Natural Medicines: Evidence in Practice: Toxic Yellow Oleander in Weight Loss Supplements: Recognize the Risk

Transcript:

This transcript is automatically generated.

00:00:03 Kelly Daniels

As few as two seeds can be fatal, yet this plant continues showing up in weight loss supplements.

00:00:09 Jeff Langford

Well, Kelly, it sounds like you’re referring to yellow oleander. Welcome back to Natural Medicines: Evidence in Practice. I’m Jeff Langford, a pharmacist and managing clinical editor at NatMed.

00:00:19 Andrea Stafford

And I’m Andrea Stafford, pharmacist and assistant editor.

00:00:23 Kelly Daniels

And I’m Kelly Daniels, content production manager.

00:00:26 Jeff Langford

And on the show, we’re going to cut through trends and marketing claims to bring practical, evidence-based guidance for real patient conversations.

00:00:32 Andrea Stafford

And in this episode, we’re covering what yellow oleander actually is, how it ends up in these supplements, and why it’s a serious concern.

00:00:40 Jeff Langford

And we’re also going to take time to dive into quality certifications because beyond that immediate safety issue, another question is what are practical tools to help patients find products that they can actually trust?

00:00:53 Kelly Daniels

Quick reminder, this podcast offers CE credit for pharmacists, pharmacy technicians, prescribers, and nurses. Log into your NatMed account and look for this episode in the list of available courses. And for disclosure purposes, the NatMed team has nothing to disclose.

00:01:09 Jeff Langford

Kelly, let’s dive right back into what you set up for us regarding yellow oleander. I feel like this may not be entirely a new story, though. We’ve been hearing about this showing up in supplements for a while, right?

00:01:21 Kelly Daniels

We have. This actually goes back to at least 2022, a physician’s case report involving a 23-month-old who accidentally ingested a weight loss supplement. The product was labeled as tejocote root, but it actually contained toxic yellow oleander.

00:01:37 Kelly Daniels

And this case prompted a huge investigation into several products, and unfortunately it hasn’t slowed down. In fact, the FDA just recently, this past August, issued another safety alert and added an additional list of products to the products to watch out for.

00:01:52 Andrea Stafford

And I think it’s worth emphasizing here that this risk spans a wide range of patients. On the one end, you have completely unintentional exposures, like the 23-month-old you just mentioned, Kelly.

00:02:04 Andrea Stafford

On the other hand, you have patients who are actively seeking a weight loss supplement, reading the label and making what they believe is an informed choice, and they just have no idea that yellow oleander is in it.

00:02:16 Jeff Langford

Yeah, and really just to kind of underline what you just said, Andrea, we’re really talking about products that are labeled as tejocote root.

00:02:23 Jeff Langford

But instead of what’s on the label, they contain this yellow oleander and it’s toxic. And the scale of this problem really is significant. Since 2022, at least 25 different products have been found to contain this toxic yellow oleander instead of what’s on the label. And it’s not just obscure products. Some of these are really sold by mainstream retailers and mainstream sources such as Amazon.

00:02:47 Kelly Daniels

So today’s episode covers a lot of ground, spotting these products, recognizing and managing toxicity when it shows up, and giving patients and clinicians practical tools to help patients select better quality products to begin with.

00:03:00 Jeff Langford

Let’s start, Andrea, and kind of tackle that toxicity piece right up front. Can you tell us a little bit about this yellow oleander?

00:03:07 Andrea Stafford

Of course. So yellow oleander, or its scientific name, Thevetia peruviana, is a flowering shrub that grows mainly in temperate and subtropical climates such as Mexico. And it’s actually a really pretty plant, Jeff. It’s yellow or there’s a dull orange trumpet-shaped flower there.

00:03:26 Jeff Langford

I love that description.

00:03:28 Jeff Langford

But it’s poisonous. Like every part of the plant, the leaves, the stem, especially the seeds and roots, contain these toxic cardiac glycosides. And ingestion of this plant has led to fatal poisonings. And when we say cardiac glycosides, pharmacy nerds like me are going to think, hey, that sounds like digoxin. And you’re exactly right. This plant has digoxin-like properties and its toxicity really is very close to what digoxin toxicity would look like in an overdose of that prescription med.

