Herbs and Supplements: Are They Safe? Do They Work?

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Herbs and Supplements: Are They Safe? Do They Work?

Thursday, April 22, 2021

Presenter: Maggie McCallen PharmD, BCOP, Clinical Pharmacy Specialist Hematology/Oncology, Mayo Clinic Arizona

Presentation is 39 minutes long with 20 minutes of Q & A.

Summary:  Herbs and supplements have become popular with the public as well as cancer patients. Because they are unregulated, however, their safety and efficacy are difficult to judge. This presentation reviews the most common herbs and supplements and summarizes what is known about their benefits and risks for transplant recipients.

Highlights:

• Herbs and supplements are not regulated by the Food and Drug Administration (FDA). While prescription drugs must be proven safe before they are approved by the FDA for market, herbs and supplements are assumed to be safe, and only receive FDA scrutiny if adverse side effects are reported.
• Certain herbs and supplements can cause risky side effects for stem cell transplant recipients. Some affect how the liver metabolizes prescription drugs and may make the prescription drug less effective.
• Just because a product is natural does not mean it is safe, and more of an herb or supplement is not necessarily better. Mega-dosing should be avoided.

Key Points:

(04:36) Reported adverse effects of herbs and supplements have dramatically increased over the last ten years.

06:44) Herbal supplement labels are not always accurate and global supply chains complicate the issue. Finding a reputable source for such products is essential.

(08:00) Supplements can alter the effectiveness of prescription medications and affect underlying disease states.

(11:16) Fewer ingredients are preferable in herbal products. Fillers and “proprietary blends” should be avoided whenever possible.

(15:32) Turmeric is an antioxidant that can reduce the effectiveness of chemotherapy by protecting cancer cells along with healthy cells.

(17:45) Omega-3 medications should be avoided for patients on anticoagulation medications because it can increase the risk of bleeding.

(21:06) Glucosamine is a generally safe supplement but should still be avoided until day 100 posttransplant.

(22:22) Garlic supplements can affect bleeding rate and reduce the effectiveness of cyclosporine. It’s not recommended before or after transplant.

(26:43) St. John’s Wort has an extensive list of drug interactions and can reduce the effectiveness of other important medications.

(32:01) Check labels for quality supplements and USP or USP-NF endorsements. These provide some measure of the quality, strength, and purity of supplements.

Transcript of Presentation:

(00:00) [Sue Stewart]     Introduction. Hello, and welcome to this workshop, Herbs and Supplements: Are They Safe? Do They Work? My name is Sue Stewart. I'm the Executive Director of BMT InfoNet and I'll be your moderator for today.

(00:13) Let me introduce our speaker, Maggie McCallen. Ms. McCallen is a Clinical Pharmacy Specialist and a Pharmacy Instructor at Mayo Clinic of Phoenix, Arizona. For the past 16 years, she's worked with oncology and stem cell transplantation. Dr. McCallen is knowledgeable about how herbs and supplements can interact with prescription drugs that transplant patients may be taking. She strives to educate and provide optimal care to patients. Please join me in welcoming what I think will be a wonderful presentation by Maggie McCallen.

(00:55) [Maggie McCallen]     Overview of talk.  Hi, and thank you for having me here today to talk about herbs and supplements. I have been a pharmacist for a total of almost 20 years now, and I can tell you that the use and questions have increased exponentially in recent years regarding herbals and supplements. It's great because it's becoming part of the conversation with healthcare providers and at least everybody's thinking about what interactions and "How can this affect me?" and looking for new ways to maybe help themselves feel a little bit better too.

(01:27) So to get started today, the learning objectives. We're going to discuss what to look for when looking at supplements, review some drug and disease interaction considerations and then, I will go through and assess some popular supplements that I've been asked about the most.

(01:44) So just to get started... Sorry. I think there was supposed to be a survey question. Sorry.

(02:01) [Sue Stewart]      Yes. I think the operator is pushing out the survey question right now.

(02:20) [Maggie McCallen]     So the question that I wanted to ask was just to see how many people are currently taking herbal or dietary supplements. I believe that will take just about a minute to get some of those results in.

(02:32) One fourth of adult patients use dietary supplements along with prescription medications. So, there was a study in adult patients in the United States, and about 25% of adults in the US were using a dietary supplement at the same time as using a prescription medication. So, it is an important consideration to take into as you guys are looking adding herbal supplements or dietary supplements into your program with the prescription medications also.

(03:20) [Maggie McCallen]      Herbs and supplements are everything not considered a medication. Okay. So, moving on. The first thing that I wanted to talk about is the difference between dietary supplements and prescription medications. So when talking about herbs and supplements, they encompass everything that's not considered a medication. These are all your vitamins, minerals, herbals, extracts and so on.

(03:45) Herbs and supplements are considered safe till proven otherwise but reporting adverse effects is problematic. So, one major difference, and I can't stress this enough, is that dietary supplements are considered safe until proven unsafe. They don't have to go through any clinical trials. They aren't approved by the FDA. Whatever is in the bottle is considered safe unless someone has an adverse effect and reports it. There is nothing that requires a customer to report an unexpected side effect, unlike with prescription medications where the medical providers have to report all the adverse effects that occur. Sometimes, it's even hard to figure out how to report adverse effects related to a dietary supplement, but once it is reported, then the FDA will look into the product and determine if it's safe to continue on the market or if it should be withdrawn from the market. Sometimes, this can, obviously, be too late because an adverse effect has already occurred.

(04:36) Reported adverse effects have dramatically increased over ten years. In 2010, there were 1009 reports of adverse events with supplements. In 2020, there were almost five times that with 4822 reports of adverse effects with supplements. Whether the increase is due to better reporting or the increased use of supplements is probably debatable, but just know that there are adverse events that occur and are reported on an ongoing basis.

