Why your milk thistle label is wrong: Prof. Dezső Csupor, the full interview

Could you introduce yourself and your work, and tell us how you came to specialise in the quality of medicinal plants?

Well, thank you for this call. I'm Dezső Csupor. I'm a pharmacist and a professor at the University of Szeged, Hungary. Currently I'm the head of the Institute of Clinical Pharmacy. My original scientific background is pharmacognosy, so I was dealing with medicinal plant compounds, and I'm also a founder of a quality control lab for food supplements and medicinal plants. I started my career with the isolation and structure identification of natural compounds. But over time I became increasingly interested in what happens with these compounds in the human body. And also I was interested in the quality of the products that we are eating.

What drew you to milk thistle in particular?

For me, this is one of the most important medicinal plants, because it can be found on the market as a food supplement and also as a real medicine. And in some cases this is the first-choice treatment for many patients who are suffering from different liver diseases. So it is very crucial what quality of products they are consuming.

When a supplement label says silymarin, what actually is that? Is it a single thing or a collection of things?

It is very tricky, because in my view medical doctors usually think that this is a single molecule, similarly to several modern medicine products. But in fact silymarin is a mixture of different flavonolignans isolated from milk thistle. It contains several compounds with very similar chemical structure, all together more than 20. And also these are similar not only chemically but also in their biological effects. So therefore they are used collectively, not in a purified form, in the practice. Or almost always. There is one exception, because there is an intravenously used medicine which is for the treatment of mushroom poisoning, and those intravenously used medicines, they contain only one single pure compound isolated from this so-called silymarin.

So what does that matter for measuring it?

The whole problem is that we have to decide what we really want to measure. Is it enough for us to measure this complex mixture, silymarin, or do we want to measure these compounds separately? Previously the practice was that the silymarin was measured as a complex together, without sorting out the different compounds. But now we are moving towards the practice that we should measure its compounds separately.

And is that UV versus HPLC, essentially?

Yeah, because UV spectrometry is a quite simple and cheap method, but it has some limitations. And one of these limitations is that with UV spectrometry we can measure only the silymarin complex together. There are better methods by which we can measure these compounds separately, and then we can calculate the sum amount of these, and maybe the most widespread used methods to do this are HPLC-UV or HPLC-DAD.

So does the HPLC method give you a more accurate reading of what's going on in the plant?

Yeah, yeah. And this is what we also are doing in our lab, and this is what also the European Pharmacopoeia and also some other modern pharmacopoeias are using for the quality control of silymarin.

I think that's what I'm seeing in the industry: a lot of companies will claim a silymarin amount, but with a UV method, and then it gets tested with HPLC and it's a completely different number.

And usually what they measure with UV is a bigger number.

Than what it actually is. Because it's not separating the individual compounds. And perhaps could it be picking up things that are other than silymarin?

Of course. So this is the key of the problem, because some other compounds that have similar absorption to silymarin compounds, those will also be measured together with silymarin. So this is some kind of very severe bias, which makes the amount that you measure with UV usually higher, or much higher, than that you measure by HPLC.

So you mentioned that the pharmacopoeias have moved to HPLC because it's a more reliable method, and that's because they can identify the compounds.

Yeah. So the selectivity is important. UV spectrometry is not selective. HPLC is very selective, so you can measure the individual compounds.

Because I suppose if silybin A is one of the most powerful, and you had a milk thistle extract where silybin A wasn't present, or very low, then that would reduce the quality of the supplement.

Yeah.

My next question was what's the difference between HPLC and UV, but we've answered that.

Yeah, but maybe I have to mention that the key difference is that in HPLC there is not only spectroscopy but chromatography. Chromatography means that we sort out the compounds before measuring them. Spectrometry means that you measure what is there. So HPLC means high pressure, or high performance, liquid chromatography. So chromatography is there in HPLC, which is not there in the UV spectrometry. So this is a quite big difference.

You mentioned there are individual compounds within silymarin. Now that we're measuring them individually, we might find, as the research progresses, that certain ones are more beneficial or have a stronger effect on the liver. So identifying the presence of them is important for consumers to get the benefit they're seeing in the studies.

This doesn't seem a really important issue at the moment, because what we know about these silymarin components is that these are biologically quite similar. So their effect on the liver is very similar. But to be honest, the most knowledge is related to silybin. Silybin A is maybe the most thoroughly investigated compound, and it is not a mistake that silybin A is used as a pure compound in the medicine. So if you are taking it orally, you usually take silymarin, the complex mixture, but if you would like to use this plant intravenously, you will use only that one purified compound.