00:03:57 Kelly Daniels

Sounds very scary. And that brings me back to what I said at the top. As few as two seeds can be lethal.

00:04:04 Andrea Stafford

Yes, Kelly. And fatalities have been linked, like you said, to as few as two seeds and up to a range of 10. And this range really depends on several different factors. The variability in glycoside concentration from seed to seed, whether the person vomited after ingestion, and then just individual patient response.

00:04:23 Jeff Langford

And when you think about it in the context of an adulterated or misbranded supplement, the patient has no idea what’s in that product or that this yellow oleander is in the product they’re getting. And even trace contamination may be enough to cause harm. So really the takeaway is clear. There’s not a safe amount of this yellow oleander substance.

00:04:45 Andrea Stafford

And because Jeff had mentioned, these cardiac glycosides act directly on the heart. What might start as just this kind of mild stomach upset escalates to a life-threatening cardiac event.

00:04:57 Kelly Daniels

Yeah, and unfortunately, we do have a real-world case report to review that kind of puts this into perspective. And then sadly, it’s a fatal one. A 63-year-old female presented to the emergency department. She appeared drowsy and vomiting.

00:05:10 Kelly Daniels

She’d been taking a product that she purchased online. It was labeled Nuez de la India, but unfortunately it turned out to contain this toxic yellow oleander.

00:05:18 Jeff Langford

And that’s really why it’s important for us to talk about how that toxicity presents and what it looks like in clinical practice.

00:05:26 Kelly Daniels

Right. In her case, vomiting was the chief complaint, but are there other symptoms clinicians should watch out for? Are some more alarming than others?

00:05:34 Andrea Stafford

Yeah, that’s important, Kelly. So GI symptoms, including nausea, vomiting, and abdominal pain are often reported, which lines up with what the patient initially experienced, which was vomiting. But the real concern here is cardiac toxicity. In this patient, at the time of evaluation, she had a heart rate of 30 beats per minute, atrial fibrillation with a slow ventricular response on EKG, and a potassium of 7.3 milliequivalents per liter and acute kidney injury.

00:06:04 Jeff Langford

And that cardiac picture that you just described, Andrea, makes sense mechanistically. We’ve mentioned yellow oleander has these cardiac glycoside properties working like digoxin, and that inhibits this sodium potassium pump in cardiac cells. So it’s blocking the activity, this little pump in the heart cells. And when that happens, that can really lead to just this full array of rhythm abnormalities. It might be an extremely slow heartbeat like this patient had, It might be a heart block. It might be ventricular arrhythmias, which can be fatal. So lots of different things can happen on the EKG and toxicity like this. Often, that’s right alongside a very elevated potassium. And you mentioned that patient had a potassium greater than 7, which would be enough to be quite alarming on any ED presentation.

00:06:53 Jeff Langford

So what really looks like a GI complaint when that patient arrived actually was this life-threatening cardiotoxic event and it was just unfolding in real time.

00:07:03 Kelly Daniels

Yeah, that cardiac picture is very scary and obviously ultimately what made this a fatal case. But she also appeared drowsy. Is that part of the toxicity itself or is that something else going on?

00:07:15 Jeff Langford

Yeah, so it’s probably a little bit of the toxicity and it’s also a kind of in parallel to what’s happening to the heart, because it’s not pumping enough, so as we’re not getting enough blood to all the places that blood needs to get to, we start to get related symptoms like CNS symptoms like dizziness, drowsiness. Visual toxicity can also be part of the direct effect of the drug. So it’s a combination of direct toxicity and kind of downstream cardiac events.

00:07:41 Jeff Langford

But either way, these kind of findings, especially when we start to couple them with the cardiac symptoms, should be red flags and would want immediate attention in any ED setting. The second part of that, I think, Kelly, is that it’s really important for clinicians and patients who aren’t going to have all of that information. They don’t know what their heart rhythm is or their potassium level is, but we need them to be aware that these weight loss supplements have been contaminated in some cases with this tejocote, the Nuez de la India, or Brazil seeds or names that of products that have been contaminated. So if patients are using them and having unusual symptoms, that’s the red flag. Go get attention and evaluation.

