Herbal Remedies and Supplements: Are They Safe? Do They Help?

Presenter: Queenet Ibekweh Pharm.D, BCPS, BCOP, Miami Cancer Institute/Baptist Health South Florida

This is a video of the workshop presented at the 2019 Celebrating a Second Chance at Life Survivorship Symposium.

45-minute presentation, followed by 15-minute Q&A

Summary:

Herbs and supplements are a $4.2 billion business in the U.S. that is not well-regulated. Many popular herbs and supplements can be problematic for transplant recipients, especially those who are immunosuppressive drugs.

Highlights of Talk:

• Contamination can occur in the manufacturing of herbs and supplements, which can be dangerous for transplant recipients

• Some herbs and supplements interact badly with prescribed drugs transplant patients are taking

• It’s important to tell your health care provider about all herbs and supplements you take, so that you can remain safe and the prescribed drugs can be effective.

Key Points:

13:22  If the label on an herbal product or supplement says the product has not been evaluated by the FDA, it means that the claims made about the product’s usefulness have not been verified.

14:31  A major concern with herbs and supplements is whether they interact badly with other medications you are taking.

17:57  Blue-green algae, used by some to stimulate appetite, may be contaminated in the manufacturing process.

21:16  Herbs and supplements heavily metabolized by the liver, like echinacea, can interact badly with medications prescribed for transplant recipients

22:40  Ginger can help with nausea and vomiting, but can also cause increased bleeding, particularly if a patient is on blood thinners

26:58  Kombucha is very popular but, particularly when bought online, has a risk of bacterial or fungal contamination

34:28  Studies have shown turmeric is effective in reducing inflammation, but it can also reduce the effectiveness of immunosuppressive drugs.

36:25  Valerian is popular for managing sleep problems, but may interact badly with other drugs prescribed for transplant recipients

43:24  Memorial Sloan Kettering Cancer Center has an excellent database with information about herbs and supplements you may be considering.

Transcript of Presentation

00:00  Introduction. I'm really glad to be here, it's very inspiring listening to the stories, looking at the happy faces. It's really an honor to be here with you and to share this information.

So, we will be going over herbal remedies and supplements, are they safe? Do they help?

I'm the BMT clinical pharmacy coordinator at my hospital. It's a pretty brand-new facility in Miami. I started when we actually started our transplant program. Unlike other cancer centers, when we started our autologous stem cell transplant program, we started in the outpatient setting and then moved over to the inpatient side.

So,our first allo transplant patient or transplant from using donor cells will be in July of this year. But from my previous experience here in the states and in Saudi Arabia, I've always loved blood and marrow transplant. It's been a passion of mine, and I'm hoping that I can share some valuable information with you all today and hopefully get some questions at the end of the presentation.

I promise I have no relevant financial relationships to disclose in the US and Saudi Arabia included. And I have no actual or potential conflict of interest in relation to this program.

01:19  Overview of presentation. So, my hope is that by the end of this lecture, or sessions that we will, first of all, review certain patient cases that I've encountered in my practice. 

Also, I would like to describe herbal remedies and supplements to which transplant recipients may potentially be exposed to. 

Of course, I hope that our patients, caregivers, and other healthcare professionals who may be in attendance will be able to recognize certain side effects associated with the use of common herbal supplements. And I will revisit the patient cases and discuss recommendations.

01:59  Is CBD oil safe for transplant patients?. So, our first patient is Mr. Andrews. Mr. Andrews is a 30-year-old patient diagnosed in 2012 with Hodgkin Lymphoma who received stem cell transplant with own cells in October of 2018. So, when he presented to the outpatient clinic and requested to speak with a pharmacist his question was: "can I continue using CBD oil? I use it now, it works great for nausea, pain, and anxiety."

So, upon further review of his home medications, the patient is also receiving prochlorperazine, also known as compazine, every six hours as needed for nausea and vomiting, acyclovir every 12 hours for prevention of viral infections and CBD oil in e-cigarettes and baked goods as needed for anxiety, nausea, and pain.

Now, I really should put that in bold; because quite frankly, we had to pry that information out of the patient because we weren't quite sure if it was really e-cigarettes or it was something else that was being inhaled at home. So that was questionable, but that was what he shared.

Now, of course, pharmacist's patient confidentiality: we always have to make sure that our patients feel very comfortable with us. So, there is never any judgment in these sessions. I am more concerned that at the end of the transplant, and moving forward, that the patients remain in good health. We never judge a what our patients share with us; but it's very important that this information be disclosed during our counseling sessions.

