Investigating Ginger's Place in Migraine Therapy

In this episode, we explore the ongoing debate over ginger's potential to treat migraines. By dissecting a recent systematic review asserting ginger's efficacy, we meticulously examine research methods, including literature searches and study quality assessments. Through our analysis of the data supporting ginger's purported benefits for migraines, we uncover inconsistencies and overlooked errors. Ultimately, our discussion serves as a cautionary reminder of the intricate nature of medical research and the essential need for critical evaluation when considering potential remedies.


L. Chen and Z. Cai, The efficacy of ginger for the treatment of migraine: A meta-analysis of randomized controlled studies, American Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2020.11.030

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Transcript

Introducer: 0:02

Welcome to the Dr Journal Club podcast, the show that goes under the hood of evidence-based integrative medicine. We review recent research articles, interview evidence-based medicine thought leaders and discuss the challenges and opportunities of integrating evidence-based and integrative medicine. Continue your learning after the show at www. drjournalclub. com.

Dr. Goldenberg: 0:31

Please bear in mind that this is for educational and entertainment purposes only. Talk to your doctor before making any medical decisions, changes, etc. Everything we're talking about that's to teach you guys stuff and have fun. We are not your doctors. Also, we would love to answer your specific questions on drjournalclub. com. You can post questions and comments for specific videos, but go ahead and email us directly at josh at drjournalclub. com. That's josh at drjournalclub.com. Send us your listener questions and we will discuss it on our pod. 

Hello Adam, how are you doing, sir? Welcome, welcome.

Dr. Sadowski: 1:13

I am doing good, Josh. How are you?

Dr. Goldenberg: 1:15

I'm doing great. I'm doing really great. You know what I'm disappointed about?

Dr. Sadowski: 1:19

Tell me.

Dr. Goldenberg: 1:20

Every time I come on with you, there is like this really fun, exciting, semi irreverent name that you have for yourself on the bottom of your screen and I always have to like try not to laugh at the beginning of the recording because it's like the most ridiculous things. And now it's just enter your name.

Dr. Sadowski: 1:41

That's what it is. That's what my name is. I put that in there.

Dr. Goldenberg: 1:46

I think that's the best one yet, but it's like the only one I can say on the air. And then, whenever we have technical issues, um, I want the listeners to to feel sad for me, because every time there's technical issues and I have to like reach out to technical support, they're like oh yeah, user, dot, dot, dot, dot dot is we've lost their audio and I'm like oh my god, it's so embarrassing okay, um, I didn't know that anyway, yeah, yeah, yeah, I've been covering for you this whole time, all right, um, this is our very professional podcast.

Dr. Goldenberg: 2:17

We have a listener request today, which is awesome. Um, do you know? You must know, Eric Yarnell right, Dr Yarnell.

Dr. Sadowski: 

I don't know of him of him.

Dr. Goldenberg: 2:27

Yeah, so, um, Dr. Yarnell is like big guru in the natural medicine world, particularly around herbal medicine and men's health as well, and gi space, also lots of things, and he was a professor of mine and he's also just been like super, super helpful. Like whenever stuff comes up like professionally, I'm like, eric, what would you do, type of thing, anyway. So, um, so he reached out. He's also just been like super, super helpful. Like whenever stuff comes up like professionally, I'm like what would you do, type of thing, anyway. So, so he reached out. He's like I read this paper and I think it's garbage. Can you confirm which is like I think, essentially what it was?

Dr. Goldenberg: 2:59

Let me see, I'm going to pull up the text here and so that would be a fun thing for us to go through. And okay, so this is. We'll put the link up on the show notes, but this is a systematic review and meta-analysis on ginger for migraine prevention and, for the life of me, I can't. Here's his. Do we have his questions? Specific questions? Why don't you start us off? While I try to track down his text? Can you start us off kind of describing it?

Dr. Sadowski: 3:33

Yeah, and technically it's not necessarily for prevention. The aims were to assess the efficacy of ginger versus placebo for migraine patients. They don't actually clarify if it is or not for prevention and based on their outcomes that they were looking at, it looks like it was used more so for an acuity standpoint. So if you were to get a migraine, how would you? You know how well would ginger work? Gotcha, Compared to placebo, not compared to Tylenol, ibuprofen, your sumatriptan, your risotriptan, so your triptan medications, not to the new CGRP agonist medications like Nertec. I know that's a brand name, but we have no financial conflict of interest here.