00:08:25 Kelly Daniels

Yeah, absolutely. So once it’s recognized, I’ll say someone realizes, oh my gosh, I’ve taken one of these and they go and seek treatment.

00:08:32 Kelly Daniels

What is the treatment? What does that look like?

00:08:34 Andrea Stafford

So anti-digoxin Fab fragments are the reversal agent of choice, and that’s indicated for high-grade AV or sinus node block, those ventricular arrhythmias, or a potassium above 5.5 milliequivalents per liter. And that’s usually given intravenously with doses ranging from 200 to 1200 milligrams, depending on severity. But really beyond that, management also includes monitoring electrolytes, fluids and then treating that marked low blood pressure or heart rate.

00:09:08 Jeff Langford

And beyond the DigiFab, other supportive measures are obviously in play as well. Like in this patient, it would be appropriate to use insulin and dextrose, for example, to manage the hyperkalemia piece. And that’s certainly an important action when the potassium is severely elevated, greater than 5 1/2 or 6, for example.

00:09:28 Kelly Daniels

Yeah. Sadly in this case, those resuscitation efforts and advanced cardiac care didn’t help and this was a fatal case, which is a stark reminder of how quickly this can progress.

00:09:40 Jeff Langford

And that’s really why this early recognition is everything. We want to connect the dots very quickly in practice so that we can make a difference in the outcome.

00:09:49 Kelly Daniels

Yeah, absolutely.

00:09:51 Kelly Daniels

Okay, we’ve covered why this is serious, but how does a toxic plant like yellow oleander end up in a weight loss supplement in the first place? This is not something that most patients even have on their radar.

00:10:02 Andrea Stafford

No, and that’s a really good question, Kelly, and it’s primarily showing up in products labeled the tejocote, Nuez de  la India, or Brazil seeds like we’ve mentioned. And these are supplements marketed as a natural weight loss aid. And in our case specifically, that product was labeled Nuez de la India, which is a common name for candlenut, which is a completely different plant. However, yellow oleander seeds look similar to candlenut, which is part of how this substitution happens. Whether accidentally or intentionally, this finished product is then adulterated.

00:10:38 Jeff Langford

Okay, and I really think, Andrea, as we talk about that, we still have the question like, wait a minute, how does this happen, right? And I think we have to kind of turn back a minute or step back for a moment and think about how dietary supplements are regulated, what that process looks like in terms of managing those. And so if we think back, we talked about this in one of our episodes, a few episodes back regarding sea moss and there’s this Dietary Supplement Health and Education Act or DSHEA that governs management of dietary supplements. And in this case with dietary supplements, the burden is on the manufacturer to ensure their products are safe and that the label claims that are on them are substantiated.

00:11:19 Jeff Langford

And manufacturers are also required to follow what we call current good manufacturing practices or cGMP. But there’s not an FDA pre-market approval before the product hits the shelves. And that’s very different than prescription medication. So it lives in a different place. It’s a completely different regulatory process. And that’s part of the reason there’s this gap for things like this to happen.

00:11:44 Kelly Daniels

Yeah, so essentially we’re relying on the manufacturer to do everything correctly. And if they don’t, there isn’t necessarily anyone checking on that.

00:11:52 Andrea Stafford

Yeah, that is kind of it in a nutshell, Kelly. And there is data supporting that this is just a concern, a broader concern. There’s this analysis of FDA warning data that found unapproved ingredients in hundreds of dietary supplements, most commonly in products marketed for sexual enhancement, weight loss, or muscle building.

00:12:14 Andrea Stafford

And while this research focused on detecting undisclosed pharmaceutical ingredients, the underlying pattern is the same one that we’re seeing here.

00:12:23 Jeff Langford

Yeah, right, Andrea. So sildenafil showing up in sexual enhancement products and anabolic agents and muscle building supplements are certainly examples of what you’re talking about there.

00:12:33 Kelly Daniels

Yeah, I honestly didn’t realize how widespread this is, and I doubt many patients do either. It’s certainly not something that comes top of mind when you’re browsing the aisles and picking a supplement.