(05:03) Prescription medications, by contrast, are considered unsafe until proven safe. The difference with the prescription medications is, before anybody is allowed to even take a prescription medication, they have to go through rigorous testing to be proven safe and effective before they're able to be produced and brought to market.

(05:18) So, herbal supplements are considered safe until proven unsafe and prescription medications are considered unsafe until proven safe.

(05:28) Efficacy of supplements is hard to establish. Throughout the talk, you'll probably hear me speak more to the safety than the efficacy, and this because efficacy is hard to establish outside of controlled trials, which are unfortunately not conducted routinely for supplements. Also, to keep in mind though when thinking about efficacy, is that what works for one person may not work for the next. So in summary, prescriptions have to be proven safe and supplements [are assumed to be safe] before coming to market.

(05:59) Supplement safety is difficult to evaluate for several reasons. Since the FDA doesn't regulate supplements before they can come to market, there can also be manufacturing issues with the product that makes them unsafe to take. Many supplements have very clean safety histories and most manufacturers are very careful about their claims, including the labeling and the ingredients. However, not all of them are, and there are always going to be companies that put profit before safety.

(06:22) Sometimes this is not even the manufacturer's fault, but could be the supplier or grower of the herbal product too. They could substitute less expensive or different parts of the plants to supply the manufacturer. Since most supplements are available in a global market, versus restricted to a particular country, it can be hard for a company to ensure what they are putting in the product is the appropriate thing.

(06:44) Herbal supplement labels are not always accurate so finding a reputable source is important. In 2013, there were researchers in Canada that published a report. They analyzed 44 supplements labeled as containing a single herb. Using DNA analysis, they found that less than half of those supplements that were supposed to contain just one herb, less than half of them even contained the herb that was on the label, while more than half of those supplements contained additional ingredients that weren't listed on the label. So just know that when you're looking at these products, what they say is not always what's in there. And so, you want to make sure to find a reputable source for the herbal supplements.

(07:19) Global supply chains add further complications. Some of the herbal supplements are even found to contain prescription drugs, since it is the global market versus only manufactured in the United States, and some of the medications that we have in the United States are considered over the counter. In other countries, they can mix them into their meds. There were a few that were marketed for prostate health and they contained the prescription drug terazosin. And there were weight loss supplements containing sibutramine, which was actually a prescription medication in the United States, but then it was recalled. So, these are all things that you want to take into consideration when you're looking to buy a supplement.

(08:00) Supplements can alter the effectiveness of prescription medications and affect disease states. So next, if we assume that we have a great supplement with a great manufacturer and everything in it is correct, then the next thing that concerns us is what we're going to talk about today: what is a supplement going to do to the medications that you're already on? Is it going to affect any other disease states or any of your organs?

 (08:18): For example, skin: some supplements can cause rashes. Some cause sensitivity to sunlight. These can affect what the medications that you're already on, or compound the effects some of your current medications probably cause some sensitivity to. Or another example is, your GI tract. Your stomach can be more sensitive after transplant, and some of these supplements can add to nausea, diarrhea, constipation, all side effects that may be worse in the stem cell transplant patient versus in your standard population.

(08:51) Effects on the liver are especially important; it is where the majority of drug interactions occur. Speaking of organs, one of the major organs that we are the most concerned about is the liver. This is probably the single most important organ when it comes to medications and supplements, other than maybe your stomach for absorption. The liver is the powerhouse of filtration. Many prescription and non-prescription medications need to be filtered through the liver to work properly. Some enzymes in the liver work to convert medications into their active components. Others works to convert medications for elimination. The liver also filters your blood, getting rid of anything it might not need, like the damaged or old red blood cells. The liver produces the factors needed to help your body clot when you have a bleed. And in addition, the liver helps to break down all the food that you inject. It metabolizes all the fat, protein, carbohydrates that you take in.

(09:41) Because so much goes through your liver and those enzymes work so hard, it's important to look at the liver in regards to supplements, since some supplements may increase or decrease the activity of these enzymes. The liver is also where the majority of drug interactions take place. So if a supplement affects your liver, it may affect a lot of things. If you find yourself looking up information on a particular supplement, I suggest paying close attention to anything pertaining to the liver.

(10:09) Supplement labels should be read and interpreted carefully. When looking at the supplements, you always want to read what's on the label. On the back of the label, you will find the supplement facts. These are required by law to be on each product. If they don't have a supplement fact label, it's considered misbranding. So, don't buy a supplement without the facts label.

(10:27) When looking at the label, you will see the manufacturer's recommended serving size and how many servings in each container. You will also see what is in the product individually listed and the amount of each substance that is in each serving. Here, I would like to point out to watch the serving size. If the serving size is two tablets, it will usually list the ingredients per serving, not necessarily per tablet.

(10:49) In addition, if it is a substance that has a daily dietary recommended value, there will be a percentage in the percent daily values column. Most of your vitamins and minerals will have a percent daily value. Most of your herbal products will not. It's a recommended daily value for a reason. You rarely need thousands or hundreds of times what is the daily recommended value is. And most of the time, your body will just excrete the excess.

(11:16) Fewer ingredients are preferable in herbal products. Herbal products may have just one ingredient or they have many. In general, you want to look for something with the least amount of ingredients and that contains the herbal that you want. Some products will say what part of the plant they used in their blend since some parts of the plants can have different effects. The roots, the leaves, the flowers: they can all do different things sometimes.

(11:37) There are also things outside of the supplement facts box listed as other ingredients. These are usually the fillers that help to get them into the tablet shape or make them taste better. Ideally, they are not the active part of the supplement and you want as few of them as possible.