Dr. Goldenberg: 4:24

Right. So we've got this paper here. It says Meta-Analysis of Randomized Trials by Chen et al, and we'll again put the link Efficacy of Ginger for the Treatment of Migraine. Why don't we go through a quick methods of this and then we can go through Eric's questions and our own sort of critique of the paper as well. Does that sound good?

Dr. Sadowski: 4:46

Yeah.

Dr. Goldenberg: 4:47

Cool, All right, so let's jump in. So, listeners, like we like to do, we will usually skip through the introduction. Usually that will again just kind of set up the rationale, the arguments, the mechanisms, all of Adam's favorite things. But also what I was looking for is is there any previous literature on this? I was really surprised to hear that there wasn't a meta-analysis on previous meta-analysis on ginger for migraines, but it looks like there is not. And yeah, let's jump in. You want to kind of walk us through the methods and then we can kind of discuss them, maybe section by section as we go.

Dr. Sadowski: 5:26

Yeah, sure. So basically what they did was they looked for studies that had a randomized controlled trial design with patients who were diagnosed with migraine they did not specify how that diagnosis was obtained, and then the interventions were ginger versus placebo Great. And then what they used to quantify the quality of the study was your favorite Jadad scale, and that, basically, is a five-point scale where they defined anything less than a two or two or less to be low quality and anything three or higher to be of high quality. And what that Jadad scale consists of is randomization, blinding, dropouts and withdrawals, where you get zero to two points for randomization, zero to two points for blinding, and then zero to one points for dropouts and withdrawals, for a total of five higher scores or better.

Dr. Sadowski: 6:30

And then, basically, what they did for their primary outcomes, what they were looking, what their main outcomes were, were pain-free at two hours, which I think is a reasonable outcome, because if you think about when we're prescribing triptans, you know you would do an initial dose and then, if you're still having pain, you would repeat the dose at two hours and then that's kind of it for the day with regards to those medications.

Dr. Sadowski: 6:55

So I do think that that's a reasonable outcome to look at. So were they pain-free at two hours as well as what were those pain scores at two hours? The secondary outcomes were the treatment responses which were defined as you know. Did individuals get a 50% reduction in migraine attacks? And then, if they were to quantify their migraine severity on a pain scale of zero to four, which I thought was kind of odd and somewhat arbitrary, where the lower scores are better you know how much do they reduce their migraine pain by? They also looked at nausea and vomiting as a secondary outcome, which I think is reasonable because a lot of people get nausea and vomiting when it comes to migraines. And then they also looked at adverse reactions, which I also think is a reasonable secondary outcome, because you want to see if the intervention you're using is safe.

Dr. Goldenberg: 7:51

Love it, Excellent. Let's, before we jump into the results, let's. Why don't we go through and kind of give our critique of those methods? I can get us started with literature search of that first section, Just for the listener. Again, we're going to link to the actual paper, but just show you what I'm looking for. So this is the literature search section. So they searched multiple databases. So that's good. So PubMed Embase, Web of Science, Cochrane Library, et cetera, so that was really excellent From inception to September 2020. So I think this paper came out in 21. So, again, that's reasonable. Just knows, a little bit stale. It's a little bit few years behind, but that's totally fine.

Dr. Goldenberg: 8:33

The other thing that I didn't see was anything about gray literature searches, so looking for papers that may not have been in the main databases that may be relevant. I think that for herbal medicine, that may indeed be the case. You know there might be these smaller trials done that never made it to the proper databases. So a gray literature search, I think would have been useful. They didn't have any integrative medicine or herbal databases. So with a topic like this, you would think that you would try to look for some specific databases that are content specific. So I have a little bit of questions about if they caught everything. Also, there's no search strategy presented, just some keywords, which is not standard. Like you should be reporting that. So I guess in some my thoughts are, they searched a lot of databases but I don't think that their search was exhaustive and I think it's possible they may have missed a few studies. Any other thoughts on the searching selection criteria stuff?

Dr. Sadowski: 9:38

No, I think you nailed it on the head there. But other methodological things to also consider, just in general, is that did not look like this was a registered a priori, meaning they did not have their methods developed and then implemented it into a registry such as Prospero prior to doing this.

