St John’s Wort – The Perfect Antidepressant, If You’re German

By Neuroskeptic | July 31, 2009 1:00 pm

The herb St John’s Wort is as effective as antidepressants while having milder side effects, according to a recent Cochrane review, St John’s wort for major depression.

Professor Edzard Ernst, a well-known enemy of complementary and alternative medicine, wrote a favorable review of this study in which he comments that given the questions around the safety and effectiveness of antidepressants, it is a mystery why St John’s Wort is not used more widely.

When Edzard Ernst says a herb works, you should take notice. But is St John’s Wort (Hypericum perforatum) really the perfect antidepressant? Curiously, it seems to depend whether you’re German or not.

The Cochrane review included 29 randomized, double-blind trials with a total of 5500 patients. The authors only included trials where all patients met DSM-IV or ICD-10 criteria for “major depression”. 18 trials compared St John’s Wort extract to placebo pills, and 19 compared it conventional antidepressants. (Some trials did both).

The analysis concluded that overall, St John’s Wort was significantly more effective than placebo. The magnitude of the benefit was similar to that seen with conventional antidepressants in other trials (around 3 HAMD points). However, this was only true when studies from German-speaking countries were examined.

Out of the 11 Germanic trials, 8 found that St John’s Wort was significantly better than placebo and the other 3 were all very close. None of the 8 non-Germanic trials found it to be effective and only one was close.


Edzard Ernst, by the way, is German. So were the authors of this review. I’m not.

The picture was a bit more clear when St John’s Wort was directly compared to conventional antidepressants: it was almost exactly as effective. It was only significantly worse in one small study. This was true in both Germanic and non-Germanic studies, and was true when either older tricyclics or newer SSRIs were considered.

Perhaps the most convincing result was that St John’s Wort was well tolerated. Patients did not drop out of the trials because of side-effects any more often than when they were taking placebo (OR=0.92), and were much less likely to drop out versus patients given antidepressants (OR=0.41). Reported side effects were also very few.  (It can be dangerous when combined with certain antidepressants and other medications however.)

So, what does this mean? If you look at it optimistically, it’s wonderful news. St John’s Wort, a natural plant product, is as good as any antidepressant against depression, and has much fewer side effects, maybe no side effects at all. It should be the first-line treatment for depression, especially because it’s cheap (no patents).

But from another perspective this review raises more questions than answers. Why did St John’s Wort perform so differently in German vs. non-German studies? The authors admit that:

Our finding that studies from German-speaking countries yielded more favourable results than trials performed elsewhere is difficult to interpret. … However, the consistency and extent of the observed association suggest that there are important differences in trials performed in different countries.

The obvious, cynical explanation is that there are lots of German trials finding that St John’s Wort didn’t work, but they haven’t been published because St John’s Wort is very popular in German-speaking countries and people don’t want to hear bad news about it. The authors downplay the possibility of such publication bias:

We cannot rule out, but doubt, that selective publication of overoptimistic results in small trials strongly influences our findings.

But we really have no way of knowing.

The more interesting explanation is that St John’s Wort really does work better in German trials because German investigators tend to recruit the kind of patients who respond well to St John’s Wort. The present review found that trials including patients with “more severe” depression found slightly less benefit of St John’s Wort vs placebo, which is the opposite of what is usually seen in antidepressant trials, where severity correlates with response. The authors also note that it’s been suggested that so-called “atypical depression” symptoms – like eating too much, sleeping a lot, and anxiety – respond especially well to St John’s Wort.

So it could be that for some patients St John’s Wort works well, but until studies examine this in detail, we won’t know. One thing, however, is certain – the evidence in favor of Hypericum is strong enough to warrant more scientific interest than it currently gets. In most English-speaking psychopharmacology circles, it’s regarded as a flaky curiosity.

The case of St John’s Wort also highlights the weaknesses of our current diagnostic systems for depression. According to DSM-IV someone who feels miserable, cries a lot and comfort-eats icecream has the same disorder – “major depression” – as someone who is unable to eat or sleep with severe melancholic symptoms. The concept is so broad as to encompass a huge range of problems, and doctors in different cultures may apply the word “depression” very differently.