03:40  It’s important to check purity of CBD oil. So as a pharmacist, I would like the entire audience to take a walk with me down memory lane and imagine you're the pharmacist. So you have a patient that's sitting right in front of you, he's disclosed that he's using CBD oil. So as a pharmacist, there are certain questions you have to ask. You ask the patients, and of course you ask yourself, because you need to make sure that you have all the information that you need, anytime we run into a scenario like this where a patient is consuming CBD oil, we always ask our patients to be completely honest with us and tell us what exactly they're taking at home; and where exactly is this being purchased? Is it being purchased from an office, down the street, or is it being purchased online? Because this actually does make a difference because we would like to determine what really is the purity and how can we vouch that these patients are not at risk for potential contamination of these products, particularly with products that are being sold online. And we'll go over that in more detail in the coming slides.

04:46  Important to consider whether CBD oil interacts poorly with other drugs a patient is taking. In addition to determining safety and efficacy of these herbal supplements, we also want to make sure that there are no contraindications or drug-drug interactions that can happen with prescription medications and medications that are purchased online. So as a pharmacist, it's our responsibility to make sure that we have all the information we need to be able to discern if there is a potential interaction between prescription medications, particularly in patients who have received a transplant from donors. Because in that scenario, there is the concern that for patients who are on immunosuppression, there can be these severe drug interactions with herbal medications.

So honestly, this slide, I don't want you to think I'm promoting either hemp or cannabis oil. Full disclosure, these two products, you will see, it's up and coming now, it's the new kid on the block, the use of CBD oil. And it is very concerning, and I'll go over major facts, but just to give you an idea, when you hear CBD being discussed, CBD oil can be derived from different cannabis variety plants. People can extract CBD oil from either the hemp plant or from the marijuana plant. There is a difference between what is actually being sold online and in different stores that have popped up across the US. So, what I would like to draw your attention to on this slide is, pay attention to first of all, the product. Are we looking at CBD oil that has been extracted from the hemp plant or from the marijuana plant?

06:36  Labeling of CBD oil products about what it can do is often misleading. Also, as a pharmacist, we also want to pay attention to what label, what indication is being advertised for the use of these products; because a major concern is that a lot of companies are coming out with these CBD oil products and they are claiming everything under the sun, including treatment of HIV and AIDS, treatment of cancer, anxiety, nausea. And quite frankly, there is no scientific base to make these claims. So,this is a problem. And unfortunately, not a lot of people are familiar with how these products are regulated. So,we'll go over that in more detail in the coming slides.

07:15  The method used to extract CBD oil from plants may affect safety. I'd like to draw your attention to also the extraction technique; because when these products are used to extract CBD, which is cannabidiol, there is the concern that the extraction technique can potentially be toxic. So, you can see the use of GMOs or trans fats or hydrocarbons being used to extract these oils. Now, unfortunately with any medication in the market, we really can't tell what the long-term side effects are until these products have been used for years. And we're hoping that patients who do experience any side effects will be able to report this through the right pathways. So, it's very important that we pay attention to these main facts, extraction, ingredients, additives, the product that these oils are actually being extracted from and the potential for contamination. So, that's the take home message from this slide. There is no good guy or bad guy, it's just knowing what you're getting. That is the primary focus.

So, we'll get back to the use of CBD oil and extraction and major concerns in the healthcare field, but we can move on to patient case number two, who is Mr. Edward.

08:32  Can over-the-counter medications be taken while on chemotherapy? Mr. Edward is a 46-year-old man diagnosed in 2018 with Hodgkin's Lymphoma, currently receiving cycle two of the chemotherapy regimen ABVD at the outpatient cancer center. And his main reason for the visit was to ask the pharmacist, "I have a few medications I purchased online and over the counter. I need to know if they can be taken with chemo." So, this was his concern, his primary concern during his visit. I always have to look at the whole medications our patient is also getting ondansetron, also known as Zofran, every eight hours as needed for nausea and vomiting. And he was on literally a truckload of herbal medications. I've had one patient walk into the clinic with a little carry-on suitcase- I'm not making this up- every single medication and there was all herbal, purchased either from the local pharmacies or online, which is the new pathway for dissemination of these products.

 For your reading pleasure, you can see the products that he had purchased online and he needed to know, would this be a problem if I take these medications with the chemotherapy? And being that he's a 46-year-old man with Hodgkin Lymphoma, good performance status, definitely down the line there is the potential to proceed with the transplant with his own cells. So, we always have to look at the big picture and see how this could be a potential problem as if he does approach the transplant phase. So, as the pharmacist, when I see herbal medications in the clinic, my spider senses go off. And my major concern is: when I have these patients on herbal medications, again, full disclosure, I ask, is there any medication that a friend has given you or a relative or you've purchased online or you've picked up at the local pharmacy? Tell me, what are you on?

So, patients are generally very comfortable with their pharmacist; so, I get a lot of the juicy details that they don't share with the physicians. And of course, they feel very comfortable, which honestly, is the goal because we are not there to judge. We're there to make sure that there are no adverse effects that can happen with the use of medications. Because the last thing we need is for a patient to go through transplant, get into remission, and then suffer from acute liver failure due to an herbal medication. That is a terrible outcome. And so, I always have to ask, are there herbal medications you're on? And then of course, assess the chemotherapy regimen that our patients are on to make sure that there are no drug-drug interactions that can 

11:33  It's important to read the label on herbs and supplements to determine the active ingredients. Moving on, when I look closely at each of the products he came in with, I've extracted the active ingredients or the active herbal supplements that these products contain. And number one, you see echinacea, which is a very common one. I think there's no one who probably hasn't heard of this or you may even know someone who's on it right now. But that was one of the ingredients in one of the products that the patient came in with. So, garlic powder, carrot powder, glucosamine, and turmeric. Very common ones.