Dr. Goldenberg: 10:00

And yeah, yeah, that's, I think that's the biggest one. I did do an Amstar two on this paper, you know, looking for critical weaknesses, and yeah, that's, that's one of them. You, these days you must have a protocol registered a priori, and I don't think there was any protocol at all registered one way or another for this one. So that's sort of the major red flag there. And this, just on that alone, plus the search design, would be considered a critically low quality systematic review according to Amstar 2, which is sort of the standard accepted quality tool. So just off of the bat, eric, you're right, it is garbage. Technically we wouldn't call it garbage, we would call it critically low quality. Call it garbage, we would call it critically low quality.

Dr. Sadowski: 10:46

Yeah, and I think I think any like sort of modern day meta analysis that if they're using the Jadad scale, just stop reading it.

Dr. Goldenberg: 10:56

Oh yeah, Okay, tell us about that, Because that's that's a really good point. I was shocked when I saw that.

Dr. Sadowski: 11:00

It's like I haven't read that for the longest time. Yeah, I mean one. It's a scale, so it's kind of harder to get. There's a lot of subjectivity to that. How are you going to differentiate a five versus a four? Why does the randomization get two points? And how are you going to discern between a one point for randomization versus a two point? Would a two point get if they say exactly how randomization was performed? You know they use some sort of computer generation does that get two point? But if they say, oh, we randomized it but they didn't say, how does that get one point? So it's, it's a little outdated in that sense.

Dr. Sadowski: 11:39

And then also when it comes to systematic reviews and meta-analyses, we I mean we have a very clear gold standard in the methods of how to do it through Cochrane. There's no reason to do any sort of other methodological way that's not already outlined in Cochrane. Cochrane is the standard for it. So they have a free-to-use handbook. Just follow that and it's all been updated. So if you're having something that's being published after all of these things have been well established and you're choosing not to do those, you kind of have to question what's going on.

Dr. Goldenberg: 12:19

Yeah, totally agree. I mean we're on third generation risk of bias tool. These days they get a little bit of a pass because the latest one maybe it came out after this paper was published, but certainly in 2021, they should be using the risk of bias 1.0 tool, not the Haddad scale or Jaddad scale. Yeah, totally agree. I think that's a red flag.

Dr. Sadowski: 12:41

When I published my meta-analysis when I was still a student. Totally agree, I think that's red flag when I published my meta-analysis when I was still a student um I you I used the risk of bias 2.0. Oh, really nice, I didn't. I didn't use it. Yeah, nice, that's awesome. Yeah, I didn't use the, the, the, the original one.

Dr. Goldenberg: 12:56

I used, like the brand, the brand new one yeah, I can't remember when it came out and maybe it was available in 21. Um, yeah, so regardless, like, yeah, like you said, like it's not difficult to do, we have clear guidance on this stuff. We're in third generation now. Why are we using hazard? If it was in the 90/s that would be one thing. 

Dr. Sadowski: 13:12

I graduated in 2020.

Dr. Goldenberg:

So oh okay, so it was available then um, yeah, it was available by at least, I want to say, 2019 okay, there you go.

Dr. Goldenberg: 13:25

So, uh, yeah, they should be on generation three, not one. Um, also, it's not clear that they did the risk of bias assessment in duplicate.

Dr. Sadowski: 13:33

I think they said they did screening no, they didn't mention any of that, really, or the search criteria.

Dr. Goldenberg: 13:38

At least I didn't see it yeah, I think maybe the title and abstract was done independently in a duplicate I I think extraction was not and I think quality assessment was not, and technically all of these things should be done independently and in duplicate. They're not necessarily critical flaws like the other ones, but those are more issues. I agree with you on the outcomes. I thought the outcomes were fine. They made sense to me too. Of course, we can't check what they said a priori they cared about because they didn't register their protocol, and I think that's it for me on that.

Introducer: 14:14

Look, the thing is we don't do this for money. This is pro bono and, quite honestly, the mothership kind of ekes it out every month or so, right? So we do this because we care about this, we think it's important, we think that integrating evidence-based medicine and integrative medicine is essential and there just aren't other resources out there. The moment we find something that does it better, we'll probably drop it. We're busy folks, but right now this is what's out there. Unfortunately, that's it, and so we're going to keep on fighting that good fight and if you believe in that, if you believe in intellectual honesty in the profession and integrative medicine and being an integrative provider and bringing that into the integrative space.

Introducer: 14:55

Please help us, and you can help us by becoming a member on Dr Journal Club. If you're in need of continuing education credits, take our NANSEAC approved courses. We have ethics courses, pharmacy courses, general courses. Interact with us on social media, listen to the podcast, rate our podcast, tell your friends. These are all ways that you can sort of help support the cause.

