Transcription
[Music] welcome again to aija connected, the aha's online patient conference. my name is craig lammert. i'm a hepatologist at indiana university, but i'm also the executive director for the autoimmune hepatitis association.
our research group here at indiana university has found that many patients decide to use complementary and alternative medical strategies to treat some aspect of aih. and we've found that some of these strategies, that include agents taken by mouth, but also physical strategies such as yoga and meditation, can be helpful for some patients. however, most of these have never been scientifically studied and theoretically could have risks.
in order to learn more about these, i'm pleased to introduce to you dr. victor navarro. he's a professor of medicine at einstein healthcare network, where he's also the chairman in the division of hepatology. dr. navarro is also an expert in drug-induced liver injury. he's authored numerous scientific studies about the use of supplements and their risks in patients with liver disease.
dr. navarro, thank you for joining us.
hi everyone. my name is victor jay navarro. i'm the paul j. johnson chair for the department of medicine at the einstein healthcare network in philadelphia, pennsylvania, and i'd like to thank dr. lammert and the other organizers for inviting me to present to you today.
a little bit about me, i'm a gastroenterologist and hepatologist, also a transplant physician. and i see a lot of patients who have autoimmune liver disease, some who i suspect are in the audience today. but i have found over the 25 or more years in practice that it's one of the most gratifying diseases to treat, albeit a challenging disease for patients to manage.
so, what i've been asked to do is to talk about herbal and dietary supplements for autoimmune liver disease, and and i thought i would broaden the topic as as you'll see in these slides. so i'm going to share my slides here. and now you're seeing again my title, which is herbal and dietary supplements for autoimmune liver disease. and i will proceed.
and the first thing i'll do is give you an outline for my talk. and i have uh three guiding questions that i'd like to focus on and hopefully end up with some practical advice. what are dietary supplements and how are they regulated? could supplements be used for autoimmune liver diseases? are dietary supplements safe? and finally, some practical advice.
but before i get too deep into it, i want to make sure that everybody knows that dietary supplements or herbals, as you know, many people regard them, have been around for thousands and thousands of years. but in the united states, actually, the native americans were big users of herbs for medicinal purposes. but it wasn't until the shakers came along and really turned herbs into a commodity, something that could be defined as having a specific medicinal purpose and compounded and given to people.
the shakers, we all know, create really cool furniture to this day, but they were among the early sort of industry of herbals as medicinal plants. in the early 1800s, they used to create a compendia of herbs that are used for various health reasons. and in fact, they were the early compounders. they would extract herbs, the essence of the herbs, and they would turn them into medicinal products that would then be marketed to physicians called eclectics. and these were doctors that embraced the possible benefit of herbal remedies and became available also to consumers.
and we all know, of course, that there really is value in herbals. many medications that were transformational throughout our field came from herbal remedies. digitalis, as an example.
well, let's back up a little bit now and talk about how regulation exists for dietary supplements nowadays. supplements really are regarded by clinicians as things that are intended to supplement something lacking in the diet. often oftentimes, they're used for more than that, but that's really what a supplement is supposed to be.
often, you will hear us doctors, even patients, refer to these supplements as hds, or herbal and dietary supplements. but that's not really what the government recognizes as the correct regulatory term. the correct regulatory term is dietary supplement. and a dietary supplement has ingredients, and those ingredients are defined by law. the law, which is pretty old now, is called the dietary supplement health and education act, or the dshea of 1994.
that law defined dietary ingredients as vitamins, minerals, herbs, amino acids, and any concentrate, metabolite, or extract thereof, pretty broadly defined. as part of this law, the manufacturer attests to the safety. they don't have to prove it. they only have to attest to it, say that we have no reports of adverse events, for example.
now, as part of the law, a manufacturer cannot say that a supplement cures disease. rather, they can give what's called a structure and function claim. for example, calcium builds strong bones. and maybe that's for a calcium product. there's no statement that the calcium heals or cures osteoporosis or treats osteoporosis. however, the consumer is left to infer that because calcium is good for osteoporosis and it's contained within the product, you can infer that that product builds strong bones.
there are also standards that are defined by the law for purity, strength, and composition of a product. now, if you look across the globe, most developed countries, and even some underdeveloped countries, have regulations for dietary supplements, very different from the regulation for drugs. but those regulations may differ from country to country, region to region. but if you were to find one common thread among all the countries that have regulations for dietary supplements, most, the most common uh thread connecting them all, is a history of safe use. that is to say, that these herbs that are used in supplements have been around a very long time and have, just by this test of time, have proven to have proven themselves to generally be safe. so that's one of the common features of regulations across the globe.