12:10  Sales of herbs and supplements is a $4.2 billion business in the U.S. So, on the right, which you see over here, these are other common herbal supplements that are being sold online. You may know someone who has vouched for its efficacy. Products like blue-green algae, ginger, hawthorn, milk thistle, saw palmetto, Valerian: these are very common herbal supplements that you will hear. Or if you haven't heard about it, I'm pretty sure that this will be one that you will not miss especially now that the market has grown exponentially. I mean, this is a massive gain for a lot of these companies. I mean, look at a company in 2000 that showed a total estimated US retail sale of herbal supplements of $4.2 billion. We are purchasing these medications. So, people are suffering from adverse effects, whereas other people are making a lot of money from this. So, this is why we have to be very aware of what we're actually ingesting.

13:22  If label says the product has not been evaluated by the FDA, it means the claims about its ability to help or cure have not been verified. Because the truth is, and I'll go over this in more detail, that a lot of these products that you see in the local pharmacies and online, they must have this statement written on it: which is "these statements have not been evaluated by the Food and Drug Administration.

This product is not intended to diagnose, treat, cure, or prevent disease."

If an herb or supplement has not been approved by the FDA, the claims made about its ability to helped have not been verified. This is a necessity on any herbal product that is sold because there is no herbal supplements that has gone through the rigorous process of FDA validation.

So, they cannot claim that these products can treat cancer or can treat HIV AIDS. A lot of these statements are all bogus. So, we have to really pay attention to what we're purchasing from our local pharmacy. So, you see in 2016, total estimated sales went up to $7.5 billion. So, someone's making good money from this process. But please pay attention to this, and I'll go over this in more detail.

14:31  Major concern with herbs and supplements is whether they interact badly with other medications you are taking. So, in general, when I think of herbal supplements and remedies, and I've been going over this information since I was a student, when I was a resident, and now of course as a clinician, is that are major things that need to pop out, major red flags that patients, caregivers, healthcare professionals needs to be aware of. Number one is the drug-drug interactions. I mean, this is a major concern because, remember, a lot of our patients are on immunosuppression. A lot of our patients are on anti-fungals, antibacterials that are predominantly metabolized through the liver or cleared through the liver or the kidney. So, we need to make sure that no additional herbal supplement can interact with these medications that actually serve a guaranteed purpose. And that of course can lead to an increased side effect profile of your immunosuppression drugs, cyclosporine, tacrolimus, we have to make sure the levels are accurate. So, you don't want any potential interaction. So, this is very important.

15:38  Contamination of herb and supplements in the manufacturing process is not monitored by the FDA. Contamination of preparations: we'll go over this in the following slides; but there are a lot of reports of lead poisoning that have been found in some herbal supplements. Because when the FDA, the Food and Drug Administration, when they do not monitor how these products are manufactured or dispensed, then you really can't vouch for how clean the preparation technique is. So, then we're running into issues where patients have lead poisoning and can die from lead poisoning versus having survived ALL. So, this is a huge problem that we really need to pay attention to.

16:22  Monitoring herbs and supplements by the FDA for toxic side effects is lax. Toxic side effects of these medications, which can range from nausea, vomiting to end organ damage, kidney failure, liver failure. We need to pay attention to this. And of course the lack of regulation by the US Food and Drug Administration, which is, thanks to the Dietary Supplement Health and Education Act that was enacted in 1994, which pretty much says that these companies that produce these herbal supplements, all they really have to do is let the FDA know that "we have proof that this has worked in X, Y, Z settings .So, if we make something similar, we should be fine." That's like a disclaimer. But they do not undergo any of the rigorous clinical trials that your regular prescription medications go through.  The FDA, yes, they watch out for this; but to be honest, the rule of the FDA in monitoring herbal supplementation sale is very reactive. Because they wait and they monitor the market. And based on adverse effects that are reported, then they send warning letters, then they go after the bad guys. But the truth is someone has to be hurt before a difference can be made due to that act from 94. So, these are just things to keep at the back of your mind when you make these purchases.

17:57  If using blue-green algae to stimulate appetite, watch out for potential contamination in the manufacturing process. Herbal drug interactions, I'll go over very common ingredients, very common products that you see in the market. I will start off with a blue-green algae, which of course, the reported use or alleged uses include appetite suppression It's been reported to treat ADHD, HIV AIDS, viral infections and has also been reported to stimulate the immune system.