Dr. Goldenberg:
Should we jump into the results?

Dr. Sadowski: 15:19

Let's go into the results, but I do think we need to address a couple things or maybe we want to wait on this with what Dr Yarnell had some concerns by with regards to the studies that were included.

Dr. Goldenberg: 15:30

Yeah, let's do that. Yeah, so let's jump in. So to that point, they had 93 hits from their search of like five databases, which I think in and of itself is a red flag, like how crummy is your search, that you're searching five databases and you have 93 citations. Like, just to give you a sense, we're doing a study now, systematic review now, of just three databases. We had like 20,000 citations.

Dr. Sadowski: 15:57

Now, that's excessive of and just three databases. We had like 20,000 citations. Now that's excessive. What's now hold on? What's your, what's the question that you're looking into with your, with that systematic review?

Dr. Goldenberg: 16:04

The monster one is prevalence of epilepsy after concussion. And so you know, if you're saying, well, like you know, there's just not going to be a lot of things that pop up when you search for ginger, migraine and randomized control trial, I mean, maybe that's true, but 93, I mean I don't know, I just think that's and there's no like rule like it has to be more than this number, but that just feels like there wasn't a sensitive enough search, especially across five databases. That was their total right like. So I'm wondering if they had overly strict randomized control trial filters. Right, like the filters in these databases are notoriously poor.

Dr. Goldenberg: 16:47

Right. Like you use them when you're a clinician looking for a study quickly, but you don't use them when you're designing a search Like you'll miss a lot of randomized control trials and again, we can't check because they don't publish what their search strategy was. So it's just kind of like yeah, I really doubt it's possible that there's only three randomized control trials in the world on this and they got them all. But I I'm really uncertain from the way they designed their search and executed it. But they found three. So let's, let's talk about those. So, unlike you said, there was some concerns with them. You want to walk through those trials.

Dr. Sadowski: 17:43

And there's an issue with that, because there is some evidence to suggest that feverfew can provide benefit for migraines and there is actually one product that contains feverfew that, as a clinician, I am at least discussing with patients of whether or not they want to consider it. So you don't necessarily know if it's from the ginger or if it's from the feverfew that's providing the benefit. So you know, now you're kind of really down to only two studies of looking at of the effects of ginger on or for migraines compared to placebo. And then one study appeared to be more of a prevention rather than a treatment, which is a different sort of clinical question, and they did not specify if this was a prevention or if this was a meta-analysis, looking at ginger for prevention or ginger for treatment. But if we're looking at their primary outcomes, it looks like it's ginger for acute treatment of migraines rather than prevention of migraines. Mm, hmm, mm, hmm, so like. So that would just really lead me down to to one study.

Dr. Goldenberg: 18:47

Yeah, yeah, totally, totally agree. And then I think also, one of them was a did Eric say is a homeopathic, even like it's not necessarily even herbal level dosing, um, you know, mechanism there, um, it just seems like these three were very disparate, probably should not have been combined, um, from what I'm hearing here, uh, yeah, so that's. I think those are initial concerns. Did they get everything? And the ones that they got just seem quite disparate. Is it appropriate to pool? I think would be the first question.

Dr. Goldenberg: 19:20

Now, one of the frustrating things is that I was surprised when Eric was saying stuff like oh, this one's homeopathic, because I was like I don't remember reading that in the paper or seeing that in a table, and I think he must have actually looked up the studies, which is awesome. Good on him. But that speaks to the poor level of this paper. Like they need to do a better job describing the interventions, especially if we have all these concerns about why they are pooled. You need to be putting enough information about the primary literature in there that the reader can assess for themselves if it's makes sense to be pooling these studies.

Dr. Sadowski: 19:56

So I think that's yet another if it makes sense to be pooling these studies. So I think that's yet another issue here and although you know you and I are kind of biased towards you know our affinity towards systematic reviews and meta-analyses, it's also still important and good on Dr. Yarnell for recognizing that a systematic review and meta-analysis is only as good as the studies in which it includes, right yeah, as well as sort of you know, in addition to the methods of the actual systematic review and meta-analysis itself.