00:12:43 Kelly Daniels

But can you quickly clarify what adulterated and misbranded mean exactly? We’ve used those terms a few times now.

00:12:50 Jeff Langford

Yeah, those are good things to define, Kelly. Under the Food, Drug, and Cosmetic Act, a product is considered, quote, adulterated if it contains a substance that could render it harmful to health. So this is like the real definition. If it contains that substance that can make it harmful to health or if it’s made under conditions that don’t meet that cGMP or the good manufacturing principles we talked about a minute ago.

00:13:13 Andrea Stafford

And then misbranding is a little bit different. That’s when the label itself is false or misleading, or it doesn’t accurately reflect what’s actually in the product.

00:13:23 Jeff Langford

And so in spite of having these terms out there, Kelly, tejocote products with undisclosed yellow oleander really fall under both of those umbrellas. So it can be adulterated because there’s something harmful in it.

00:13:36 Jeff Langford

It can also be misbranded because the label isn’t right. So it isn’t telling you what’s in it. So it could technically kind of fall in both of those categories.

00:13:46 Kelly Daniels

Okay, so given the risk of ending up with something that’s adulterated or misbranded, and it sounds like that’s kind of high, is there anything that helps patients pick a more trustworthy product, a way to know if the label actually matches what’s inside the bottle?

00:14:02 Andrea Stafford

That’s where third party quality certification becomes a practical clinical tool. Some manufacturers pursue this voluntarily, but not all certifications are equal and they vary significantly in what they verify.

00:14:15 Kelly Daniels

Okay, before we dive into those specific certifications, what are they actually assessing?

00:14:21 Jeff Langford

Yeah, so there’s a couple of categories of things that are potentially assessed with these certs and at a high level, one thing they might evaluate is manufacturing practices and sources for raw material. Also, whether the label ingredients actually match what’s in the product. So there could be testing to confirm, does the label match what’s in there if we chemically analyze it? Are there contaminants in it when we do that analysis like heavy metals or pesticides or other risky substances?

00:14:50 Jeff Langford

If we do a batch to batch comparison, are things similar? Do we have the same amount of the same ingredient if we compare batch X to Y? And in some cases, these certifications may also look to see if there’s clinical evidence to support the supplement itself for different uses or indications.

00:15:09 Andrea Stafford

So not only are they assessing a lot, but how they assess matters and varies.

00:15:15 Andrea Stafford

Some will conduct annual on-site cGMP audits, others rely on a paper review of manufacturer-submitted documentation. For product testing, some purchase products off the shelf and send them to an independent lab, while others rely on the manufacturer’s own reported results. And then some certifications don’t include this product testing at all.

00:15:39 Kelly Daniels

So it sounds like those with the on-site audits plus an independent off-the-shelf test are the ones we would consider most comprehensive and rigorous.

00:15:48 Andrea Stafford

Exactly. And some people may already be familiar with a few of them and see these on labels, which is USP and or NSF. But Jeff, can you dive in a little bit deeper about those two?

00:15:59 Jeff Langford

Yeah, sure. So if we think about USP first, we’ve got a lot of little acronyms in this episode today, but USP is United States Pharmacopeia. NSF is National Sanitation Foundation. So we may have a USP verified certification or this NSF Contents Certified. Both of these certifications involve an annual on-site facility audit. So that was one characteristic that Kelly said was important, as well as that regular off-the-shelf testing by an independent lab. Second thing that Kelly said was important. So we’re getting confirmation of label accuracy. We’re checking for contaminants like the heavy metals that we mentioned. We’re looking batch to batch consistency. And there were kind of some additional variants of these certifications. So NSF Certified for Sport does all the things I just mentioned, but they had even more frequent audits and testing for banned substances, which would be important obviously to athletes.

00:16:55 Andrea Stafford

And then just to kind of plug this in here, there’s also ConsumerLab Quality Certified that conducts regular off-the-shelf testing, though it’s kind of without the full GMP review or that Good Manufacturing Practice review.

00:17:09 Kelly Daniels

What about botanicals specifically, though, since that’s our topic today? We’re discussing yellow oleander. Do any of these review botanicals?