Now of course, these reported uses have been linked to the activity of causing an increase in the natural source of protein and vitamins in the body and helps prevent high cholesterol in the body. But please pay attention to the herb-drug interaction. So, blue-green algae, yes, in certain countries is ingested as a food product. But keep in mind it really comes down to the preparation of these herbal supplements. When we cannot control how these products are prepared, then there is the potential for contamination. And with this contamination comes drug interactions with immunosuppressant drugs, comes the side effect profiles, which can actually lead to end organ damage, liver failure. So, warning: when you see any product that has blue-green algae, we always have to watch out for potential contamination of the product that can lead to liver damage, kidney damage, or nervous system injury. So, please keep this in mind, [it’s] very well-known especially with its alleged uses in the setting of cancer.

19:42  Safety and effectiveness of Echinacea. Echinacea. So, Echinacea also, there are studies that have shown that Echinacea has certain antiseptic, antibacterial, antiviral properties. So, people tend to think of treatment of the common cold with the use of Echinacea. Also, there are studies that have reported wound healing. But a lot of these studies, they lack the certain level of accuracy, the certain level of safety and efficacy that the FDA looks for in order to designate a drug as a potential curative means.

20:20  Are we denying that a lot of these herbal supplements are effective? No. To be honest, personally speaking, I think a lot of these herbal supplements do have some level of activity. But the problem is how they're being prepared, how they're being sold, how they're being 

There's just not enough data, there's just not enough clinical studies to prove a lot of the alleged uses of these medications. But, yes, Echinacea does have some anti-inflammatory activity. But at the same time, because of the concern of impurity or the concern of contamination, we really cannot say or recommend the use of these medications for the alleged uses, because Echinacea is a particular product, or particular herbal supplement, that is severely metabolized by the liver.

21:16  Herbs and supplements heavily metabolized by the liver, like Echinacea can interact badly with medications transplant patients take. So, when there is the concern for contamination, then you also have to worry about potential drug interactions with other medications that go through the liver. And if I tell you to think of one medication and tell me how it's metabolized, I can guarantee that over 70% of this room will remember or recall a medication that goes through the liver: acetaminophen, Tylenol, goes through the liver. Cyclosporine, tacrolimus, busulfan, thiotepa. A lot of the medications that we see in conditioning and also supportive care in addition to immunosuppression go through the liver.

So, when you have an herbal supplement that is extensively metabolized by the liver with the concern for contamination, then you definitely need to be worried because you do not want anything that could potentially harm you or even compromise your transplant. So, as a warning with the use of echinacea, we always have to watch out, particularly for patients receiving chemotherapy or other medications that are severely metabolized through the liver. And also, there are case reports of potential harm associated with patients who have asthma or require some form of surgical intervention on eye structures.

22:40  Ginger can help with nausea and vomiting, but can also cause increased bleeding, particularly if a patient is on blood thinners. The next agent, very common, well known: ginger. Alleged uses: treatment of appetite, stimulation, treatment of nausea, vomiting, diarrhea. There even case reports of drug withdrawal symptom alleviation with the use of ginger. When we look at the reported activity of ginger, there is some truth to its activity against nausea and vomiting. That is correct. It does have a pretty interesting data that has shown benefit with the prevention and treatment of nausea and vomiting.

But at the same time, there is that interaction, particularly with blood thinners. The data that has been associated with ginger and increased risk of bleeding is pretty well known. And it's a major concern particularly when I do my counseling for pre-transplant and post-transplant. There are case reports that have shown that the use of a certain amount of ginger, usually pretty high doses or amounts, there is data saying that patients are at a higher risk for bleeding. So, when patients are also taking medications, I.e. warfarin, that can increase the risk of bleeding, we want to make sure that they're not taking any herbal supplements that may contain ginger.

But for a lot of these reports or for a lot of these reported uses, we cannot come out, no health care professional can come out, and sell this product or push for the use of this product because there is no FDA backing to any of these reported uses. We do not have the right amount of clinical trials to support the use of these medications. So, this is all based on single center trials or studies that have a small sample population. So, there's really not enough data to extrapolate its use in the real-life setting. And of course, the risk of bleeding, the risk of contamination will always be a problem and what we really need to remember when we seek alternative medicine.

25:04  Glucosamine is widely used to help with arthritis, but also has potential side effects. Glucosamine: very well known for osteoarthritis. When I think of the two Gs, it's usually ginger or glucosamine, very popular. Because a lot of the studies that have looked at the use of glucosamine, they have associated its use with treatment of rheumatoid arthritis or osteoarthritis; and a lot of patients who have issues with their joints tend to rely, or at least give glucosamine the benefit of a doubt. And I've seen a lot of patients come in with bottles purchased from different websites.

Yes, there are studies. But again, it's not sufficient. Okay. These are studies that, quite frankly, could be done better. So, it's really hard to make a recommendation out of these studies. But just to draw your attention to potential side effects associated with the use of glucosamine, stomach upset, there are cases of allergic reactions and potential end organ damage. So, liver failure can happen with the use of these medications because glucosamine is also metabolized in the liver. So, there is that concern that the liver might take a hit.