Dr. Sadowski: 20:27

However, if you're just kind of blindly going by someone saying, oh, a meta-analysis showed this or here's what the results show, you know you can really kind of find yourself in a pickle if you don't actually like go down and like really seriously consider, like what, what the trials consisted of, and in kind of looking at those individual studies. And it's also why Cochrane is such a stalwart in this is because if you actually ever read a Cochrane systematic review with metaysis, they actually, you know, include the individual studies at the end. And it's why there are these like 300 page meta-analyses is because after the main component of it, they then actually break it down by study that was included, looking at what population was studied, the intervention. They go a little bit more into detail about it, giving you a quick summary of each individual study so you can then kind of say, okay, was, is the overall effect actually true or is there? Are there concerns, such as concerns with this study?

Dr. Goldenberg: 21:28

Yeah, no, that's. I think that's exactly exactly right, and especially these days where you can publish, you know hundreds of pages of additional material as a supplement online with no additional cost and the journals don't care. I feel like you know hundreds of pages of additional material as a supplement online with no additional cost and the journals don't care. I feel like you know. Not including basic information about a study where you have to track them down yourself to make sense of it really is not excusable these days at all. All right, let's, let's jump into the results. Let's see. Okay, so we've got primary outcome pain free at two hours and pain scores at two hours. Okay, so they say they use random effects model. That's fine. Control group migraine patients. So the ginger treatment significantly improved pain free at two hours and the relative risk there is 1.79. So that's pretty good 80% improvement and the confidence interval is 0.14 to 3.09. So 1.04.

Dr. Sadowski: 22:31

So 1.04.

Dr. Goldenberg: 22:37

I'm sorry, 1.04 to 3.09. So getting pretty close to that one where it would no longer be statistically significant but just kind of makes it just passes. But to that point, while it's statistically significant, the lower bound of that conference interval includes essentially no difference between the ginger and the control, and so that you just kind of need to bear that in mind. Now, to be fair, the upper bound is three times the benefit. So, but that's just kind of get a sense of the imprecision around that estimate.

Dr. Sadowski: 23:07

Yeah, yeah. So it's leaning towards. The noise is going towards favored through ginger.

Dr. Goldenberg: 23:17

Right, yeah, it seems like ginger works for pain free at two hours. That's what it seems like. Yeah, if, if it's okay to combine.

Dr. Sadowski: 23:24

The way I'm interpreting this too as well, is that it says it's favoring the control in figure two, which would seem like it's favoring that the control has more pain freedom, if you will, at two hours. But I think you have to interpret this as there's a 79% risk increase in the control for pain. Conversely, you can kind of view it as there's then a reduction in the pain at two hours with ginger.

Dr. Goldenberg: 24:00

So you're being more generous. So so that was one of the questions that Eric had. Like. If you look at figure two, it looks like the benefit is actually right, like you said, favoring the control, and so you could read it like the way they lined it up. But I think what actually happened because, because the the outcome is the number of people paying free at two hours, right, so a larger number should be better. And it is a larger number, so it should be better. So why is that saying favors control? In the legend? They used RevMan. So this is just like insider tip. They used RevMan software.

Dr. Goldenberg: 24:33

You can tell from the output here there is a little toggle you have to press to flip the, the legend from having favor control on one side versus the other. I think they just forgot to click it because all the other ones have the favor control, um, in the, you know in the right direction or whatever, and I think that's what it is. And in the text they say it correctly, but in the figure it's wrong and I I think that's just because they literally forgot to, and then again, the editor should have caught this. They forgot to flip it, so I think that should be on the right of that graph there favors experimental, which is yeah, you've got about a 80% increased chance of being pain free at two hours if you take it versus the placebo or the control. Okay, yeah, so I think that's what's going on there. I think that was just an error On its own. I wouldn't read too much into that, but what we're seeing is like a bunch of critical flaws and then you know little things piling up on each other as far as like tiny errors. That just tells me, like that these authors were not very careful, and so I think that's concerning as well. Um, oh, also they didn't do a great assessment. That was another thing that they didn't do in the methods, which, again, they should.

Dr. Goldenberg: 25:44

I find it hilarious that at the beginning they say stuff like we follow cochran guidance and prisma guidelines first of all, prisma is not a guideline as a reporting standard, but but then they like actually don't at all do like half of the things that are critically important that these guidelines specifically say that they should be doing Right, okay, so what else did we want to say? So we talked about that outcome. So they are finding a statistically significant I would say clinically relevant improvement in being pain free at two hours. There was no statistical heterogeneity. And then the other outcome reduced pain scores at two hours. They saw an improvement of mean difference of 1.27. You said that was a four-point scale. Did I hear you right on that one? Yep, okay, so this is a pretty large effect. Then If it's a four-point scale and you're dropping it 1.27, that feels clinically relevant. That was also statistically significant but go ahead.