00:17:17 Jeff Langford

Yeah, so there’s one called Empowered By Evidence or EBE. And this is a quality certification that we rate as being comprehensive. It focuses on the source of botanicals. It requires compliance with good agricultural and collection practices. And uniquely, it has this requirement for clinical trial evidence for a specific finished product. So Empowered By Evidence would be one quality cert that would be botanical focused, Kelly.

00:17:44 Kelly Daniels

Are there any certifications that we might not consider necessarily comprehensive, but they can still provide useful information?

00:17:51 Andrea Stafford

Of course. So programs like Informed Choice or Informed Sport and the BSCG certifications are all useful for athletes that are concerned about banned substances.

00:18:03 Andrea Stafford

Overall, they’re certifications that we rate ourselves as insufficient because they don’t confirm that the label ingredients match what’s in the product, and most don’t test for contaminants.

00:18:15 Kelly Daniels

So that’s a lot to absorb. I guess practically speaking, what do you think patients need to know?

00:18:21 Andrea Stafford

So we want to remind patients that supplements aren’t held to that same standard as our prescription medications. And when they do use supplements, kind of point them toward those products that we rate with comprehensive certifications like USP, NSF, EBE, or the ConsumerLab like we had talked about earlier, especially when in a high-risk category like weight loss or muscle building.

00:18:45 Jeff Langford

And Kelly, as you mentioned, there’s a lot to absorb in this section and I think this is where I love a chart or a resource to help me remember and keep all of this straight, especially like in the front line of clinical practice. So we do have that. We have a quality certifications chart. It’s a quick reference guide, practical teaching aid for that you can use to educate patients as well. So when they bring a supplement to the counter and say, what about this thing? Or what does this seal or certificate mean on it? If it’s not one that’s top of mind for you, this is a great place to dive into like, hey, that’s what this acronym means and what it tells us about quality.

00:19:19 Andrea Stafford

Plus, NatMed’s FDA Dietary Supplement Ingredient directory categorizes ingredients by adverse effects, safety concerns, adulteration, misbranding, and they are pulling from these FDA findings. And so like Jeff had mentioned, this nice chart, this is also presented in a chart fashion so you can quickly check whether something a patient is asking about has already raised flags. And we’ve linked both of those in the show notes below.

00:19:47 Kelly Daniels

NatMed also offers CE credit and our monthly newsletter. Listeners can save 10% off a new or upgraded subscription with code natmed1026 at checkout. Links are also in the show notes.

00:20:00 Jeff Langford

Well, before we close, let’s bring it back to today’s main takeaway. What does this mean in clinical practice? So, like, if a patient comes in, mentions tejocote, Nuez de la India, or Brazil seeds, that really should be an generate an immediate conversation about a concern for contamination with yellow oleander, and I would steer people just proactively away from those products due to that potential risk.

00:20:25 Andrea Stafford

And we also want to know the toxicity picture. So those GI symptoms may be the first sign, but the cardiac concern is what makes this dangerous and early recognition is key. And we’ve linked the FDA warning page specifically in our show notes below so that you’re aware of some of the other products that yellow oleander has been found to be in.

00:20:47 Kelly Daniels

Yeah. And this oleander scare can be a great opening discussion for just supplement safety overall and help steering patients toward products with comprehensive third-party certifications like we discussed today, USP, NSF, Empowered By Evidence, or ConsumerLab.

00:21:01 Jeff Langford

Absolutely. And quality certifications aren’t a footnote here, really. They are this tool that clinicians and patients can use to help find products or supplements of interest that are of higher quality and can be a tool for product selection.

00:21:17 Andrea Stafford

So to claim CE credit, follow the instructions linked in our show notes.

00:21:22 Kelly Daniels

We’ve also included a link to the newsletter article on this topic and our full quality certifications comparison chart.

00:21:28 Jeff Langford

Follow and subscribe to this show in your podcast app so new episodes land automatically.

00:21:33 Andrea Stafford

Thanks for listening to Natural Medicines: Evidence in Practice. Evidence, not hype.

00:21:39 Jeff Langford

See you next month.