Now, of course with any medication that goes through the liver, with any herbal supplement that is metabolized or cleared through the liver, we always have to worry about potential drug-drug interactions. We always have to worry about the potential that the liver may become severely inflamed, and that could lead to poor outcomes. A side note similar to ginger: glucosamine has been associated with increased risk of bleeding. So, patients who are on medications, blood thinners, need to be very cautious to avoid any product that may contain glucosamine.

26:58  Komubucha is very popular but, particularly when bought online, has a risk of bacterial or fungal contamination. Now, kombucha: we have this area in Miami, it's called Wynwood. We call it the hip, artsy area. So, it seems like kombucha is sort of like Wynwood because now it's supposed to be hip, it's supposed to be new, it's supposed to be exciting.

Well, not so much. Now, of course I know if you go to Publix, I think it occupies a significant part of the grocery store. There are a lot of products out there, kombucha with different flavors and colorings, which is all great. But my concern here is, pretty much looking at the kombucha teas that are sold online, the ones that quite frankly have not gone through any regulating body. The ones that claim that they have the cure to cancer, cure to HIV AIDS, stomach upset, headache, high blood pressure.

So, when you look at all these indications, you really need to ask, how did they arrive at these conclusions? Because these are pretty big claims. With the lack of supporting data, I mean, to come out and say that one of the uses of kombucha is in the treatment of HIV and AIDS, stomach upset, hemorrhoids, high blood pressure. I mean, this is pretty intense. But I think you might want to wonder if they had the cure to AIDS, I'm pretty sure we'd all know it's in kombucha. That's a lot of money for someone. But just to draw your attention to the lack of data; we still need more studies. It's not clear. They're making very ambiguous claims without the supporting data.

Just to keep this at the back of your mind, reported activity with kombucha. Yes, there are some case reports of antimicrobial properties. There are cases that have shown increased vitamin B level in the body.

29:07  There is a potential for liver damage and allergic reactions with kombucha. But when you look at the potential side effects, this is concerning. There is the potential for liver damage, allergic reactions. Because how kombucha is really made - I'm not talking about the fancy ones in the grocery stores, I'm talking about the ones that they sell in capsules or tea bags online, the erroneous ones - how it's really made is by fermentation of sweetened black tea. And then they add in a mixture of fungus and bacterial cultures for fermentation to happen. So, there is that risk of potential 

And then imagine a patient or someone who has an immune condition with a neutrophil count of less than 500. Chugging down these teas made with a culture, a mixed culture of bacteria and fungus, this is a concern. And because there's that lack of regulation, they can tell you whatever they want to on the packaging. We have to pay attention to this and keep an eye out for the potential adverse events associated with the use of these products.

I'd like to draw your attention to the possibility of contaminated products, particularly with aspergillus and anthrax. There are cases of products that have been contaminated - and of course have led to the death of certain people - so we really have to pay attention to this.

30:44  There are conflicting studies about milk thistle having a protective effect on the liver. Milk Thistle, very well-known particularly in patients who have underlying liver disease, cirrhosis or alcoholic liver disease. There are some case reports that a milk thistle does have some level of liver protection, a liver protective effect. Yes, there is data, but again, not sufficient. Because sometimes a lot of this data is conflicting; two studies might say yea, and then five studies say nay. Then that leaves you in the middle and you're asking, so what do I do? Well, don't do it, don't use it. Because the truth is, without that FDA backing, without that regulation on these products we're taking a gamble, really. It's hit or miss because we don't know what we're going to get.

With milk thistle, it is also a product that is metabolized by the liver. And that is a concern because of the drug interactions that we have and also the potential for liver damage. So, please pay attention to these products. And what's a bit tricky is sometimes it's not just sold as milk thistle, sometimes it's an ingredient out of six ingredients in a product. So, I always say, when you pick up any medication, just take a glance at the active ingredient. And then you'd be surprised what's hidden in the fine print. Please pay attention to that.

32:18  There is conflicting data about whether saw palmetto helps patients with prostate cancer. Saw palmetto, very popular in the setting of prostate cancer or enlarged prostate glands. Of course, there is data that has shown a decrease in the size of the prostate gland in patients who have BPH or benign prostatic hyperplasia. And also there are cases or studies that have shown that for patients who actually utilize Saw Palmetto, there has been a decrease in tissue uptake of testosterone, which of course drives the major concern with prostate cancer.

So, yes, there is some truth, but to be honest, there's also conflicting data. We just have to have full disclosure, really let your health care providers know what you're taking, so that way we don't run into any complications. But with Saw Palmetto, conflicting data says, yes, works great in patients who have an enlarged prostate. But at the same time, there has not been any claim or any data that is supporting its use in the treatment of prostate cancer.