(11:54) In general also, you want to avoid terms like "proprietary blend". Manufacturers use this term to hide other ingredients and they often contain lower quality ingredients. It's best if the manufacturer is straightforward in listing all of the ingredients or what they use.

(12:11) Dietary supplements are required to have a FDA disclaimer.  In addition, each dietary supplement has to contain this statement: "These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease." The herbal supplements are not allowed to speak to treating or curing any disease.

(12:35) So next, this slide shows what supplements we're going to discuss in a little bit more detail. These are the supplements that I've been asked about the most, and so I tried to pick them out as the most popular ones to talk about.

(12:48) Transplant recipients must be cautious using probiotics because they can promote infections in immunocompromised patients. Starting with probiotics: this one could be one of the most controversial ones too. There are many, many different probiotic products out there, but at their basis, they all consist of living bacteria or yeast that are non-pathogenic. This means that they are supposed to be non-disease causing bacteria or yeast even though they are alive, which means, and the standard population, when you're not immunocompromised, most people can handle these without problems. Transplant patients, however, have to be more cautious when using them. In general, the probiotics are taken to restore the gut flora. The gut usually gets torn up after stem cell transplant or even chemotherapy in general. Or sometimes, when you're using antibiotics, you lose all of the good gut bacteria along with the beneficial effects from your chemotherapy and antibiotics.

(13:50) Probiotics, in general, have very few drug interactions. They may rarely increase your liver enzymes, but it's not usually a big concern. The biggest problem that we are concerned about in the transplant patients are infections. The immune system, during and after transplant, may not be completely intact. This is an area that is still being researched for stem cell transplants. There are multiple ongoing studies regarding the gut microbiota or the gut flora, the gut bacteria, and its importance in the stem cell transplant patients. However, they also know that when you have mucositis, where your gut is inflamed and not happy, that bacteria can move from the gut into the bloodstream and cause infection in the stem cell transplant patient. There have been studies showing one of the supplements, saccharomyces, has caused infection in immunosuppressed patients and there have been incidents also where opening the capsules for the saccharomyces has caused central lines to be infected. We do use those with caution.

(14:52) Discussions with your healthcare provider is important before using probiotics. At the end of the day, if you're an autologous transplant patient who has recovered your white blood cells and your stomach is not inflamed, they are probably safe to take. If you're an allo transplant patient and on any immunosuppression, it really needs to be a discussion with your healthcare provider. Some providers are very supportive of them and like them and others will avoid them at all costs, and it's a very individual thing, along with your provider for whether they are beneficial or not. Hopefully as we do more research into this area, we'll get some better answers and be able to give you some better advice going forward because they are doing a lot of research in this area currently.

(15:32) Turmeric is an antioxidant that can reduce the effectiveness of chemotherapy. The next herbal supplement that I feel like has popped up in recent years even though it’s been around for centuries is turmeric or curcumin. Curcumin is a powerful antioxidant. Antioxidants are the things that protect your cells from damage, but what if they protect the wrong cells?

(15:53) Chemotherapy works by attacking cancer cells. If you have an antioxidant that protect the tumor cell and makes the chemotherapy less effective, then you're taking a risk that the chemotherapy won't work. So if you're actively on any chemotherapy, don't take turmeric supplements.

(16:10) Turmeric can interact with over the counter and transplant medications so consulting with medical providers is imperative before use. Turmeric is also said to have anti-inflammatory properties. These can reduce pain and swelling. However, these can also interact with other medications that do the same thing, such as aspirin, ibuprofen, acetaminophen, all of those can also be affected by the curcumin or turmeric.

(16:29) Turmeric is also metabolized by the liver and inhibits those enzymes that are necessary to process medications. It does have known interactions with tacrolimus, some anticoagulants and some blood pressure medication. So if you are taking other prescription medication, it's very imperative that you have someone look into whether they are going to interact with the curcumin. You also want to watch out for any liver side effects that might occur from it too, such as hepatitis. Sometimes, you also get some sun sensitivity and rashes from the turmeric also.

(17:06) Turmeric in cooking is generally safer. Turmeric used in cooking is a different story. So in general, if you're using it in cooking or teas, it's okay to continue to eat it in your normal amount. You just don't want to supplement more than what you would do on a daily basis if you were not on any medications or if you were just living your normal life. You don't want to add on additional turmeric to that. The supplements tend to be a lot more potent than what's used in cooking or teas, and so we worry more about the supplements than we do about what is in your normal food.

(17:45) Omega-3 medication should be avoided for patients on anticoagulation medications, active chemotherapy, or within 100 days of transplant. Next are Omega-3. These are fatty acids. Mainly they come from fish oil, but they can be nuts and seeds, too, like flax seeds or linseed, walnuts, et cetera. Omega-3s can be taken for depression. However, most commonly, they are usually used to lower cholesterol and reduce the risk of heart attacks. There are some questionable findings on preventing cancer and diabetic neuropathy, which is the pain in your hands and feet too. The biggest complaint that people have when taking Omega-3 is it has a fishy smell or taste. They do have supplements that reduce that side effect of the fishy smell.

(18:23) In general, for the stem cell transplant patient, we try to avoid Omega-3s for the first 100 days after transplant. High dose Omega-3s greater than two to three grams a day can affect your bleeding time. You need to use caution if you're on any anticoagulation or on active chemotherapy treatment. Omega-3s can affect your bone marrow and how it actually produces that blood. There have been studies that they are doing in mice and humans to see exactly what those effects are, and it hasn't all been decided yet for whether they are harmful or have no effect on them.

