Talk:Berberine

First Paragraph

Is it okay to modify the sentence with the "citation needed" at the end of the first paragraph (re source of Berberine) that has been there since 2011? The Wikipedia links to the shrubs and plants that produce berberine (mentioned in first paragraph) all contain information about the plant parts that are used in traditional herbal medications. All these plants have parts that have been variously used for this purpose, fruits, seeds, bark, roots/rhizomes. However, the cited literature often doesn't make empirical causal associations between berberine and the observed therapeutic effects, but merely hypothesizes that these effects may be due to berberine. The fact is that there are quite a few other bioactive alkaloids produced by the same plants, which may well contribute to the effects of the herbal preparations. Should this be reflected in the first paragraph? Suirauqa (talk) 16:44, 28 December 2015 (UTC)

Is this one of the citations that are required?

Ruchi Badoni Semwal, Deepak Kumar Semwal and Pratibha Kapoor, 2012. Dyeing Properties of Berberis aristata DC with Natural and Synthetic Mordants. Trends in Applied Sciences Research, 7: 392-399.

DOI: 10.3923/tasr.2012.392.399

URL: http://scialert.net/abstract/?doi=tasr.2012.392.399 — Preceding unsigned comment added by 182.239.194.197 (talk) 22:05, 18 June 2017 (UTC)

Effective dosages of berberine

I would like to see information added to this article about effective dosages of berberine. At this moment there there is no info in the article about what dosages are used in research. I would like to relate that information to the berberine content of food supplements containing herbal extracts of goldenseal (Hydrastis canadensis) and/or Berberis vulgaris. itsme (talk) 08:31, 1 September 2009 (UTC)

Please read the articles cited, and you will find that the effective daily dosage is 1 to 1,5 grams. You are welcome to add this info if you so choose. —Preceding unsigned comment added by 88.114.28.94 (talk) 18:53, 11 September 2009 (UTC)

eg. "The therapeutic dosage for most clinical situations is 200 mg orally two to four times daily.[Birdsall TC, Kelly GS. Berberine: Therapeutic potential of an alkaloid found in several medicinal plants. Altern Med Rev 1997;2:94-103.]" Rod57 (talk) 11:52, 6 January 2011 (UTC)

medical status

Clinical use in western medicine only seems to be mentioned in the context of clinical trials for diabetes. Does it have FDA type approvals for any indications ? It seems to be a component of Armolipid Plus. There are 2 trials registered for Polycystic Ovary Syndrome (PCOS) [1]. Rod57 (talk) 04:19, 5 January 2011 (UTC)

Unlike drugs, dietary supplements do not require FDA approval to be marketed. The restriction, however, is that with rare exceptions, the supplement companies are not allowed to make any claims for prevention or treatment of a disease EVEN IF TRUE. There is a difficult path to FDA-approved health claims. Most supplement companies do not try, and instead live with the restriction. David notMD (talk) 17:16, 6 May 2017 (UTC)

Toxicity

Need a section on acute and chronic toxicity (it seems to be fairly poisonous) and the effects of overdosing. Rod57 (talk) 11:02, 6 January 2011 (UTC)

With exceptions, I'm in agreement with Rod57. Berberine is a quaternary ammonium salt. Since other quaternary ammonium cations have proven to be toxic (dose dependently), it could be theorized that Berberine exerts similar effects. While there isn't a consensus, there seems to be spotted agreement on the toxicity of Berberine among those who study it (respective to dosage), but a dearth of available evidence in human studies. One study at NCBI has taken stabs at it with studies in mice, and shown it is in fact toxic to certain cells on them, though another study apparently showed that it wasn't significantly toxic in 'rat' cells. Two NCBI published studies cited here appear to blame some of the plants, roots, and rhizomes Berberine is derived from rather than Berberine itself: http://examine.com/supplements/Berberine/#summary12