33:31  There is no evidence that saw palmetto improves survival after chemotherapy or radiation. However, I know multiple patients who take it with the hope that it could make them respond better to chemotherapy or radiation. Now having said that, there are studies that have shown that patients who take Saw Palmetto may have increased sensitivity to radiation. But the truth is in terms of looking at the survival outcomes, there's just no clear benefit. There's no benefit. So, we need more information. We need the backing of the FDA. We need the backing of multiple trials before we can actually come out to say that these medications will work for us.

With Saw Palmetto, there's the concern with blood thinners. The drug-drug interaction due to increased risk of bleeding. So, we always want to pay attention to a lot of these medications, particularly if you're on other medications for the treatment of other conditions.

34:28  Studies have shown turmeric is effective in reducing inflammation, but it can also reduce the effectiveness of immunosuppressive drugs. Turmeric, also another common one. Turmeric has pretty good or interesting data in terms of treatment of infections, reducing inflammation. To be honest, there is a substantial data out there. But at the same time, there is no clear data that has shown increased survival in patients who have received this. And to be honest, there is some level of conflicting data. Some studies showing lack of benefit or no benefit, and then other studies that have shown benefit in terms of treatment of infections or through reducing inflammation. A take home point in this slide is a lot of products out there contain turmeric.

Also of course, patients or caregivers who like spices, this is a very common spice that's being used in cooking. When you look at the data out there, it really depends on the preparation. You buy turmeric as a spice for cooking. Well, you have to look to see where exactly it's being manufactured. Is it something you buy online? I am very skeptical about products bought online, particularly stuff that you have to ingest. Because that's a huge risk that no one should be willing to take. But with turmeric you want to watch out because it does get metabolized in the liver. So, there is concern for drug-drug interactions. There is the concern, particularly with patients who are on immunosuppression that you could interact with the therapeutic levels of your immunosuppressive drugs. So please number one, always let the pharmacist know, always let your physicians know. And let's make sure that we prevent any complications from happening post-transplant.

36:25  Valerian is popular for managing sleep problems, but may interact badly with other drugs metabolized by the liver. Valerian, very popular for the management of insomnia, lack of sleep. There's data, again: conflicting. There are also reports of very interesting side effect profiles, depression, diarrhea, dizziness, sweating, possible end organ damage. But what we do know for sure in addition to the side effects reported is that it does have some level of effect on the central nervous system. So, you will see a lot of products will say patients should not operate heavy machinery while taking the valerian, or watch out if you feel dizzy to prevent falls. All these are our signs telling us, yes, there is some activity in your CNS but not enough to come up with these reported uses for treatment of anxiety or treatment of insomnia. There's just not enough data for us to recommend this as a potential treatment option.

I mentioned before, warnings generally would have avoid operating heavy machinery, avoid use in pregnancy, lactating women. And of course, pay attention to patients who are already taking medications that are metabolized in the liver. You really want to avoid the use of this medication.

37:49  CBD Oil is widely available but, so far, it is only FDA approved for the management of epilepsy. And of course, the new kid on the block: CBD oil. If you look, maybe it's in Miami because Miami is crazy to be honest. But you can't go down the street and not see a sign that says, CBD oil available here. It's everywhere now. Actually, my parents live in Nigeria. My mom sent me a WhatsApp message the other day with a picture of CBD oil and she's like, "Can I buy this?" I'm like, "No."

But honestly, this is a problem because we do not know how these oils are being extracted. We don't know what they're putting in and we don't know what they're getting out. So, there is that concern of potential contamination that can lead to death, contamination that can lead to end organ damage. But look at the claims that are out there: management of anxiety, inflammatory conditions, nausea, psychotic disorders, addiction management, seizures, pain.

Now, I will say this, the only CBD oil the FDA has approved is in the management of epilepsy, of seizures. So, that is a yes, because they have looked at the appropriate studies and they have seen the benefit. But in terms of the other indications, addiction management, psychotic disorders, there's still more that we can learn. We cannot advertise the use of CBD oil. And actually, there is a particular brand that FDA approved. It's not just any CBD oil that you see down the street. There's a particular brand that has been approved by the FDA only for the management of seizures.

39:39  Side effects with the use of CBD oil: allergic reactions, possible end organ damage, dry mouth, fatigue, dizziness. Of course, we want to avoid use when patients are on immunosuppressive agents or if you're on other medications that are cleared through the liver.

39:57  Why herbs and supplements metabolized by the liver are a problem for transplant patients. So, just to give you a brief overview, remember our first patient, Mr. Andrew, just to draw your attention to the potential for drug-drug interactions. Because a lot of these cannabinoid derivatives go through the cytochrome P450. Now forget about the words and the letters. The bottom line here is the cytochrome P450 pretty much drives any form of liver metabolism. So, when you hear cytochrome P450. we're talking extensive hepatic metabolism.