now, in the united states, um, sorry, that slides might not have been catching up with me. i apologize. in the united states, there are uh, there's a regulatory body that oversees that regulation, and that's called the u.s. food and drug administration. the u.s. fda has two major arms: the centers for food safety and nutrition, and the center for drug evaluation and research. cfsan, the center for food safety and applied nutrition, is that body which oversees regulation of dietary supplements according to that law. it's also the group that receives any reports of adverse events from consumers or providers if a supplement is thought to cause harm. and that the mechanism by which those reports are sent to the fda is through something called medwatch.
now, the supplements are regulated very differently than drugs. drugs are regulated by the center for drug evaluation and research, and manufacturers of drugs are held to very different standards than manufacturers of supplements. in a drug, a manufacturer has to first prove safety and convince the fda that their drug is safe in the vast majority of people. and if it's, there's anything that could be potentially unsafe, that has to be known. that risk has to be known, quantified. the other thing is that they want a drug to be proven effective. so, one, safe, and second, effective. that is, there's a disease process that it will treat, cure, or manage.
now, what, where do we really stand today as regards dietary supplements? is the bottom line is that they're very commonly used. this graph from a very trusted source, which i give you on the slide here, shows you that for various age groups over the age of 20, we can see that there has been a general trend, increasing trend, in the frequency of use of supplements. and if we look at the group in 60 and over, that has the highest percentage of users, and the lowest percentage of the patients between 20 and 39.
now, the truth is, is that most of the supplements that are used and counted here are multiple vitamins, things that we use for maintaining our, you know, health on a daily basis. example, centrum silver, those sorts of things.
now, the reality, though, is that most supplements, most products are multi-ingredient mixtures. let me go to the centrum silver example. there are actually a lot of vitamins and minerals in that product. so it's a multi-ingredient mixture. and also, a lot of the mixtures, or a lot of the products out there on the market, actually are multi-ingredient. even if it has on the label, for example, i can actually sometimes there are other things in that, um, in that bottle, and that you would see that on the label. and sometimes they're fillers, sometimes they are, um, inert materials that have absolutely no nutritional value, or sometimes there are other herbs that are present in just much smaller quantities.
but the reality is, is that most products that are available are multi-ingredient mixtures. and many times, multiple herbal and dietary supplements are used concurrently. and they're used for many reasons. and research shows that people take these for self-empowerment, to feel that you've got some control over your own health, as well as disease. so they're used for disease self-management and prevention of disease. we've seen this in covid, where certain products, one which we'll focus on today, has really gotten a lot of attention as something that could actually prevent infection, or or maybe soften, or or or decrease the severity of infection.
people use them to promote health, physical enhancement is a big deal. power, you know, power lifters use, uh, bodybuilding products or performance-enhancing supplements. and sometimes there's dissatisfaction with conventional treatments. but one of the things that i find most concerning is that providers may not be aware of a patient's use. and i think that's in part the providers who don't ask. and sometimes, if they do ask, or even if they don't ask, patients won't volunteer that they're using them for various reasons. i think that that is a mistake.
now, let's focus on supplements for autoimmune diseases in general, and liver diseases, a little bit more specifically. you know, when you, when you look at the literature, there are, uh, there's a lot of work, there are a lot of studies which explore the possible value of supplements in treating diseases, certainly autoimmune diseases, but in general. animal models are a good start to look for whether there is the possibility that any product might benefit humans.
well, we know with animal models, with different types of products, different types of agents, curcumin, one we'll look at today, a few others, vitamin d, that that many of these products that you'll find on the market have been shown to reduce liver enzymes. and i'm sure many of you are very, very familiar with liver enzymes and how they reflect injury to the liver due to anything, let alone autoimmune disease. and there are even some products out there that have been shown in animals to improve hepatic inflammation and fibrosis, or scar tissue. and of course, if we can improve fibrosis or inflammation, we can actually prevent the progression of liver disease.
when you look at the human studies, however, sometimes the results are not quite as convincing. in fact, oftentimes, the results are not quite as convincing. and there are many reasons for that. but what i did is i started to get a sense of the universe of what's being done. i went to something called clinicaltrials.gov, freely available to you all to look at. and that allows you to search for many different things that you might be interested in. and i entered the search terms, as you can see, general health, liver, herbal supplement. and what i found is that currently or recently, there were over 30 studies with supplements on general health. and i found that there were over 300 when you enter liver disease as a search term, of products that were being studied for liver disease, ongoing or recent. and that's a lot. so that tells me that there's a lot of interest in this area to prove that supplements might benefit patients, particularly with autoimmune disease.