(19:03) So, Omega-3s are probably okay if you're off of your immune suppression or not on immune suppression and if you're not currently taking any blood thinners or steroids. And then, usually we would wait until you're at least 100 days out from transplant also.

(19:23) Elderberry can pose risks to transplant patients; check with your medical provider first. Elderberry: this one I hadn't even heard of until the last couple of years, and most recently in the last year because of its antiviral properties. There are small studies that have looked at it as reducing cold and flu symptoms, and I think it came up a lot lately with the last year and some of those viruses out there. So, there's nothing specifically that has been looked at for Elderberry and the stem cell transplant patient, but one thing to watch out for if you're looking at taking the Elderberry supplements is that raw or unripe elderberries or the elderberry leaves, stems and bark all contain cyanogenic glycosides. These are things that have cyanide-like properties and can actually cyanide toxicity. So, it's important here that you make sure you have a reputable source of the elderberry supplement.

(20:16) In addition to the antiviral properties, elderberry supplements have also been used to promote urination, but they can have additive effects if you are already on a diuretic or a water pill. In addition, they can have some laxative effects too. So if you already have loose stools, you probably don't want to supplement with elderberry on top of it. And of course, in this time with the COVID virus running rampant, you want to always get checked out first if you think you have a cold. You would want to go to your medical provider first and don't just start taking elderberry in the hopes of staving off anything else. You need to be looked at first.

(20:55) There are some additional considerations if you're a diabetic because it can possibly lower your blood sugar too with your diabetic medication.

(21:06) Glucosamine is generally safe but should still be avoided until day 100 post-transplant. So, glucosamine is probably one of the ones that's been around the longest and has a lot of reports out on there. Glucosamine supports your cartilage. So, it's used for all those parts of your body around joints such as knees, shoulders, jaws, that's where glucosamine comes in and helps to reduce that inflammation. It is considered an anti-inflammatory. It helps with the swelling.

(21:32) The data for glucosamine being effective is really all over the place. So as many studies that there are that say that it's effective, there are plenty of studies that say that it's not effective, the good part here being that at least it's generally safe to take. We still tend to avoid it in the immediate transplant phase, which is before around day 100 because it can rarely affect your liver, but in general, it's a fairly safe supplement to take. However, if you do have low platelets, you do want to use it with caution and there are some reports of patients with glaucoma that it increases your intraocular pressure, so you probably don't want to take glucosamine for your joint issues if you have glaucoma.

(22:22) Garlic supplements can affect bleeding rate and reduce the effectiveness of cyclosporine. It’s not recommended before or after transplant. The next supplement is garlic. And once again, garlic when used in cooking, like turmeric, is generally fine to take, and not a deep consideration, but when you're looking at taking garlic supplements, you want to be a little bit more careful. So, people take garlic mainly to prevent or treat heart disease. It's also thought to stimulate the immune system and have some antioxidant-like effects.

(22:50) The studies surrounding cancer and garlic have been mostly surveys and they're not overly scientific. I feel like if you survey enough people, you can find correlation with almost anything, and that's about what it looks like for the data behind garlic.

(23:08) Sometimes, garlic can affect your bleeding rate. It also affects some of your medications like cyclosporine, which is commonly used medication after transplant. It does interact with cyclosporine and makes it less effective, so it's definitely a consideration. You certainly wouldn't want to get worse graft-versus- host disease because you decided to take a garlic supplement.

(23:37) As I said, it can increase your risk for bleeding too. So if your platelets are low or you're on any other blood thinners or anticoagulants, you want to avoid garlic. If you're going into surgery, you also need to hold it for at least two weeks. Garlic can affect medications that are metabolized by your liver also, so in general, I don't suggest that you take garlic supplements before or after transplant.

(24:05) Milk thistle is not recommended while on any other medications. The next one is milk thistle. So, I get asked about milk thistle a lot. And in general, what I know about milk thistle is it's for your liver. It's supposed to be fantastic for your liver, is what everybody tells me. The problem is that anytime you have something that supports your liver, and we all know how important the liver is for everything, there's also a high chance that that is going to affect every other medication that goes through your liver. So, it's been shown to affect the immunosuppressive agent sirolimus and some of the other medications that you sometimes use for nausea like haloperidol. And it can increase the concentration of some of the antifungal agents such as fluconazole, voriconazole, posaconazole. So milk thistle is not a supplement that I would recommend taking if you are taking any other medications. And because it does affect your liver so much, it can cause liver side effects too like cirrhosis, hepatitis, even though it's supposed to support it, it has been linked to it also.

(25:20) Black cobash is not recommended due to liver toxicity. Next up is black cohosh. So, black cohosh is used mainly by women for menopausal symptoms. Specifically, people like to use it for hot flashes. It also can help fight osteoporosis. It's been studied a lot in the breast cancer world, not so much in the stem cell transplant world. The safety and efficacy has not been thoroughly studied, and there have been enough cases of liver toxicity associated with black cohosh in the entire population, not specific for stem cell transplant, but in the entire population, they have looked at it and there have been enough cases of liver toxicity that a warning is now on every bottle that has black cohosh in it. So even if it's in a combination product, there is a warning for liver toxicity. And so as I've been saying, you really got to watch out for that liver and anything that goes through it.

(26:13) We do know that when black cohosh is taken with other prescription medications such as certain chemotherapy drugs or immunosuppressants, it can alter their metabolism. So, it is also not one that we recommend taking. If it is something that you really want to try, it needs to be a discussion with your healthcare provider. And then, you also have to watch out for your risk of breast cancer because then it's a definite risk versus benefit area too.