So, any medication or herbal supplement that goes through the same pathway that the chemo goes through, the immunosuppressive medications go through, the supportive care medications go through is a problem. This is the drug-drug interactions I'm referring to. Because if you plug the liver with these cannabinoids, these CBD products that we don't know where they're coming from, then when you do take medications that you actually need, either for the transplant or for supportive care measures, then we run into a problem; because they're all going to the same metabolizing organ. So, this here is a problem. Also, there are case reports, or there's data that has shown, that these cannabinoids can also affect the hormones in the body. This is very important data that I think we need to think about to see why this needs to be discussed.

41:31  Check label for all products in supplements: they may not all be included in the name of the product. Mr. Edward: So, he came in with a suitcase of herbal supplements. Now, of course, if you pay attention to the supplement facts, look at the herbal blend, the fine print: echinacea. Of course, the product was not called echinacea. You always have to look and see what really is in these products. Now, what is interesting is if you look closely at the warning, they were nice enough to let you know here, keep out of the reach of children. Forget that part, people with asthma and progressive conditions such as tuberculosis, leukemia, Collagen disorders, multiple sclerosis, AIDS, HIV infection, and other auto immune disease should consult with their physician before using echinacea. Also, caution is advised for transplant patients taking immunosuppressive drugs. This is the fine print.

Remember, echinacea is not on the face of the product. So, then you have to look and see what is really in there. And then of course, how many people actually go and read the warning? Not a lot. So this is them covering ground. This is to protect them from any lawsuits. But they put a warning for transplant patients. So, please keep this at the back of your mind.

43:01  Always speak with your doctor or pharmacist about herbs and supplements you are taking. General recommendations, please always speak with your transplant physician and pharmacist. We're here to help not judge. Consider and discuss non-pharmacological interventions. Avoid polypharmacy, using multiple drugs to treat the same condition or more conditions. Document your medication history, be a wonderful historian.

43:24  Memorial Sloan Kettering Cancer Center has an excellent database with information about herbs and supplements you may be considering. You help us make sure that there are no complications during this journey. And be informed. Actually, Memorial Sloan Kettering cancer center has an amazing herbal database for health care providers and also for patients and caregivers. And it's free. They show you pictures, they give you information, give you side effects. And of course, it's not for you to make a decision. It's really for you to be informed and then share your concerns with your healthcare provider. And also pharmacist recommended, always please stay active and happy. I know I've gone through a lot of side effects, a lot of you know, downers. But please, the goal is for you to stay informed, stay active and be happy because you've come a long way. You've gone through a very long journey, so you owe it to yourself.

44:23  Consider other non-drug interventions to relieve problems. Now, nonpharmacologic interventions: I actually just started yoga a week ago. I am not a yogi yet, but getting there. But you'd be surprised, the breathing exercises, the stretching, it does a lot really. Because sometimes from inside you heal the outside. So, I think these nonpharmacologic interventions, we need to really give them a try: exercise, music therapy, relaxation, therapeutic massages are definitely worth the shot.

Thank you so much. I appreciate the time, and I'll take any questions at this time.

45:04  [Moderator] Question and Answer Session.  Great. So, just to remind you, we'll take questions. And it is being recorded so that for people who cannot be here today, it will be provided for them later on. So, please raise your hand if you would like the microphone to come to you. Also, we have microphones up here. I'll go right here. Sorry, there's a lot of questions. This lady had her hand, she's the first one I saw. Sorry. Did you have a question?

45:31  [audience member] Is using ginger and turmeric in cooking safe. Hi, thank you for your talk, it was actually very informative. I don't necessarily take a lot of the things, I do take Muufri and stuff like that, but you mentioned things like turmeric and ginger. And especially being Asian, it's in a lot of our foods. Is that a bad thing or is that something that would be okay because it's not a high dose necessarily unless we might use an entire piece of an entire ginger. Or something like that.

 [Dr. Ibekweh] So, I guess two things. So, with ginger, when you buy fresh ginger from the grocery store and you make a dish, that's fine. Now, of course I'm not expecting that if you needed one, add 10, it's all in moderation. But that at least, you can get organic products, you can get, you know, fresh products and you can cook meals with that. That's fine.

My concern is the products that have been processed because that's the problem. We don't know how they are being processed. We don't know where they're coming from, to be honest. Because a package of dry ginger could tell you it's coming from Florida and it could be coming from, I don't know, Indonesia. No disrespect to Indonesia. But you understand what I'm saying. It all depends on the amount and also where you're getting these products from.

If you're on blood thinners, should you be taking foods that have very high ginger contents or high tumeric content? No, because we're concerned with the interaction with the liver, the risk of increased bleeding associated with this.

47:29  [audience member] Is ingesting CBD different from using it topically? Thank you for being here for all of us today, we appreciate that. Just a quick question in regards to the CBD, is ingesting different from topical? Like doing the CBD lotions for joint pain and stuff?

 [Dr. Ibekweh]I really should have mentioned that. That's a great question because there are gummies, there are brownies, there are vapes and their creams and oils. It's a bit tricky because if there is a potential for contamination.