There have been some suggestions that Berberine (the ingested form) may be harmful to intestinal flora, and longer term use may damage the lining of the intestines. Anecdotally, I've had a CT scan of my abdomen for what I thought was an unrelated issue, and was found to have Diverticulosis (not full blown Diverticulitis), and had been taking Berberine for a month prior. The gastrointestinal symptoms I was experiencing occurred after starting the supplement. This is only remarkable because a colonoscopy three years ago showed nothing of the kind, and the symptoms appeared within a month of regularly ingesting it. I realize my personal experience isn't by itself suggestive enough to warrant an indictment of ingested forms of Berberine, but it's worth noting, especially in the event any similar cases ae reported. The concerns expressed here http://www.youtube.com/watch?v=WO5c2L8CsDQ and in the warnings here http://www.wellness.com/reference/herb/berberine/dosing-and-safety, may arise from findings on quaternary ammonium found here http://www.inchem.org/documents/pims/chemical/pimg022.htm#SectionTitle:2.1%20%20Main%20risk%20and%20target%20organs , though not necessarily about Berberine in supplemental form. Given its potential use for its medicinal properties being widespread, It's worth investigating. Brian_Soto (talk) 12:29, 26 March 2012 (UTC)

With respect, three years is plenty of time for diverticular disease to develop.171.96.49.49 (talk) 10:00, 23 August 2014 (UTC)

Liver Cancer, Neurotoxicity, and Atherosclerosis risks

I added mention and references to two studies indicating berberine's serious potential to increase the risk of liver cancer, if taken over a lifetime. Most people assume that if a substance can kill cancer cells, it must lower the risk of cancer if taken every day. This is absolutely not the case, however. Many chemo drugs can cause secondary cancers. In fact, a class of chemo drugs called topoisomerase II inhibitors have also been found to cause leukemia, mainly AML (note berberine is a topoisomerase II inhibitor). And these studies re berberine and liver cancer are all the more credible as to the mechanism involved considering that coffee has been shown to dose-dependently lower the risk of human liver cancer, and its constituent chlorogenic acid induces the formation of topoisomerase I- and II-DNA complexes in cells (i.e., coffee works the opposite way from berberine in this respect, and coffee decreases liver cancer risk). In fact, for this same reason, if you consider supplementing with berberine, it would make sense to drink about 6 cups of coffee or decaf coffee a day to try to offset the potential for berberine to promote liver cancer via this mechanism.

I also cited a study showing neurotoxic effects of berberine. There are a couple of additional studies in support of this finding. However, I also cited studies showing neuroprotective effects of berberine. Obviously, the jury is still out on this one.

Lastly, I cited a study showing that berberine can increase the risk of atherosclerosis and foam cell formation, despite its cholesterol lowering effects. The jury is still out on this one, also, as other studies (I cited these, as well) show that berberine decreases the risk of atherosclerosis by mechanisms other than its cholesterol lowering effects.

I am not on some anti-berberine campaign. But I felt it worth noting that this chemical appears to have some concerning effects, in addition to its many beneficial ones. Probably the best way to think of berberine is as a true pharmaceutical drug with powerful beneficial effects on blood sugar and other health measures, but also with some concerning issues in its safety profile that must be taken into consideration and factored into any decision to supplement with it.Bdmwiki (talk) 14:34, 3 April 2015 (UTC)

The Wikipedia article on PCSK9 says that berberine inhibits PCSK9, thereby lowering cholesterol. I am not saying that the risk/benefit analysis therefore favors taking berberine, just that it is an effect of berberine that should be mentioned. Pollira (talk) 03:58, 30 March 2017 (UTC)

References

Damaging edits of this article

This current version has been radically shortened comparing to what it was a year ago, supposedly in the name of reliability. Although SOME claims of the older versions were not solidly doccumented, most of them were. For example, version of October 10, 2015 had 109 references, mostly in reputable journals and books. The present version has only 13 references. Much damage has been done. Just one example, out of tens alike: Reference #18 of the Oct.10, 2015 "The anti-inflammatory potential of berberine in vitro and in vivo. Kuo CL, Chi CW, Liu TY (January 2004) Cancer Lett. 203 (2): 127–137. doi:10.1016/j.canlet.2003.09.002. PMID 14732220." - why did someone remove this reliable and very important information? And tens of other referenced information? Someone careless has deprived the general population of the right to know those very important medical information. — Preceding unsigned comment added by 45.51.77.190 (talk) 01:33, 8 September 2016 (UTC)

See WP:WHYMEDRS. Alexbrn (talk) 05:31, 8 September 2016 (UTC)

It is essay, not guideline Cathry (talk) 09:38, 3 February 2017 (UTC)

And what MEDRS means is that Wikipedia has chosen to be a trailing indicator for what is true. New, and sometimes reversed science is in the journals, Wikipedia waits until the science is at or closer to consensus, based on human evidence. David notMD (talk) 17:19, 6 May 2017 (UTC)