[BPSDB]

ResearchBlogging.orgErnst, E. (2009). Review: St John’s wort superior to placebo and similar to antidepressants for major depression but with fewer side effects Evidence-Based Mental Health, 12 (3), 78-78 DOI: 10.1136/ebmh.12.3.78

Klaus Linde, Michael M Berner, Levente Kriston (2008). St John’s wort for major depression Cochrane Database of Systematic Reviews (4)

  • http://www.blogger.com/profile/06832177812057826894 pj

    “In most English-speaking psychopharmacology circles, it's regarded as a flaky curiosity.”

    That's a bit unfair. It is generally avoided because it is not generally pharmaceutical grade (so dosing is variable), has a lot of drug interactions, and is less well studied compared to other antidepressant medications.

    But that is an interesting question about Germany. I've found in other studies of semi-herbal drugs that German studies seem more likely to find a positive result. And, of course, we all know about Chinese studies.

  • http://www.blogger.com/profile/09598085988718342314 carl

    Yet another possibility is that Germans tend to have genetics favorable to SJW response…

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    pj – OK it's a bit unfair. But I think it's safe to say that if someone developed a drug which was a) side-effect free and b) better in mild than severe depression, unlike every other drug, it would get more academic and clinical attention than St John's Wort.

  • Anonymous

    Might be also because in most german speaking countries you can buy St John's Wort in the green grocery section….

  • http://www.blogger.com/profile/06832177812057826894 pj

    Hmm – I'd love to write a post on the Cochrane review but I don't have the time (on-call).

    The evidence is marginal that SJW was any better in mild versus severe depression and there is also marginal evidence that there is a severity gradient in comparison to antidepressants (which you'd think would be most marked since the latter are supposed to show the opposite pattern).

    I'm unhappy at lack of sensitivity analyses – not sure why they bothered doing all those trial quality scores (worth someone looking at this). This is one of the areas where trial dodginess can manifest and is particularly important for concluding that there was no difference between SJW and antidepressants.

    The side-effects analyses could really have benefited from some more detail – and, in particular, I am very sceptical that SJW has no more side effects than placebo despite being supposed to act via a similar mechanism to other antidepressants, and, of course, it can cause serotonin syndrome – again a sensivity analyses would be helpful here.

    Their conclusion that there is no publication bias because no manufacturer told them of any negative trials was…dubious at best…particularly as they actually documented evidence of publication bias (abstracts vs. papers, unpublished negative trials). Compare this with Kirsch who at least had a good idea they had all trials, and who found a similar effect size overall (if you analyse the data right – something like 2.7 for antidepressants over placebo vs. the 3 HAMD points for SJW over placebo in this study).

    I personally have a reluctance to use a drug that screws around with other drugs including the OCP and a general scepticism about the quality of the data (e.g. Germans get 3 more HAMD points benefit than others? Really? Yeah, right).

    On the other hand, many people like herbal medicines and it might be a useful alternative to SSRIs in a certain cultural subgroup – I'd be very reluctant to go around recommending it in mild depression mind you (would have been nice for them to have at least indicated some rough HAMD baseline severities a la Kirsch and what they mean to help clinicians!).

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    I'm probably going to write some more about this meta because it is pretty interesting -

    Some random thoughts:

    * They don't seem to have presented an analysis in terms of publication year or sample size – they did compare the top 50% to the bottom 50% in terms of precision and found that the more precise trials found smaller effects. They should also have looked at trial quality although they comment that it was in general high.

    * If SJW works as a monoamine reuptake inhibitor then I will disbelieve any claim that it does not cause typical monoamine reuptake inhibitor side effects. But it might not work in that way… we don't know.

    * The evidence that it works better in “mild” vs “severe” depression is indeed weak, but, bear in mind that you would expect strong evidence for the exact opposite, if this were an SSRI.

  • http://www.blogger.com/profile/11663852607629403279 Gina Pera

    Interesting story. Thank you. I just discovered your blog after reading your excellent column on anti-medication non-trolls at PsychCentral. After having a barrage of their missiles launched at me lately, I Googled “anti-medication trolls” and found your piece.

    They are a rough crowd, and I sure hate ceding the Internet to them. But, unfortunately, they have a lot of time on their hands…..