(26:43) St. John’s Wort has an extensive list of drug interactions and can reduce the effectiveness of other important medications. St. John's Wort: this may be the most studied of any of the herbals that I have talked about. St. John's Wort has historically been used for depression. It's been used for many, many, many years. And there are several studies that actually do support its efficacy. However, St. John's Wort is a strong inducer of your liver enzymes. An inducer means that it makes the enzyme work much better.

(27:08) So drugs that require the enzyme and think that it's working at a normal level will then get... when you take the St. John's Wort, the enzymes that break everything down work much, much better and you may never actually get to therapeutic levels because we base things on a normal enzyme levels. And so, because you're breaking down so much more when you're on the St. John's Wort, we have a hard time getting medications to their therapeutic levels. So, it can affect both cyclosporine and tacrolimus, and then it also affects some blood pressure medications. The list of drug interactions with St. John's Wort is actually very extensive. It's been very well studied and is actually listed in a lot of your prescription medication package inserts because it does tend to cause so many drug interactions. So, my advice on St. John's Wort is that we probably have prescription medications that are safer to take with your current medication. But if you happen to not be on any medications, then it would be safe enough to try.

(28:21) There is some caution with it, too, with it causing some sun sensitivity. You just want to watch out if you start to sunburn a little bit easier.

(28:32) Saw palmetto has unproven benefits, many drug interactions, and increased bleeding risks. Saw palmetto: this one is used by men. It's used to lessen the symptoms of BPH or benign prostatic hypertrophy. It is thought to have both anti-inflammatory and anti-androgenic properties. The efficacy has not been proven. In one trial comparing it to a placebo, it did not show any benefit. There are also a lot of studied drug interactions with saw palmetto. They know that it does get metabolized in your liver and can affect your liver enzymes, but there aren't a lot of data that it actually affects anything at the time.

(29:19) One thing to watch with saw palmetto is that it can increase your risk of bleeding and it can have some additive affects to coagulants. So, you want to make sure you have a good platelet count at least before starting it. But in general, it's fairly safe to use.

(29:33) Valerian can help with sleep but it prolongs drowsiness and should be avoided in transplant patients for several reasons.  And the last individual one I'm going to talk about is valerian. I think sleep is probably one of the biggest issues that I get asked about for stem cell transplant patients, and really, the entire population as a whole seems to have sleeping issues.

(29:54) So, valerian is an herbal supplement that helps with sleep. It may also help with some anxiety and some muscle spasms, but there are a lot of interactions with valerian too, mainly due to the additive CNS effect, or your brain effects. So, it can make you drowsy for longer. During the day, the effects don't wear off. While you're sleeping at night, it can prolong your drowsiness after you wake up in the morning. And sometimes, can have additive confusion.

(30:25) In addition, there are more negating side effects when it's combined with other agents too. So, if you're on anything like Ativan or Lorazepam or Haldol, haloperidol, it can make you more sleepy than you would normally be taking either of those products alone.

(30:45) There have also been cases of pancreatic and liver toxicity from taking valerian. They actually recommend you stop it at least a week before surgery since it can interfere with anesthesia too and make it harder to come out of that anesthesia.

(31:01) It is metabolized by your liver. We don't know a lot about the interactions with it other than the additive CNS effect, but we usually try to avoid it in the stem cell transplant patient.

(31:12) Melatonin may help with sleep. Melatonin is another herbal product that is considered much more safe as a sleep additive if you need something for sleep.

(31:25) Many other herbals affect the liver and should be avoided by transplant recipients.. This is a list of other herbals that we tend to avoid in stem cell transplant patients. Most of these again have some effect on your liver, like the Chaparral or the Comfrey, Kava Kava. Some may affect your immunosuppression agents and other have known adverse effects on the stem cell transplant patient. So, you want to be able to look for these ingredients on your product labels and avoid any supplements that contain additional herbal products.

(32:01) Check labels for quality supplements and USP or USP-NF endorsements. So as we're looking for things, these are things to look for when you're considering starting an herbal supplement. To look for quality herbal supplements, you want to look for either USP or USP-NF on the label. USP is an independent organization that's dedicated to quality control. So, it actually reviews them all for quality and their strength, quality and purity. They don't speak to efficacy, but if it has a USP or a USP-NF on the label, you can at least be sure that what it says on the label is what's in the bottle.

(32:39) The NF on it refers to the National Formulary. This includes over 5000 quality standards for both the active ingredients and the excipients. And so, it's a great reference also to use as you're looking at the labels.

(32:54) You want to make sure that only the part of the plant that is useful is in the product, since I did say different parts of the plant can have different effects. This may not always be apparent on the label, but it's always nice if manufacturer includes it. Hopefully, also on the bottle, there will be a way to contact the company. You want to be able to contact the company in case you do have any adverse effects or if you have questions about the supplement. Sometimes, you may have questions. I get asked a lot like, "I left my supplement in the car. Is it still going to be good? It got too hot." I'm in Arizona, so we deal with the heat more, but other places may have to deal with the cold more. And I don't know other than going to the manufacturer for how they have actually tested the product for whether it's stable or not stable or if there's any danger between taking a product that you may not know. So, having the company information to contact is great to have.

(33:54) Add supplements and medications one at a time to monitor their effects. Also to take into consideration when you're thinking of adding an herbal supplement into your medical plan is to add things one at a time and make sure that you tolerate them. And this, we try to do with medications too. You want to make sure that what you're adding is going to give you the expected result and that it's not going to cause any unwanted side effects. If you add five products at one time and you're very nauseous or something like that, you don't know exactly which one is causing that. So, take it slow and do one at a time and try to avoid the mixtures in the supplements and get the single product supplements and then add them one at a time so you can make sure that you're going to tolerate them and see if it gets the effect that you're looking for.

(34:38) And of course, you want to follow the dosage limits that are suggested on the label. You don't want to increase over what the manufacturer is recommending.