From WP:MEDRS: "This page in a nutshell: Ideal sources for biomedical material include literature reviews or systematic reviews in reliable, third-party, published secondary sources (such as reputable medical journals), recognised standard textbooks by experts in a field, or medical guidelines and position statements from national or international expert bodies." Even if medical consensus isn't established, citing correctly sourced information is the goal (not "what is true"). I agree with the OP, stripping this page of its sourcing was damaging in the long term. The specific example of PMID 14732220 was correctly sourced, was it not? MrSirGuyFriendBuddyOlPal (talk) 15:59, 16 May 2021 (UTC)

It's a primary source, so not WP:MEDRS. Alexbrn (talk) 09:23, 2 November 2021 (UTC)

Chemical nomenclature

I don't think any IUPAC name can be, according to current state, designated ad preferred, since it's a natural compound, that can be named as a derivative of berbine, listed in IUPAC 2013 Blue book. —Mykhal (talk) 09:04, 9 September 2022 (UTC)

Looking at the Blue Book (P-12.1, P-100), it chooses "not to identify" PINs for natural products, noting that no set of recommendations has been produced for choosing systematic vs. semisystematic names for natural products. However, it still seems useful to identify the unique systematic name produced by the rules of P-5 and other restrictions on PINs, to distinguish it from other systematic names. Also, there are no restrictions on how many modifications can be done on natural product parent hydrides: they can be modified ad libitum into many more general parent hydrides, making the whole category of "natural products" with no PINs somewhat vague. Perhaps I have been a fool this whole time; in the meantime, I've added a typical semisystematic name. LegionMammal978 (talk) 06:26, 10 September 2022 (UTC)

.. ​ Additionally current "preferred" one, “9,10-Dimethoxy-5,6-dihydro-2H-7λ⁵-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinolin-7-ylium” is most likely wrong (which would correspond to formal removal of hydride anion from pentavalent nitrogen compound). —Mykhal (talk) 09:33, 9 September 2022 (UTC)

This is in accordance with P-73.3.1.

1. We start with the neutral parent compound, named with fused ring nomenclature as "[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinoline".
2. We use the λ-convention and the suffix 'ylium' to indicate the bonding and charge of the N atom, yielding "7λ⁵-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinolin-7-ylium".
3. We add a single indicated hydrogen between the two O atoms, yielding "2H-7λ⁵-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinolin-7-ylium".
4. We use the 'hydro' prefix to indicate the added hydrogenation, yielding "5,6-dihydro-2H-7λ⁵-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinolin-7-ylium".
5. Finally, we add the two substituents, yielding "9,10-dimethoxy-5,6-dihydro-2H-7λ⁵-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinolin-7-ylium".

I also found the rule confusing at first, but it makes some sense. In its normal state, N is attached to at most 3 other skeletal atoms. Adding a 4th bond would require the 'dehydro' prefix, which is not generally used in PINs; the rules would have to specify the interactions between 'dehydro' and other modifications to hydrogenation. So instead, the Blue Book recommends the creation of a fictional λ⁵ N from which an 'ylium' suffix removes a hydride, so that all 4 skeletal bonds can be attached to it. LegionMammal978 (talk) 06:26, 10 September 2022 (UTC)

Enzyme inhibition

You did a revert claiming "Not WP:MEDRS sources, but you didn't justify exactly why you think they are not WP:MEDRS. These sources are secondary (reviews) that are fully WP:MEDRS compliant, and the described effects have been in fact. Could you please specify why you think that they are not WP:MEDRS? Also, you mentioned WP:CRYSTAL (speculation). Can you please specify why you think it is a speculation? These claims are present in the article cited. Maybe you didn't like the explanation of CYP3A4. Let me remove the explanation. Please review that version. (unsigned by Maxim Masiutin)

Removal of this content was justified because the sources are about primary research and do not represent sufficient clinical evidence for use of berberine in any disease condition. The Pharmazie source does not review advanced clinical trials (there are none) and the Planta Med source states that evidence for effects of berberine is "limited" and "weak", i.e., not worth mentioning in an encyclopedia.

See WP:MEDASSESS - there are 1) no MEDRS reviews of using berberine for treating any disease, 2) no clinical organization recommending its use, and 3) no national regulatory agency approving its use in humans. The sources you added are primary, unfiltered information (left and right pyramids, respectively).