    Back to this topic, the trouble with St. John's Wort is the same trouble we have with any herbal or pharmaceutical: If the diagnosis is incorrect, you risk increasing symptoms instead of mitigating them.

    For example, ADHD is often misdiagnosed as depression or anxiety by less-than-astute clinicians. That means these patients are often give SSRIs, which decrease activity in the prefrontal cortex (which is already suffering from decreased activity). And it's the same with St. John's Wort.

    Of course, with late-diagnosis ADHD, depression and anxiety are highly co-morbid. So, the depression and anxiety must be addressed, but in addition to the ADHD.

    I look forward to reading more of your blog.

    Gina Pera, author
    Is It You, Me, or Adult A.D.D.?

  • http://www.blogger.com/profile/11663852607629403279 Gina Pera

    Correction: So sorry….I found this blog through that PsychCentral piece's writer: Sandra Kiume. Her blogger profile lists this as a favorite blog.

    My brain is a little scrambled this morning. Funny how dealing with about 15 unfounded attacks on my character on a Sunday morning does that. ;-)

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    Hi Gina,

    Thanks for the correction – for 10 seconds there I was worried that PsychCentral were stealing my stuff! (They've never done that, but other sites have.)

    Re: ADHD, that's true, diagnosis is certainly important, although always hard. With SSRI antidepressants, though, I think there's a strong perception amongst doctors that they are useful for a wide range of conditions and can be safely tried “because it can't do any harm”. So they get prescribed for many reasons other than depression – all sorts of anxiety disorders, in particular, “conduct disorders”, you name it. They're the aspirins of psychiatry.

  • http://www.blogger.com/profile/08617490362195568500 Gina Pera

    So true, Neuroskeptic.

    Many years before I became an Accidental Advocate for ADHD Awareness, I anticipated fallout from the one-size fits all SSRI marketing campaign to family doctors and gps. I didn't quite know what would happen but knew it wouldn't be good. (Journalists often have an instinct for such things.)

    Years later, I've become too educated on why this is such a dangerous practice. And, it's really not good for my mental health. ;-) Neither is learning how, well, intellectually impaired many physicians are. We just can't blame Big Pharma for all the fallout.

  • http://www.mens-hormonal-health.com/list-of-antidepressants.html Brian Hildebrandt

    I've been on St. John's Wort and wasn't entirely impressed although I can see it helping people with mild depression perhaps.

    It's too bad we can't see more studies since it's not a patented product.

  • Anonymous

    Gina, I am on those folks you have probably labeled as an anti-medication troll. LOL by the way at your description.

    Anyway, I agree with you about doctors being clueless about how to prescribe these meds. So now what is my label since I agree with you about something?

    By the way, I know someone whose psychiatrist saved this person's life in recovering from insomnia with very very careful prescribing of low dose meds. Not the usual throw everything at the kitchen sink routine and let's see what sticks. So again, do I still qualify for membership in the troll club:)?

    People like you could learn from us trolls, particularly the ones like me who have learned how to taper slowly off of psych meds without the help of a psychiatrist. Knowing how to customize our doses could help the folks who do find psych meds helpful but can't seem to find the right dose for their body. It is either too low or too high.

    Sorry for getting off topic but I couldn't resist responding on that point. Regarding St. Johns Wort, actually, I feel it was the most effective antidepressant I took during my 10 plus years of taking drugs. The therapist I saw at the time agreed.

    The quality makes a difference but unfortunately, the only research I found at the time was a 98 LA Times article. Believe it or not, they rated the Safeway grocery store brand as being high and that certainly proved true in my case.

    AA

  • Anonymous

    I think the quality of St. John's wort differs a lot. Germans are ahead of us. My friend is using Cesradyston *german kind) and she is Very happy with the results. The problem is this drug is kind of expensive there, so I send her several brand of St.John's Wort from U.S. And they don't work the same way Cesradyston does!!!

  • http://www.blogger.com/profile/18183750941203308731 Steve

    o.k., I'm an attorney, not in the medical field, so take this for what it's worth. I'm also half German with my father being first generation American, and if there's a personality trait I would say is common place among Germans, it would be the tendency to be somewhat “high strung” to say the least (including myself) … could it be that St. John's Wort works well with depression combined with Anxiety? Have any studies been done on this point?