(34:48) Avoid megadosing; it can cause problems. So, things to avoid when you're considering adding herbal supplements into your medical plan: megadosing. Megadosing is when you're mostly... I think of it in terms of vitamins and minerals, things that give you a percent daily recommended value. So, you see this routinely in multivitamin supplements or Vitamin C, Vitamin D. Anytime that you're looking at something that's hundreds and thousands of times the daily recommended value, that's considered megadosing. More is not always better. And most of the time, you end up excreting all the extra out anyway. And if you don't excrete it, then it can also build up, which that can cause problems also.

(35:38) Additional cautions to keep in mind. You always want to avoid the thinking that natural equals safe. Hopefully throughout the discussion today, you realize that even natural products have unwanted side effects that can affect other things in your medical plan.

(35:50) Other things to watch out for are any product that claims to work as good as a prescription medication because by law, they're not allowed to say that. Anything that's advertised through mass emails, if they're trying to push the supplement on you that hard, it's usually not a reputable source.

(36:12) And then, in general, the products for weight loss, body-building and enhanced sexual performance all tend to have a broad proprietary mixture that they don't want to tell you exactly what's in it and those can be more dangerous to take.

(36:29) Stem cell transplant patients should avoid supplements for the first 100 days, use caution thereafter, and consult with their medical team. My advice for the stem cell transplant patients, specifically, is avoid supplements when you're on any active chemotherapy and for at least the first hundred days after your auto or allo transplant. You want to make sure how everything's going in that initial phase after your transplant and you don't want to add anything into the mix.

(36:50) You want to use caution after day 100, and you want to discuss these things with your medical team first. There's usually their pharmacist or physician, an NP, somebody that's able to scan and see if there's going to be any interactions with the medications that you're already taking.

(37:06) You want to make sure to look for good manufacturers and always include any supplements when you're discussing your health care with your medical providers too. Very helpful to have a list of supplements when patients come in so that we can make sure everything's safe. And of course, if there's anything going on that's different with your liver or your kidneys or anything like that, it's nice to be able to review the entire list of the herbal supplements before coming.

(37:34) There are helpful web resources on this topic. And then, this is a slide that has some places to go for additional information on herbal supplements. The top one is the National Institute of Health and it has some great resources along with some detailed fact sheets. And there's an also an app through the National Institute of Health that you can download onto your smart phone or tablet and is very useful to keep up with your supplements.

(38:03) The middle one there is the National Center of Complementary and Integrative Health, and this is a division of the NIH, and it has a section when you go to that website that's called Herbs At A Glace and it lists all the herbal products alphabetically and you get some really get some really great, concise information and you can actually break down some of the studies or what they know about it for efficacy too.

(38:28) And then, the last one is the Memorial Sloan Kettering Cancer Center website that also has a great resource called About Herbs. And you can search it for the individual herbal product and it breaks it down to the top part of patient information and then the second half is healthcare provider information. I've used that a lot also in giving people advice and what to watch out for when taking the herbal products.

(38:58) So, that's about it. Thank you for letting me share some information with you guys today. I will take any questions.

Question & Answer Session

(39:12) [Sue Stewart]       Thank you very much. That was really an excellent overview of herbs and supplements. You could probably have gone on for hours with so many out there.

(39:22) [Maggie McCallen]      There are.

(39:23) [Sue Stewart]      There are lots of questions. So, I'm going to try to make sure everybody gets at least one question answered. And we'll start with the first one: "Is Biotin okay to take a few years after transplant? Does it really help with hair and nails, and if so, at what dose?" And then the second question this person asked along the same line is, "Do you have any idea why an endocrinologist would advise against taking this for mild hypothyroidism?"

(40:00) [Maggie McCallen]      Is Biotin safe to take a few years after transplant? In general, yes. Biotin doesn't have a lot of drug interactions. So I would say in general, it is safe to take. The second half of that question about the endocrinologist saying not to take it, I can't speak to that. I'm not sure why they would say that. I can't think of any thyroid interactions off the top of my head, but I'm not positive on that one.

(40:35) [Sue Stewart]      So, probably a good question to ask the endocrinologist.

(40:41) [Maggie McCallen]      Yes.

(40:41) [Sue Stewart]     Alrighty. The next question is, "Can you explain how an algal source differs from fish oil with regard to Omega-3 supplements? Do they need to be refrigerated?"

(40:55) [Maggie McCallen]      A lot of the Omega-3 do need to be refrigerated and the nuts, they do tend to... it depends on where you live and the environment that you keep them in. Most of the oil and nut seeds, things like that, they do tend spoil for too long at room temperature. So, they do suggest keeping a lot of them in the refrigerator. And most of your herbal products can be kept in the refrigerator without any adverse effects to it anyway. What was the first half of that question?

(41:39) [Sue Stewart]      They were asking about algal products? DHA source for Nalgene?

(41:46) [Maggie McCallen]      Oh. I'm sorry. I don't know about that one specifically, but I'm happy to look into it and get back to you.

(41:53) [Sue Stewart]      All right. The next question is about the ever popular CBD. "What do you think about taking the CBD product to sleep with or without THC?"

(42:07) [Maggie McCallen]      Yeah. So, I specifically tried to avoid talking about CBD and THC because I did know there was another discussion on that at this presentation too. So, CBD in general is thought to have some beneficial properties. A lot of it would depend on if you're taking other medications.

If you're taking any immunosuppression like tacrolimus or sirolimus or cyclosporine, you would want to be more cautious. My advice is usually, if you're taking it on a daily basis, we can adjust things to take that into account. If you're taking it only every once in a while, sometimes, that can be more dangerous in that we don't have consistent levels to necessarily deal with. If you're not taking any other medications, I think that CBD is perfectly safe to take personally. I would look for a CBD product that doesn't necessarily have the THC in it since most of the adverse effects come from the THC component and not the CBD.