but before i focus more on autoimmune disease and how supplements may be a benefit, i want to point out why we would even think that a supplement could be a benefit to people. well, the reality is, is that many extracts have biological activity. and in a slide or two, i'm going to show you really what i mean. but i want to show you also some of the things that come out of my search of the literature, because in reality, there are signals here. and a signal is something that a clinician or a scientist will look to to say, well, maybe there's a potential benefit that we've got to study more.
so i have on the table listed here several products. in the leftmost column, betaine, carnitine, glycyrrhizin, omega-3, resveratrol, vitamin e. i'm sure you've heard of some of these. and there is listed here the proposed mechanism of how they work. now, we're going to focus more on two or three particular products so that we can think about the mechanism and how it might be a benefit to patients. but various agents function, we think, in various ways. they might be called what's called a methyl donor, which is very actually valuable to reduce inflammation. they might decrease fatty acid oxidation, which also decreases inflammation.
i like to always refer to vitamin e as a supplement where there really is very good data now to show that functioning as an antioxidant, it helps patients who have something called nash, non-alcoholic steatohepatitis, particularly in non-diabetics. and you can see that that's a common theme where supplements have been tested. but there are also been supplements tested for hepatitis c and liver cancer, hcc.
now, here, what i've done is i've summarized the outcomes of the studies that have been done on each of these. and you can see here, and this is in humans, that some products have shown no improvement in both liver tests, the lfts, or a biopsy. some have actually shown improvement in the liver tests and had an improvement in something called the nas. this is nafld activity score, nash activity score. this is the amount of inflammation on a liver biopsy for patients who have nash. here, you have glycyrrhizin that has improved liver tests but no effect on the viral hepatitis c. and on and on.
and vitamin e is a good example because there's been really high-profile studies that have shown a real improvement with vitamin e in patients who have non-alcoholic steatohepatitis. but in many of these cases, there's conflicting data. and i'll show you an example of that. but i want to go back to the statement that i made that many products have biological activity. and i'd like to show you what i mean.
these are two products that have been studied a lot for many diseases, um, and for general health. now, why is that? well, i put arrows on the component of these chemical structures which we really focus on as having antioxidant potential. these are called hydroxyl groups. now, why are antioxidants of value? whenever there's tissue under stress, it could be because of fatty liver, which in and of itself causes inflammation. it could be from autoimmune disease, which triggers inflammation. it could be from alcohol, anything that causes inflammation in a tissue causes the regeneration or liberation of something called free radicals. free radicals result from the breakdown of oxygen, and those free radicals are very injurious. but those free radicals can be what we call scavenged, or sucked up and neutralized, so to speak, by these hydroxyl groups.
so many of the naturally occurring supplements are exploited because they have all these hydroxyl groups and they function as antioxidants. milk thistle and green tea extract are two particularly that have gotten a lot of press. milk thistle for the treatment of fatty liver, and green tea extract for many different things, especially for, um, obesity, although not that that's necessarily an inflammatory condition, although some people feel it is. but these are two really important products.
now, i'd like to show you what i mean about the challenges we face when we focus on a supplement that has good scientific basis for potential biological activity, but how sometimes things just don't pan out when we study them in humans. and of course, one would ask, why?
this is a study that i did and published with several of my colleagues, funded initially by the national institutes of health, and then by the makers of the product called legalon. i'm sorry, this is a phase one and a phase two study. phase one studies are really intended to prove that something is safe and it doesn't cause side effects. and we proved that at certain doses. and then we went on to do a phase two study to show that a product actually helps patients and still is safe. and this product, silymarin, we took 78 patients, and they were randomized into three groups, and they didn't know what they were getting. patients got either a placebo, which was a nothing pill, a water sugar pill, or a dose of legalon at 400 or 700 milligrams.
and what we find is that if you consider this, no drug versus 400 and 700 milligrams, you could say, well, there is kind of an increase from nothing to 400 to 700 milligrams. but the reality is, is that this change in real practice was so minimal, we really couldn't conclude that silymarin was of any value for patients with non-alcoholic steatohepatitis.