Dr. Sadowski: 26:41

But we do have some methodological things that we have to be uh, considerate of the, the confidence intervals. When, uh, at the very end, when everything is, is, is total, totaled, um, the confidence interval is relatively narrow. Um, you know, if we were to put a grade on this, I think it would be sort of very low to low confidence in that estimate.

Dr. Goldenberg: 27:06

Yeah, I think that's probably true. They don't do grade, which is an issue. But yeah, I think that would probably be fair. I'm just looking at it now. Are you looking at figure three, the mean difference there?

Dr. Sadowski: 27:17

Figure three.

Dr. Goldenberg: 27:17

Yeah, Figure three yeah, so we've got two studies, essentially another. Oh. So here's the other thing. If you look at these two studies right, one of them is weighted 99.4%.

Dr. Sadowski: 27:30

Exactly yeah.

Dr. Goldenberg: 27:32

So it's a quote unquote meta-analysis, which maybe that's even suspect, but actually it's not even a meta-analysis. The result is essentially the result of one study. 99.4% of the information is driven by that one study. So that's like huh, that's kind of curious. And so you know, a reader would say, oh my gosh, like that is obviously overweighted. Let's look specifically at that study and see if that study is trustworthy, is relevant to my research question, et cetera. So that's the Martin's 2019 paper.

Dr. Sadowski: 28:07

And that one also carried 84% of the weight for the other. Primary outcome pain-free at two hours.

Dr. Goldenberg: 28:14

Okay. So basically, all of these results are being driven by a single study, and I'm looking at this one now. This is ginger and this is acute migraine treatment. Okay, so if people were interested in these results, you would have to track down that one study and really make sure that you believe those results, because that is driving the vast majority of what we're talking about here in the meta analysis. Okay, good, that's another good point. What else did we want to talk about? Okay, then we can talk about adverse reactions.

Dr. Sadowski: 28:44

Yeah, let's talk about adverse reactions, okay. Okay, then we can talk about adverse reactions.

Dr. Goldenberg: 28:46

Yeah, let's talk about adverse reactions. Okay, get us started.

Dr. Sadowski: 28:49

Go ahead. That was figure six, so all the way at the bottom, mm-hmm. And yeah, it shows that there was no significant difference compared to placebo.

Dr. Goldenberg: 29:03

Okay. So what's the issue with making a statement like that, based on three small randomized control trials?

Dr. Sadowski: 29:12

Exactly, that is three small randomized control trials.

Dr. Goldenberg: 29:17

I kind of led the witness there.

Dr. Sadowski: 29:18

Yeah.

Dr. Goldenberg: 29:19

Yeah. So randomized control trials are, in general, underpowered to measure important but rare adverse events, right? So for like they're designed, to measure efficacy, right? Usually you need massive observational studies or post-marketing surveillance to capture these adverse events that could be very important. Just you know, one in a thousand or something like that. So you really need to be careful about, you know, making too strong a statement of there was no, there were no adverse events associated, just because it's not a statistically significant difference. This is underpowered and you would run into issues of basically saying, oh yeah, it's safe, right? Well, that's not necessarily the case at all. What else? I think Eric had a question about the p-value on this one too, right? 

Dr. Sadowski: 30:09

Basically, the concern there was you know, if there's no adverse effects of ginger versus placebo with a p-value of 0.05 like, is it actually kosher to to say that if there's a difference or not?

Dr. Goldenberg: 30:20

Yeah, so, um, yeah, so I think that's true. And then I do think maybe, Eric, there there's misreading the Forrest plot, which is totally fair, everybody does. It's poorly written. So you're seeing the p-value on the heterogeneity marker, not the p-value on the overall effect. So I think Eric was wondering well, if the p-value is 0.05, like yeah, technically not statistically significant, but it seems pretty darn close, that's actually on the heterogeneity. So they're basically saying like actually there's pretty close to statistically significant heterogeneity here and if you eyeball that, that forest plot, it makes sense. One of the studies looks completely different than the other two, but the p value on the test for overall effect is what you would say about the is. Are there adverse events? And that's 0.44. But yeah, to Adam's larger point and, I think, to Eric's larger point, you can't oversell adverse events based on meta-analyzing three small randomized control trials. You just always need to be very cautious about that. Okay cool, what else do we have? Okay cool, what else do we have?