(43:30) [Sue Stewart]      "Are there any supplements that can treat eye GVHD?"

(43:38) [Maggie McCallen]      Eye GVHD. I don't know of any supplements off the top of my head and I don't think that there have been supplements tried for that. I know there's a lot of... we have an ophthalmologist here that does autologous tears and stuff like that that they can make from your serum and use those. I don't know of any supplements specifically for eye GVHD.

(44:09) [Sue Stewart]      All right. Good information. The next person has a question about lion's mane mushroom powder. She says it's helped her dramatically with mental clarity. And she also believes that some of the legal mushrooms have been used in NIH cancer studies, and she wants to know if you know anything about those and if you have an opinion about that.

(44:30) [Maggie McCallen]      I don't know anything specifically about that mushroom. I do know that there are a lot of mushrooms that are being studied and that can have a lot of great effects on your immune system. So post-transplant, it's probably safe enough to take. But there are a lot of mushrooms that can affect the liver specifically, and so it's something to watch out for. And in general, if you're taking it and you feel like it's working and everything is going fine, then I think it's perfectly safe to take. I love it that herbal products are becoming so mainstream and that I do think we are studying them a lot more, but I don't know anything specifically about that.

(45:16) [Sue Stewart]      All right. The next question is about Vitamin D. "Is it harmful to take too much of Vitamin D?"

(45:27) [Maggie McCallen]       So, Vitamin D can build up into fat cells. It's one of those vitamins that is not water soluble, and so it can build up. But Vitamin D is also something that you can check levels on. And so if you're worried about taking too much Vitamin D, you can always get a level drawn and if it's excessive, then stop taking so much. But in general, I think the vast majority of the population is probably Vitamin D deficient to some extent, so a little bit of Vitamin D is not usually bad. But you can overdose and have too much Vitamin D. So, it's important not to take over whatever your provider is recommending at the time. Sometimes, you do a daily thousand micrograms a day, sometimes you do 50000 units a week. Most of those, your doctor or nurse practitioner, PA, can help you with get a level and make sure that you're on the right supplement there.

(46:36): [Sue Stewart]      All right. Our next question is about essiac tea: burdock root, slippery elm, sheep sorrel, turkey rhubarb root. "Is this proven safe and effective?"

(46:51) [Maggie McCallen]      I would definitely have to look into that. A few of those I think... you said turkey something root. I do remember having some adverse effects associated with it. I don't know that supplement specifically. I would have to look into that to say if it's safe. I think some of the time with supplements, for effectiveness, you're not going to get the widespread studies that prove that it's effective, but if it's something that's safe to take and you try taking it and you feel like it's effective, then that's probably the best gauge to go by.

(47:32) [Sue Stewart]      All right. The next question is about garlic. "How effective is raw garlic to lower high blood pressure?"

(47:40) [Maggie McCallen]      Yeah. There's a lot of studies that are looking into that. How effective is it? I don't normally recommend it as a single agent. It can be an additive agent with some of the other blood pressure medications, but it on its own doesn't tend to lower it enough to get you within the desired range.

(48:08) [Sue Stewart]      All right. The next person has a question about Omega-3. He said he's heard some negative things about fish oil so he's taking extra virgin olive oil, and he wants to know if that's a good substitute.

(48:24) [Maggie McCallen]      They don't really have the same properties associated with it. You don't get the Omega-3s, the fatty acids, that are not present to the same extent in olive oil, so it's not necessarily a good supplement or a good exchange between the Omega-3 fatty acids and olive oil. You're not getting the same benefit from it. You get other benefits, but it's not necessarily a one-to-one substitute between Omega-3s and olive oil.

(49:01) [Sue Stewart]       Good to know. Thank you. This gentleman is on Revlimid maintenance therapy, and he wants to know what you think about taking Zinc, Potassium, B12, fish oil or Vitamin D while he's on Revlimid.

(49:18) [Maggie McCallen]      Zinc, Potassium, Vitamin D...

(49:27) [Sue Stewart]      Fish oil and B12.

(49:29) [Maggie McCallen]  ... Fish oil and B12. Okay. So, all of those, the fish oil, if you've been on fish oil for a while, you are probably okay with continuing it. With Revlimid maintenance, the rest of them, the Zinc, Potassium, Vitamin D, B12, those are all perfectly fine to take with the Revlimid.

(49:52) [Sue Stewart]      Okay. Next question's interesting: "How can I tell if a supplement is manufactured in China versus the US?"

(50:02) [Maggie McCallen]     Yeah. So, I think that that's a great question and I think when you're just in the store and looking at the bottle, most places that manufacture in the US will state on it that they manufacture in the US. I feel like it's foreign countries that sometimes try to hide where it's being manufactured. If you are unsure, I always just would look it up on the internet and it will usually bring you to the website and there will be somewhere that it can tell you. If you can't find where something is manufactured, I would not buy that supplement because I would question why they're trying to hide where it is manufactured.

(50:45) [Sue Stewart]      Okay. Probably good advice to follow. Ginger: this woman would like to know if it's similar to turmeric and is it safe to use or recommended to use for inflammation?

(50:59) [Maggie McCallen]      So, ginger does have a lot of anti-inflammatory properties. It's not as potent I would say as turmeric or curcumin. Turmeric tends to be a lot more potent on those liver enzymes and stuff as opposed to just the anti-inflammatory. So, ginger is probably a little bit safer to take. But it does have some bleeding risk associated with it also. I don't know what other medications that you may be on. If you're not really taking any other prescription medications, then ginger is probably safe to take.