and one asks, well, why is that the case? why did that happen? well, first of all, we accept that many products on the market have biological activity. but the problem is that, and the reality is, is that we're not dealing with drugs. we're not dealing with something that has been manufactured in the lab and tested in animals specifically without any other interruption, without anything else to, let's say, muddy the picture. in a, in a lab, we have a drug that is a candidate, and that, sorry about that, and that candidate is purely a chemical. and if we put it in an animal and then test it in a human, we know that it can only be that chemical, a, causing an effect.
with a natural product, we're dealing with not only with silymarin, but in there might be some variation in the concentration of the silymarin. there might be some other nuance because these are grown naturally that we can't predict. because these are not manufactured in the lab, that might affect how it behaves in humans. so those, those are at least two reasons why a lot of times the supplements don't perform in humans as a lab would, as it would if it were a chemical ingredient being manufactured in the lab.
that being said, there have been various supplements that have have been studied and remain under study for autoimmune disease. one of the, one where the, one of the supplements where i think there's really quite good basic as well as clinical evidence is vitamin d. but i want to focus a little bit on this other agent called turmeric, or its derivative curcumin. and you may see either or on the shelf. it's a spice, um, it's used in many countries, particularly in south asia, in southeast asia, and southern asian countries, south asian countries.
but we know that from a chemical perspective, it has antioxidant potential. it has those hydroxyl groups. but also, it's been, uh, written about as potential with for its potential as an antioxidant, as well as an anti-cancer drug, even to function, uh, as an anti-infective. but it's also got a, gotten a lot of attention for its immune modulatory abilities. that is to say, to harness an immune system that is acting out of control.
in what studies, or sorry, what disease processes has it been studied? there's quite a lot of work being done in rheumatoid arthritis and diabetes. in our own field, there have, there were some very exciting studies that came out now about 10 years ago about curcumin and its benefit in patients who have inflammatory bowel disease, particularly ulcerative colitis, for its ability to potentially induce remission, to control the disease, and to keep the disease under control. it's also been studied in brain diseases, and that's, those studies are ongoing, alzheimer's, parkinson's, huntington's, and multiple sclerosis.
but back to the ulcerative colitis story, because it really was captivating when this first came out, to have a supplement like curcumin that we might find useful for patients with a disease so difficult to manage as inflammatory bowel disease. well, one of the best levels of evidence, we call it one of the best studies out there to tell us whether an agent, a treatment, is of any value, is something called a meta-analysis. over the course of time, enough, what we call randomized controlled studies, which we think are close to the gold standard, come out to talk or prove that a product, an agent, a pill, is effective for patients. once enough of those studies come out, the proof of the pudding often is the meta-analysis, which takes all those randomized controlled trials, selects some, or those that are really good quality, that have been done well, and tries to assemble the data and distill it to a conclusion. and that's what this was.
this was a meta-analysis of studies of curcumin for causing a clinical remission in ulcerative colitis. and so they, uh, these authors collected the studies, selected those that were well done, and arrived at this diagnosis, and that is, based on the current available evidence, oral curcumin administration does not seem superior to placebo in attaining remission in patients with ulcerative colitis. and you can see that came out just a few years ago, and it kind of tempered our enthusiasm about curcumin in ulcerative colitis. but scientists, as they are, will not give up. we know that curcumin and other products have biological activity because of their chemical structure, and we will continue to explore.
so i wish i could give you much more on products that have been used for the immune system, and there are many products. but i'm, i'm loathe to list those for you because of the lack of, of clinical evidence to say that they could be of potential benefit. so hopefully, with that statement, i'll move on with some degree of satisfaction to the next, and then some practical advice.
so, are dietary supplements safe? well, in general, i must tell you that dietary supplements are safe. i say that because they're used in many forms by many people. sorry, i'm on an auto forward here. they're used in many forms by many millions of people. and so the fact is, is that, you know, people tolerate these, and the frequency of adverse events, or people getting sick, is really rather small. we know that because of the number of reports. and you know, if you do the simple math, if millions and millions of people are using these products, but you know, hundreds of thousands are not falling ill, and, um, then that tells you that they probably are quite safe.