For example, there are cases with other herbal supplements and cutaneous anthrax contamination, for example. Since I cannot vouch for how these products are made, there could be an irritant added. We wouldn't know. And if for example, there is a break in the skin either from scratching or whatever the case may be, then that is a potential pathway for that product to get into the bloodstream. So, when we can't vouch for how well these products are made, to be honest, I would not recommend any of these products unless it's FDA approved and then you get the stamp of approval.

48:57   [audience member] Is it ok to take herbs and supplements if you are not on immunosuppressive drugs? Just a quick question. You have mentioned a lot of these, don't take them with immunosuppressants. Now, if you're not on immunosuppressants and you're one, two, six, five years down the road, is it still risk factor or something to be-

 [Dr. Ibekweh] That's a great question. When you're not on immunosuppression then, yes, you don't have to worry about the drug-drug interactions. What you do have to worry about is the potential for end organ damage in case it does have a contaminant in it.

For example, the cases of lead poisoning. If you're not on immunosuppression, that's great. But there are other medications you can be taking on a day-to-day basis that go through the liver, I.e. acetaminophen. Even patients who are on other supportive care type medications. But my primary concern really, when I look past drug-drug interactions, is really the risk of contamination. Because if these companies are not using good manufacturing practices to make these products, it's scary thinking about how exactly they're making it and then packaging these products. I can go on in terms of what really could go wrong if they are not being regulated by the right governing bodies.

50:27  [audience member] Why doesn't the effectiveness of herbs and supplements get studied more by the FDA? I completely agree with you. It's one of my frustrations because through my journey, I truly believe one of the reasons I'm still alive is because of supplementation. Now, I've tried to stay away from a lot of the herbal, I do do a little bit, but I research the crap out of it and make sure it's organic and there's like one ingredient and sourcing and all that. I research a lot of that.

You're saying there's a lack of studies, and we all know who funds these studies. And it's the big pharma, and there's no money in ginger. So, they aren't going to fund these studies. The same thing with just vitamin supplementation. I just wish we could find some kind of, "hey, this is good, this is pure." Do you think that there will ever be a point in time when the government does go into the quality of some of these things without killing the product though too? Because as you said, oh, the CBD, there's one that's regulated. Well, that's not pure anymore. They added their pharmaceutical components to that because they couldn't trademark, patent CBD, because it's a natural thing. I know this is a big dilemma.

I guess, the future of it, because I don't see it as a consumer, I don't see anything changing. I don't see the government supporting clean supplements. I have end stage kidney failure, so I eat very well; but I need to supplement. And that's one of the reasons I'm off of dialysis. But yeah, here I have this thing where I have to research the crap out of everything because nobody tells me what's clean, and why aren't they?

52:33  [Dr. Ibekweh] Honestly, I still wonder why exactly the FDA has not gotten into the herbal dietary side. Now, of course, they are present; but unfortunately to a certain extent. Exactly, it's very reactive and not proactive. But I will tell you this, the CBD oil that they approved, honestly, they did not add any pharmaceutical product to it. What they insured is the purity, they guarantee that how CBD was extracted, it's pure. No harmful additives, no harmful ingredients. Now, of course, the FDA had to step in to guarantee that. And when they put their stamp of approval, then it's official. There's that rest and ease that comes with that because they know what they're doing.

Now, of course, outside of the CBD oil, there two other products or even three now that are derived from cannabis. There are THC-like products, like dronabinol that we use for nausea and vomiting. These have been in the market for years. You see in that case, yes, there are excipients added from the pharmaceutical company; but the active ingredient is pure. It's not done in someone's trailer in the middle of nowhere, it's monitored and done under good manufacturing practices.

54:12  New England Journal of Medicine article says herbs and supplements need to be studied more.  So, I will tell you this, I believe at the end of this month, the FDA, they're having a public hearing. They want to hear from consumers how they feel about CBD oil: what are their experiences and what they want the government to do, pretty much. And because it's such a hot topic now, I am pretty sure in the next coming years, the FDA will get pretty involved with a lot of these herbal supplements because in 2015, in the New England Journal of Medicine, they've actually published an article looking at ER visits and hospitalizations from dietary supplements.

The article even says it: it's not followed well, it's not well studied. We're not looking at this closely and we really should because people are being harmed. And unfortunately, we're acting after harm has occurred. So, that's very reactive, we need to take a very proactive approach. And I am very optimistic that eventually we'll get there, the FDA will get there because, as you've seen, this is a $7 billion plus industry. So, the herbal industry, they're making a lot of money from this; but they're not as loud or as well-known as the pharmaceutical companies. So, they've been slipping under the radar. It’s all about awareness and just knowing what you're purchasing from these pharmacies online. Online, it's pretty terrible. You really want to watch out for that.

55:48   [Moderator] Session ends. Thank you. Thank you Dr. Ibekweh for your helpful remarks, all of you for your excellent questions. And this will conclude the session.