(51:44) [Sue Stewart]       All right. This is a question about Vitamin B1: thiamin. The woman says, "I recently could not find thiamin B1 vitamin, so I purchased B complex. Is that overdosing?"

(51:59) [Maggie McCallen]      No. That should be fine. And all the B vitamins are water soluble vitamins, so if you are getting over what your body needs, your body will just excrete those out. And so anything that's a B complex or a combination of B vitamins are safe to take.

(52:19) [Sue Stewart]      All right. This one is asking a question about something I'm not familiar with, so I hope you are. She wants to know what your thoughts are on Schiff Move Free Joint Health Supplement?

(52:33) [Maggie McCallen]      I think that is probably a glucosamine chondroitin supplement. I think that's a fairly popular brand with glucosamine and chondroitin, but again, I might be guessing at that there.

(52:47) [Sue Stewart]      That's all right.

(52:52) [Maggie McCallen]      So glucosamine, like I said, doesn't have a lot of drug interactions, so it's fairly safe as long as you have a good platelet level. Glucosamine in combination with chondroitin is a perfectly fine combination.

(53:05) [Sue Stewart]      All right. We have a question from someone who's got difficulty with migraines. She says she's been diagnosed with migraines after an allo transplant and her transplant provider provided her with magnesium supplements. However, her neurologist recommends magnesium plus taurate as a preferred form for migraines. And the only place she could find it was a health food store, not in a pharmacy. It does not have a USP or NF on the label. Do you have any recommendations where she could access a safe form of this magnesium?

(53:42) [Maggie McCallen]      I'm sorry. What form of magnesium was it?

(53:46) [Sue Stewart]      The neurologist recommends magnesium plus T-A-U-R-A-T-E.

(53:54) [Maggie McCallen]      Okay. I mean, I don't know a reputable place off the top of my head. I can certainly look into that for you. I do know magnesium is often recommended to help with migraines. The neurologist knows better than I do. The specifics all work differently. If it's something that you have a hard time finding, you can try different magnesium supplements and see if they help with migraines, but if you find that only the taurate is the one that works for you, then I would have to look into where to find that. I'm not familiar with finding that. But typically if the neurologist is suggesting it, they usually will tell you where to find it.

(54:40) And just because it doesn't have a USP or USP-NF on the label doesn't mean it's not a reputable source. It's just one additional level of safety that you can look for when looking at supplements.

(54:55) [Sue Stewart]      Okay. We've got a couple questions about CoQ10. They want to know if that's safe or effective.

(55:05) [Maggie McCallen]      Yeah. I get asked about CoQ10 a lot too. There are a lot of interactions with CoQ10, so it's one that I try to avoid within the immediate transplant phase and wait until everything's kind of stabled out. If you're on stable levels of medications and everything, then it might be okay to try the CoQ10 supplement. The studies out there are really all over the place with that too. I really think that they're doing a lot better controlled studies with it and that we'll get some of those results soon, but as of right now, I can't really speak to the efficacy of it. But I'm excited to get more info.

(55:57) [Sue Stewart]      Great. Great. More info is what we need. All right. This person wants to know about herbal green tea. Is it safe after transplant, if you're currently on cancer treatment, to drink that?

(56:11) [Maggie McCallen]      Yeah. So I usually tell my patients, if you have a glass of green tea a day, you're probably okay. You just don't want to overdo it. And if you're currently taking medications like immunosuppression, a lot of things, we can draw your levels. And if you take the same amount, green tea's one of those, if you take it as a supplement like in a capsule form, it has a lot of interactions. But if you're just drinking it and you tend to drink the same amount on a daily basis and you don't overdo it with six glasses a day but kind of restrict it to one glass a day, you're usually fine.

(56:53) [Sue Stewart]      All right. The next question is about calcium, magnesium, and zinc. What type is best to take: gluconate, citrate? And what is the maximum dose of zinc?

(57:08) [Maggie McCallen]      Well, zinc is one of those hard ones because if you do take too much zinc, there have been some adverse effects and it can definitely affect your sense of smell, your sense of taste. I don't know the recommended dose off of the top of my head. I can get back on that. But it is one that you definitely don't want to overdo it on.

(57:34) Then calcium, as far as the salt form, the citrate does tend to absorb more readily than some of the other salt forms. But a lot of it's based on what you can tolerate too. Any calcium supplement should get you to a decent calcium level if taken enough. It's just a matter of what you can tolerate taking. And I feel like it's very personal in that some people love calcium carbonate, which you can get from Tums and they'll just do Tums all day long and that will supplement your calcium too. So, I would say that calcium citrate has great absorption, but a lot of it's what you want to take and what you can tolerate.

(58:27) [Sue Stewart]      All right. And unfortunately, we are near the end of this session, so I'll take one last question. The question is, "What is a good supplement for severe leg cramps?"

(58:40) [Maggie McCallen]      So, the safest, I mean, I'm not sure what you've tried in the past. I know a lot of times, magnesium can help with severe leg cramps or can at least lessen the severity of the leg cramps. And so a lot of times, magnesium will help with that. I know historically, quinine has been used, but that has some bad interactions too. So, it's not one that I recommend. I would have to look into your medication list and probably have a discussion for what's been tried or not tried, but I would say the safest would probably be a magnesium supplement there.

(59:26) [Sue Stewart]     Closing. Well, thank you. This has been an informative discussion. I appreciate all of your comments Maggie as well as the questions that came from the audience, lots of good questions. Lots remaining, unfortunately that we couldn't get to, but I think we've got a good basis of understanding of how to evaluate supplements and which ones are safe to take and which are not.