although, of course, we all know that there have been reports of supplements causing liver injury. and here's one list that i've compiled of supplements that have been studied and have been reported to, um, cause injury in humans. green tea extract. i showed you the chemical structure. well, why would green tea extract cause harm? well, i told you and showed you that its chemical structure has a lot of those hydroxyl groups. and those hydroxyl groups, in theory, are good. they mop up the free radicals, those little agents that are released when tissues become injured, that can go on and perpetuate more tissue injury. but chemists will tell you that if you have a system, a biological system, that is has an abundance of hydroxyl groups, eventually those hydroxyl groups will sort of act on one another and start to generate free radicals all by themselves. so, in theory, too many of these hydroxyl groups in a biological system can cause liver injury.
so that's the story about green tea extract. is we think that too much green tea extract can cause injury. the other thing is, don't confuse some of these extracts with the real compound. for example, curcumin. if i were to show you curcumin, it's a powder, and it's got a lovely color, and it's a really good thing to cook with. but it does not look anything like the curcumin you'll buy in a store, which is in a pill form. likewise, for green tea extract. you won't recognize the tea that you drink in the morning or throughout the day as what people are taking from the health food store to lose weight, because it's in a pill. and the reality is, is that like the shakers, now we've got commercial entities which are identifying these products, these agents, these urns, and compounding them and making them into pills, which could potentially have really high concentrations of, yes, what is in essence a good product. but if it's given to somebody in really high concentrations, or taken under the wrong circumstances, it could cause harm.
well, again, that green tea story, extract as a potential cause for harm, can be said for just about anything on this list. some of you may be familiar with some of these. kava, which has been used to help sleep. black cohosh, for menopause. and i'm not saying you can't find these on the shelves. you probably can. but we have case reports that are pretty convincing that many of these, or that all of these, have led to injury of the liver in humans.
why then does this occur? well, i've described for you the story about green tea extract, and we call that direct toxicity. there's something about the product itself that injures tissues, and the liver, especially, because most of what you eat ends up being absorbed into the liver. but there's a, there are other reasons why products can cause harm, and we'll talk about adulteration and contamination. i actually have a case i'd like to share with you. there's also the inappropriate use issue. and i find this happening commonly with weight loss products. um, and many of the weight loss products contain green tea.
now, what am i really talking about here? well, we all feel that these gen, that dietary supplements are generally safe, and they're natural. um, but i think what the mistake we make is, we assume that a safe, natural product can be taken in abundance and cause no harm. and that may not be the case. so if someone, for example, were using a supplement that contains green tea extract, but assume that it's safe and it's natural, or it's natural, therefore it's safe, then taking one pill, which might be recommended on the label, maybe taking five is even better. and maybe taking five while i'm fasting to lose weight is even better than that.
well, in reality, we know that taking green tea extract on an empty stomach and in abundance will increase the levels of the chemical component of green tea extract in the body and can predispose to harm. that's been shown in animals, and we suspect it to be the case in humans. so inappropriate use is another. we know that some herbs can interact with drugs. st. john's wort is an example. and finally, one of the most interesting things is individual susceptibility. that sometimes there are genetic factors which actually can predispose a patient to experience liver injury.
well, now i want to show you a case. this case illustrates one of the reasons, um, of of how products, how supplements can cause liver injury. this is a case from our drug-induced liver injury network study. it's anonymous, so, you know, the, some of the details have been changed. so it's, you know, as i said, it's anonymized. this is a 24-year-old previously healthy patient who was hospitalized with jaundice. and we undertook an evaluation for non-drug causes, which was negative.
now, that's important because i know many of you are aware of what liver injury is and how it may make you feel. we diagnose it at the outset by elevated liver tests, which you see here. the alt, which normally is 30 or less, here you see is almost 10 times abnormal. the bilirubin, which is normally 1 or less, is five or six times abnormal. so this is how we, as clinicians, in addition to symptoms, diagnose liver injury. but not all liver injury is due to supplements or pills. we have to be very careful and take a very cautious approach. for example, in a patient who has autoimmune liver disease, i guarantee you that before your diagnosis was made, you've had an imaging study to rule out a gallstone or a tumor or cirrhosis or something else. and you've also had blood tests to rule out viral hepatitis and things that might have been inherited in the family. and you probably, um, even had a question, series of questions asked of you of what other medications you might be taking, because in reality, some medications can even trigger something that looks like autoimmune liver disease.
but nonetheless, before we ever make a diagnosis, we go through, we clinicians go through, whoops, a steady series of tests to make sure that we've got the diagnosis right. we did that in this case. and this patient reported taking something called tamoxicloam. now, you can see here the course of the patient's injury from 0 to 31, where the liver tests were elevated, he was jaundiced, and that jaundice continued even 31 days, although the liver tests improved.