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    Steve – I don't think there have been any studies looking at that directly, but in this study they did find that milder depression – which is often associated with anxiety – responded slightly better than more severe depression. So it's quite possible…

  • Anonymous

    Here's the thing. I'm a mental health professional – Senior Practitioner, if you must know – and I started using SJW in march of this year to see if it could help with a nasty free-floating anxiety that kicks in, as regular as clockwork, early evening. This is accompanied by intrusive thoughts of death and mortality, and I seem to have no control over them whatsoever. And a crap sleep pattern.

    The result has been remarkable. Yes, I get occasionally troubled but no more so than one would expect, bearing that we're all going to do and I am not getting any younger. Overall, sleep is a million times better and so is my mood and thought-processes in general.

    You do have to watch what your eating, though. I was warned that SJW works in an MAOI-type way and you have to be careful of the usual tyramine-heavy suspects. I didn't, and got rewarded with a monster headache.

    In short, therefore: it worked for me.

  • http://www.depressionmood.net/ depression mood

    Signs and symptoms of depression

    Depression varies from person to person, but there are some common signs and symptoms. It’s important to remember that these symptoms can be part of life’s normal lows. But the more symptoms you have, the stronger they are, and the longer they’ve lasted—the more likely it is that you’re dealing with depression. When these symptoms are overwhelming and disabling, that's when it's time to seek help.

  • http://www.blogger.com/profile/10185516412214000909 Tilidh

    I have used St. John's Wort in the past with good results, but it took about 8 weeks before I really noticed the beneficial effects. I was using a particular brand that was used in the German tests. Any brands I tried that were made in North America did not work for me.

    Obviously the trials would be different if different formulas were used. I'd like to hear more about that because it could certainly account for significant differences.

  • Alfred

    You should look seriously at the origin and quality of the herb. These products are notoriously variable. Perhaps the Germans have better quality – as always.

  • Anonymous

    “The obvious, cynical explanation is that there are lots of German trials finding that St John's Wort didn't work, but they haven't been published because St John's Wort is very popular in German-speaking countries and people don't want to hear bad news about it.”

    I would say that's more delusional than cynical. It makes zero logical sense. If St John's wort is a patentless, cheap, and easily avalible herb then who is the 'powerfull lobby' who is manipulating the publications in journals? Scientific studies are published in journals, they do not cease to exist because the public doesn't want to believe in them. So, appealing to the beliefs of the german general public is a non-sensical explanation for why the publications in german journals reach differernt results. Manipulation of the studies would require manipulation of the journals and that requires a strongly intrenced industry interest with lots of money to spend. A herb you can grow in your back garden is not likely to be the basis of an intrenced industry interest.

    Infinetly more likely is the opposite case; that studies in english speaking countries are delibrately falsifed to make st John's wort look ineffective. Because the existence of a cheap, patenless, unmonoplisable alternative that people could grow in their back garden could not be tolerated by the pharmacutical industry here as it would their pattents worthless. An industry that makes billions every year out of people's depression.

    • PeculiarMane

      Exactly! Finally someone said it!
      I came here through a google search for St John’s wort. I started taking it again after it made me feel better a few years ago.

      Considering the favorable reviews by scientifically conducted trials (even the ones conducted in English speaking countriesare positive damnit! Can’t people read?) it is INSANE that doctors will not invite you to try it first before meds like Effexor which, if they do work (and it’s a big “if”) are a hellish nightmare to get off of.

  • Optimist

    I am curious about SJW. I have never tried antidepressants before. My PC doc prescribed Paxil for me a week ago. After doing some research I told her I didn't want to take it due to the horrible withdrawal effects I read about. I had read that Prozac was easier to get off of so I told her I would try Prozac. I went to the drug store to pick it up a week later after doing more research and the prescription had not been sent in. So I looked for SJH and bought it. In all my research SJH kept coming up so I thought maybe I should give it a try. I don't know what to expect and I am wondering if anyone might have some prior experience they wouldn't mind sharing. Thanks so much for your time!!!!