Dr. Sadowski: 31:28

Honestly, I think that that's really it. I mean, it was a really it was a poorly done meta-analysis. There's not enough studies. There's really only one that you can kind of take information from. You need more data to answer this question truthfully, and that's just kind of the reality of it.

Dr. Goldenberg: 31:56

Yep, yep, I would agree. I would say the quality of the systematic review itself is critically low, based on formal objective Amstrad 2 criteria. The quality of the evidence supporting benefit of Ginger, like you were guesstimating earlier, grade level probably low or very low. I think you're probably right, probably low just because we're dealing with randomized controlled trials. But yeah, low or very low, I would probably agree. So we've got low level evidence from a really crummy study. I don't, I would not put too much weight on this one at all, and let's just make sure we answered all of Eric's questions, I think. So I want to make sure he's not going crazy. Is indeed this meta analysis pure garbage? Yeah, I would say it's pure garbage, objectively so, and I think we addressed all the other specific questions.

Dr. Sadowski: 32:39

As they say, one person's trash is another person's treasure.

Dr. Goldenberg: 32:43

Who says that and who's treasure? The ginger industry is all big ginger, ladies and gentlemen.

Dr. Sadowski: 32:50

Probably.

Dr. Goldenberg: 32:50

Yeah, they've got their rhizomes everywhere.

Dr. Sadowski: 32:55

This podcast is brought to you by ginger chews.

Dr. Goldenberg: 32:58

Yeah, that's right, not anymore, you know. The other thing is I wrote on my notes on this. I was like, is there really no other systematic review? And I did try to look around and I didn't find anything. I did find some systematic reviews where they mentioned ginger and migraines as like a secondary outcome. They didn't meta-analyze it. So I think this is at least novel in attempting to do that, but I don't think they did it very well. And, eric, if you feel otherwise, or you know of other studies, since you are in the herbal medicine space, yeah, I'd be, I'd be curious, I'm, I would just be shocked if they captured every randomized trial based on how poor that search looked to me. But maybe you're, you know the space and you're like yeah, yeah, as far as we know, there's really only these, these three trials. Cool, all right, anything to add last minute into your name? Co-host.

Dr. Sadowski: 33:49

No, that's it. Everybody get a subscription to Dr Journal Club.

Dr. Goldenberg: 33:54

That's right, and if you have questions like Eric, go ahead and just send us a note formerly info at, or josh at drjournalclubcom, drjournalclubcom. Or if you know us, you can just text us and email us, like Eric and Alana and so many of our other wonderful listeners who have sent in specific studies they wanted us to review. And until next time, this is Josh and Adam signing off. If you enjoy this podcast, chances are that one of your colleagues and friends probably would as well. Please do us a favor and let them know about the podcast. And if you have a little bit of extra time, even just a few seconds, if you could rate us and review us on Apple Podcast or any other distributor, it would be greatly appreciated. It would mean a lot to us and help get the word out to other people that would really enjoy our content. Thank you, hey y'all. This is Josh.

Introducer: 34:48

You know we talked about some really interesting stuff today. I think one of the things we're going to do that's relevant. There is a course we have on Dr Journal Club called the EBM Boot Camp. That's really meant for clinicians to sort of help them understand how to critically evaluate the literature etc. Etc. Some of the things that we've been talking about today. Go ahead and check out the show notes link. We're going to link to it directly. I think it might be of interest. Don't forget to follow us on social and interact with us on social media at Dr Journal Club. Dr Journal Club on Twitter, we're on Facebook, we're on LinkedIn, etc. Etc. So please reach out to us. We always love to talk to our fans and our listeners. If you have any specific questions you'd like to ask us about research, evidence, being a clinician, etc. Don't hesitate to ask. And then, of course, if you have any topics that you'd like us to cover on the pod, please let us know as well.

Introducer: 35:40

Thank you for listening to the Doctor Journal Club podcast the show that goes under the hood of evidence-based integrative medicine. The show that goes under the hood of evidence-based integrative medicine. We review recent research articles, interview evidence-based medicine thought leaders and discuss the challenges and opportunities of integrating evidence-based and integrative medicine. Be sure to visit www.drjournalclub.com to learn more.