what we do in our studies is we ask our patients to give us product that they might have taken or that they did take that we think might have been the cause for the injury. and we did that. that's the pill. and what we do is we send it to our analytical lab at the university of mississippi. and the first thing we do is we test to see whether what was written on that label was actually in the product. this is the label ingredients. nd means not detected. and that means that everything on that label was actually not in the product. this is a process called liquid chromatography.
now, what's really important here is something had to be in that product, because we were suspicious that that something was causing the patient to be ill. so the liquid chromatography gives us a reading that looks like this. it's a little spike on a run here. and we look in a library to see, well, what does that spike correspond to? it corresponds to something called tamoxifen. now, tamoxifen is used for, if you, you may know, is a, is a drug that's used for breast cancer, to prevent breast cancer in women who've had it, men even have had it. but we also know that tamoxifen can cause liver injury that looks just like what i showed you. so we make the conclusion that this patient had tamoxifen injury of the liver. but that tamoxifen was what we call an adulterant. it was nefariously included in that product for a purpose. and the purpose is really because this product, which was, um, we suspect, being used for bodybuilding, can sometimes, these products can cause gynecomastia. and this functions as an anti-estrogen, the tamoxifen, to prevent gynecomastia, breast enlargement.
that led us to the question of how common are these labels so inaccurate? so what we did in our study with the drug-induced liver injury network is we took the products that patients gave us that we suspected caused liver injury, and we did a very simple thing. we took all the labels when they were available, and we took the product, and we ran them through our machines to determine how frequently were those labels inaccurate. and the results were astounding. about 50% of the cases, our products had, had inaccurate labels. but the most inaccurate were those products that were used for bodybuilding, as you can say, 80% had products, or excuse me, ingredients that were in the product but not listed on the label. frequently anabolic steroids, products used for weight loss, and products that were used for sexual enhancement.
now, why am i giving you this information? i'm giving you this information because i want the consumer to be aware. and you, as whoops, and you as consumers with autoimmune liver disease, looking for a treatment that is natural and generally safe, should be aware that there probably are products and supplements out there that are operative in the immune system. i think we know what they are. i think we have to study them to understand how they work, why they work, and in what dose they will work. i wish we had that kind of information so that i could give you a list of agents and products that you could refer to. but i can't, because that information just doesn't exist.
we talked about curcumin, turmeric. and i'm really excited about it as a chemical structure, but also about the amount of research that's going on with it. and i'm sure that there are other products where you will investigate and find that there is also research ongoing that's very exciting.
so, what do you do with that information? and this is where i'll leave you with some practical advice. so, as you find things, and you should, you're informed, intelligent people with a disease process that is manageable, and you're constantly going to be on the quest for newer and better and safer treatments. but look to trusted resources. look to your provider. i think the contemporary provider is much more open to talk about the use of supplements than we they used to. we realize that they're used commonly, and we also realize that there probably is value. but most providers will also be able to help you navigate what is online through various search engines so that you can have a sense of, is there potential value? and if we think there's value, and if we assume that these products are generally safe, do we know anything about potential for injury, which might be a good reason to stay away from a product?
here's one online source that i think, and i refer my own patients to, this is the office of dietary supplements of the nih. and it gives you a pretty good overview of many supplements, and it's refreshed on a periodic basis. i'd also suggest that you stick to known retailers for various reasons. nobody, like these big retailers, certainly nobody wants to have their name tainted by marketing or by selling products that cause injury. in fact, some big retailers have even pulled products from the market when they become aware of, uh, of events that have, uh, caused harm to people. so stick to the known retailers. i tell my patients to avoid getting products from small, no-name retailers or abroad, where you might not really know what you're getting. and we've proven in our own studies that you don't sometimes know what you're getting.
use the products according to the label directions. i think they're there for a reason, mostly because they have told the fda, the manufacturer has told the fda, that if used according to our label, we don't have any reason to believe that they've, this product will cause harm. and finally, and probably the best advice that i could give is, if you're going to use a supplement, stop using the supplement if there are any unexpected symptoms, and contact your provider. that unexpected symptom might be worsening fatigue. it might be worse, yet jaundice or vomiting. or maybe it's just not having the anticipated benefit. don't continue to use it.
so i want to thank you for having invited me, dr. lammer, and the other organizers. uh, this is a wonderful forum for you to learn about autoimmune liver diseases, and it's been a real honor to participate in it. thank you very, very much.
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