So they've actually made medicines based off silybin A.

Yeah.

Beyond the total count, does the ratio matter? Is there an ideal milk thistle plant with the right ratios, or can they vary a little bit?

There is not one single ratio which is the best one. But when we are speaking about measuring something by HPLC, this can be considered as a fingerprint. So an HPLC chromatogram is the fingerprint of an extract, and fingerprinting gives you some information about whether the extract, for example, is adulterated or not, or is it properly extracted or not, is it handled carefully or not. Because, for example, if there is some heat during processing, it might result in the decomposition of some compounds, which might lead to the decrease of some peaks, and some new peaks will be in the chromatogram. So it is very informative. So if you have experience in the analysis of a certain extract, for example milk thistle, after a while, when you look at a chromatogram, you will see whether this is a genuine and good quality extract or not. So this fingerprinting by HPLC is also important.

And you wouldn't be able to get any of that information with UV.

Yes, certainly.

You've helped pioneer the quality testing of supplements in Hungary. What did you find when you were doing all that testing?

We started this work in 2009, some years after the new food supplement legislation came into force in the European Union, and we started the first investigation with products that were marketed as sexual performance enhancers, because in the literature I saw that some of these products are adulterated with some medicines, for example sildenafil, which is the active component of one of the most well-known medicines on the market, Viagra. And what we found is that this really was there on the Hungarian market. The first investigation involved 10 different products, and six of these contained sildenafil, and the amount of sildenafil was much higher than that in the medicines. So that was shocking for me. And then we continued the work with slimming agents, with grapefruit extracts, with CBD products and several others.

That is shocking. So you've got what is supposed to be a natural supplement marketed for erection help, and they've snuck in essentially Viagra to make it work better, obviously completely illegally, and just to make their return-customer rate better, I guess.

Yeah, yeah. One product contained 200 milligrams of Viagra, which is double the maximum dose as a medicine. And this is extremely shocking, because some of the consumers who want to buy a hundred percent natural products, they buy it because the medical doctor tells them that you should not take Viagra because it might be dangerous for you. And then they switch to something a hundred percent natural which contains more Viagra than the medicine. So this is extreme.

The more I dig into the supplement industry, the more it feels like the wild, wild west. No standards. I really want to see the industry move forward, because the supplement industry is very limited in the marketing claims it can make, and as the decades go on we're going to get more research that shows certain natural things have benefits. But if the regulators look at the market and go, well, the actual chance of someone getting what's on the label is nil or very low, they're not going to assign the claims. So it's a huge shame, really.

Yeah, it's a problem. And the problem is with the legislation. For example, one problem is what you mentioned, the claiming. So it is nonsense that you are not allowed to write anything about the real effect of your product. So this is one serious problem. And another problem is that the quality control is not compulsory. So some companies care about this and they have their own laboratory. Some others also care about this and they send their products to independent laboratories. But there are unfortunately some companies who do not really care about the quality, and they just sell the product without knowing what they are really selling.

I agree exactly with what you said. It's almost like the industry is over-regulated in some areas and under-regulated in the areas where it really needs to be.

What are you working on now? Anything interesting?

Currently I am working also in the lab, and I'm also working with research which is related to the assessment of different natural products based on clinical trials. And I'm also organising clinical trials with medicinal plants. Speaking about the analytical part, we are developing and validating several different methods for the analysis of food supplements at our private laboratory. And one of the key issues today, I think, is the analysis of CBD products. At least in Hungary, CBD products are the top sellers, and many people are taking them without knowing the real composition. And it's surprising how different these products are in quality, I have to tell you.

CBD has never been something I've looked into too much, but that's interesting. So you're basically doing another investigation series on CBD specifically. I'll be very interested to see the paper.

We have some papers published, and some of those are related to pharmacology, and it was also very shocking. I don't want to repeat myself, but maybe this is the best word: we found that CBD has quite a remarkable effect on one of the channels in the heart, on one of the potassium channels, which theoretically might result in arrhythmia. And it was discovered, based on several clinical data, that people who are consuming marijuana, some of those are facing very serious arrhythmia, and there is no real interpretation for this phenomenon, but it might be related to this channel effect of CBD. So this is only laboratory work, but it might be related to the clinical problems with CBD.

That sounds serious. Well, thank you for all the research you've done over your career. A big part of what I'm trying to do is take people like yourself, with all this specific knowledge, and share it with consumers so they can make better purchasing decisions.

Thank you. Thank you for your interest.