  • Anonymous

    I may be more cynical than most posting on this board, but I believe that US pharmacology circles ignore the efficacy of St. John's Worst precisely BECAUSE it has no patents on it. Where is the profit there? I am sure that there are many caring individuals in hte US pharmaceutical industry who would advocate for low-profit drugs , but who would pay for their research? Germany and much of Europe are far more supportive of natural cures and their research typically takes years to become fully accepted here.

    In my own experience, I have had great success with SJW. I come from a family where manic-depression and major depression is common and I periodically go through periods of very depressed mood. I have been taking SJW periodically over the past few years and find that it helps to slowly uplift the “doom and gloom” feelings and anxiety I get, and after a few weeks (typically 3-4)I feel much better. I generally stay on it for about 8 weeks at a time and discontinue when I don't need it anymore. No withdrawal, no side-effects. Strangely, it even improves my sleep which can be strongly impaired when depressed.

    I'm not saying that it would work as well for everyone – but I take the recommended dosage of SJW produced by a well-known German company (not sure if I can post it here, but it is Nature's W*y). Formulations tend to vary, but I have found this one to be remarkably consistent. I am not a person who believes that all natural remedies are sage or effective, but I would rather take my chances with a time-tested remedy with no chance of addiction than bet the farm on a drug that some profit-minded pharmaceutical company wants to sell me!

  • Wes

    Just thought I'd say SJW worked for me. I had pretty serious depression at the time. I'm talkin', you know, life-threatening thoughts. Every day. Around 3 weeks after starting on SJW, I hadn't paid attention to it, but one day I realized I simply wasn't having those thoughts anymore.

    I'm sure some people will think it's just a coincidence, but if I was in the mood to write more details here about before, after, and since, they would change their opinion.

    I was taking whatever brand was in the dark-green bottle at GNC. To further your German theory, though, I'm not in Germany but am mostly of German descent. :)

  • courtney

    For whatever it's worth: I used St. John's Wort at one point to combat severe depression. Once it began working (after a full 6-7 weeks) I felt an obvious but gentle mood change for the better. It was a more peaceful/natural feeling than say, the SSRI's. I was able to feel more joyful and lighthearted, a subtle shift, but definitely a real one. Oddly enough, it was a Walmart brand that I found to be very effective. I think the reason SJW is not prescribed is that it really does take 2-3 times as long to begin working than an SSRI. 2 months is long time to wait when you are really struggling, and I imagine most people quit before it begins working. My experience is that if you can stick it out, taking it diligently for weeks with no benefits, it is in the end, worth the wait.

  • Anonymous

    I've had a good response to SJW. No doubt about it. I'm rather giggly at times, which is more like my self from 10-15 years ago.

    I did have an obvious and weird hormonal effect from SJW a few months after taking Depo Provera. The Depo was making me bleed constantly, probably because I had fibroids which is due to a hormonal imbalance (estrogen dominance). (Stay with me here.) A week after starting the Depo, I started dropping bloody chunks of myself. It was really intense and didn't let up until I stopped the SJW. Now here's the weird thing. My moods were better on the Depo, and they were better on SJW. Depo is progesterone and is essentially the hormone that makes a woman shed her lining. SJW did the same.

    I'm half-Dutch, so I don't know whether that has any relation to the Germanic tests. But I'd like to speculate that there may be a tendency for hormonal imbalances among German people (or German women).

    Either that or the non-Germanic tests were sabotaged by a money-grubbing pharmaceutical company. :)

  • Anonymous

    I reckon I'm a German who just happened to port over to Australia through osmosis. LMAO.

    This SJW is brilliant. I'm a happy woman again. Giggles

  • Anonymous

    could it be that the German studies are more immune to the pressures of the pharmaceutical industries??!!!
    in the US and England the Medical community are fearful to be black listed by the industry, at the danger of being refused jobs, contracts and grants….

  • http://www.blogger.com/profile/00068671443994496718 Amy

    The German studies use SJW that is standardized for hyperforin content as opposed to hypericin. For myself (full disclosure: my ancestry is 1/4 German), only SJW standardized for hyperforin is effective. The German brands Perika and Kira and the U.S. brand New Chapter are, as far as I know, the only SJW products on the market standardized for hyperforin. New Chapter has at least one product that's standardized for both, but I prefer the German products–the ones with a lot of hypericin tend to keep me up at night. The German studies probably used Perika or Kira. Hyperforin also degrades quickly–the German products are supposedly formulated to have a longer shelf life.
    I expect the difference in results is due to the specific formulation used, not the ethnicity of the study subjects.

