yeah. So, that's a really good question. In thinking about supplements, if you go and look at those slides a little bit earlier that have those seals of approval, the big one that's important is the USP seal. Those aren't always necessarily the ones that are sold at Costco. One of the brands that is on that list that has it is Nature's Made vitamins. Those would be a specific brand versus a Costco brand or versus a CVS brand.

(55:24): They might be a little bit more expensive than say, the CVS or the Costco brand, but you know that that company has sent their product to the USP to get verified that it's the right supplement in there, it's the right dose that they're claiming to be on it. It's a way t to show the integrity or the honesty of the company.

(55:53): If those aren't available, big companies like Costco or big companies like CVS, also have their reputation on the line. While it does take money and investment to get that USP seal, it's about establishing trust with a supplement. Financially there's a lot going on after transplant, and the vitamins may be one area that you can cut back on. I aways recommend taking a quality product, but if you can't have a quality product, I would certainly take a Costco or a name brand versus something you just order on the internet that you're not sure where it's coming from. So, I would probably, personally prefer that approach versus the online approach.

(56:50): [Marla O’Keefe]: Great. Thank you. And this will have to be our last question. I'm going to combine this one as well. This person asks, "If a prebiotic and a probiotic are safe for one year after BMT and if you can use ginseng after chemo for tiredness?"

(57:11): [Dr. Colleen Timlin]: So, those are great questions. So, one year after transplant is an important milestone. Prebiotics and postbiotics, the caveat or the thing that would change my mind is whether or not at that point you have graft-versus-host-disease or if you're on immunosuppression.

(57:35): If you say yes to either one of those things, if you do have graft-versus-host-disease or if you are on immunosuppression, I would avoid any probiotics or prebiotics, because those are actually live bacteria that you can be putting into your stomach. I tend to prefer dietary supplements such as yogurt cultures and eating those versus the supplements at that point.

(58:07): And then, the second question was ginger with chemotherapy. Ginger is definitely one of those herbals that has been used in traditional Chinese medicine and has been used for nausea. Where I've found people have the most success with ginger is actually in taking it as a lozenge, so people can sometimes drink ginger ale as well, too. And that's thought that it can help settle the stomach. Because ginger has been around so long, it doesn't have these new clinical trials that prove it to be that way, but like I said, in what I see in our patient population is that ginger in the lozenges are helpful, or ginger ale can be as well, too, versus taking a pill or a capsule of the ginger.

(59:14): [Marla O’Keefe]: Closing. Okay. Dr. Timlin, thank you so much for that very comprehensive presentation. On behalf of BMT InfoNet and our partners, I'd like to thank Dr. Timlin for this very helpful presentation. And thank you, the audience, for your excellent questions.