  • Dora

    I had been suffering for a couple of years with unbearable anxiety that also caused me depression when I decided to do something about it. I tried everything including HRT (as I was also entering perimenopause) and antidepressants. Both not only did nothing to help but even worse, they caused me horrible side effects. In my desperation I did a bit of research and decided to try St John's Wort. Talked to my GP and she agreed on supervising the trial. During the course of the first week I started to notice that I did not struggle as much with my invasive anxious thoughts. Later on I started to notice an improvement in my mood and more recently I have started to notice the improvement in the way I can handle stress now (I don't feel panicky or sick in the stomach or fainty).Even my sleep has improved as before I was suffering with horrible insomnia.
    I have been taking St. John's Wort for 6 months and I know very well that the marked improvement in my health cannot be my imagination.
    I know everybody is different and even different brands can be more or less effective. It is really a matter of trial and error and to see if it works for you or not.
    I would like to encourage you if you tried everything else without success, you lose nothing by giving it a try. I would suggest try it for no less than two months.
    I will not give you the brand I take because you can think I am trying to promote it, but my only motive is to give some hope to sufferers. I have also found very helpful this website, amongst many others I read before making the decision to try it
    http://www.sjwinfo.org/
    By the way I am not germanic I am from Spanish background.

  • Anonymous

    I'm american. I'm skeptical, because I've tried many drugs that haven't worked. I'm trying it. So I guess I'll find out if it works or not. So far, I've just started. I'm also researching it so that I know what I'm getting into.

    Maybe German's have a more favorable SJW response, or maybe not. I've got German ancestry (answering the above), and mostly that.

    From what I've been reading, the jury is out. A friend said it worked for his mother, who lived with him for a long time. Which is why I'm trying it.

  • Anonymous

    Imagine if every person who needed a drug for depression/ADHD/AUTISM, etc..were actually properly diagnosed with a PET scan to see what was needed instead of spending years being used as a test subject by guessing doctors. Sigh.

    • HF74

      PET scans show absolutely nothing when it comes to anything other than epilepsy and some sever psychotic disorders. If it were that easy we would have all been cured long ago.

  • Anonymous

    The first time I took SJW was when I got it from a German Pharmacy. It worked well. When I got it from an American Pharmacy, I didn't get quite the same results. I got it again from the German Pharmacy and improved. Perhaps, someone is barking up the wrong tree here. There may be inconsistency with the results because of other environmental factors when processing the plant. Would someone mind thinking outside the box here?! I would like to add, I had no idea that there was this contention over test results until today, so I was not biased based upon a preconceived notion when I made this observation.

  • Dr. Med.

    But what about this:

    “The picture was a bit more clear when St John's Wort was directly compared to conventional antidepressants: it was almost exactly as effective. It was only significantly worse in one small study. This was true in both Germanic and non-Germanic studies, and was true when either older tricyclics or newer SSRIs were considered.”

    So, if St. John's Wort is no good, then the other antidepressants are no good either? Maybe we should do a study that examines what companies were involved in sponsoring the trials?

  • HF74

    I have suffered from Depression pretty much my whole life. I am highly resistant to the placebo effect. I have gone through a dozen prescription medications before I can actually feel one work a little. That being said SJW does actually seem to be working for me, it even helped ween me off Venalafaxine(Effexor) which is nasty stuff to get off of. After settling into it for a while I plan on having my wife give me a blind test by refilling a bunch of capsules with a placebo, she will know and record if I am taking the real SJW or the placebo but I wont. I am also going to try melatonin to ween off Quetiapine(Seroquel), more nasty stuff. I am usually a huge skeptic, but I am feeling great right now and plan on proving whether or not it is from the SJW.

  • Vida Cropas

    Could it simply be that big pharma, controls studies, and does not want a natural and cheap product cutting into their market shares? I have used St. John’s Wort for years, with wonderful results…It has taken me from crying and unable to get out of bed -to a normally functioning person. ;)

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About Neuroskeptic

Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.

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