I removed mention of berberine as a traditional medicine because it came from a non-reputable, unusable source describing mouse experiments. Zefr (talk) 01:41, 29 December 2023 (UTC)

My objection was about the following text that you reverted: Berberine inhibits the activity of CYP3A4, an enzyme involved in drug metabolism. I agree that you removed many improper statements, but I do not agree that you removed a statement about CYP3A4 inhibition. It was not me who wrote about "Culture and society" and I agree that you removed it. But the statement about CYP3A4 which I added after resolved your objections each time you reverted 3 times which is against the 3-revert rule. I will ask administrators whether such actions were appropriate. Also, you reverted that without proper explanation on the talk page, and you didn't explain until I created that section. The statement about CYP3A4 was confirmed by two medline-indexed reviews: PMID 34620272, PMID 22855269, which I cited. Therefore, please consider restoring the claim about CYP3A4 inhibition. Maxim Masiutin (talk) 10:44, 29 December 2023 (UTC)

@Bon courage - can you please help us here too? I made a claim that Berberine inhibits the activity of CYP3A4, also backed up by two sources that I found reliable (reviews indexed in MEDLINE). Still, the user Zefr disagreed. I tried various style: first a style that gives more information on what CYP3A4 is, and explains how it was established (on measuring medicine levels in human subjects), then I made a plain simple statement, but we still disagreed. The point of disagreement is the following. I am convienced that it should be mentined that Berberine inhibits the activity of CYP3A4, whereas Zefr considers it should not be mentioned as the sources are not enough to support this claims. Maybe you can help us get into consensus and we would not be needed to ask for a formal resolution process. Thank you again! Maxim Masiutin (talk) 16:36, 29 December 2023 (UTC)

@Bon courage - can you also please help with this one if you have time? Maxim Masiutin (talk) 19:08, 29 December 2023 (UTC)

I don't see any particular problem with the sources, so inclusion will boil down to a question of what is WP:DUE. In general if mentioning lab work I think it is best to be clear by saying laboratory experiments have found, or somesuch. Bon courage (talk) 09:06, 30 December 2023 (UTC)

These where not laboratory experiments. PMID 34620272 mentions several studies which demonstrated that berberine can increase the concentrations of cyclosporine in renal transplant patients and midazolam in healthy adult volunteers, confirming its inhibitory effect on CYP3A4. These were studies on human subjects, measuring levels of plasma cyclosporine and midazolam. Measurements of substances metabolized by an enzyme and taking inhibitor (or inducer) in one group and placebo in another group is a way to confirm that particular substance is an inhibitor (or inducer). Why did you mention laboratory experiments (lab work)? Zefr mentioned that this source "does not review advanced clinical trials (there are none)". However, current state of the art allows even using invitro studies and/or simpler trials (not necessarily advanced clinical trials) to be able to state that a particular substance is an inhibitor/inducer. The second study PMID 22855269 which is an earlier one states that evidence for effects of berberine is "limited" and "weak". Zefr considers such kind of evidence is not worth mentioning in an encyclopedia. Still, the evidence was "limited" and "weak" at the date of publication. Later studies mentioned in PMID 34620272 confirmed the findings described in PMID 22855269. Maxim Masiutin (talk) 09:47, 30 December 2023 (UTC)

I assumed it was lab work from the text in the article here - I only assessed the sources' types and didn't delve into their content. If evidence is weak that should be stated, and there may be a case for omitting it. Another consideration is that Pharmazie is rather a low impact[2] journal. Bon courage (talk) 09:52, 30 December 2023 (UTC)

Thank you! What is your conclusion then? Should we mention that berberine inhibits the activity of CYP3A4? If yes, how should we mention it, addressing the issues you've raised? Maxim Masiutin (talk) 10:09, 30 December 2023 (UTC)

I think either (a) mention this material with appropriate caveats, or (b) omit it. I have no preference. Bon courage (talk) 11:49, 30 December 2023 (UTC)

OK, let us omit it until we collect better evidence in the future (to reach the consensus with Zefr).

As about my complaint about the edit warring, the administrators concluded that there was No violation – there must be four or more reverts within a 24 hour period for the 3-Revert Rule to apply; the links you have provided do not meet these criteria. Which does not absolve Zefr of their responsibility to take it up on talk.

I will watch future publications and will add information if it will be solid. Maxim Masiutin (talk) 13:54, 30 December 2023 (UTC)

@Zefr: I am happy that we reached consensus on the talk page. You were right on substance. Sorry that I was wrong. The only think that I didn't like about our consensus-building is edit warring. It would have been productive to explain on the talk page after the first revert or even before reverting, as I did in Talk:Hydroxyzine#Remove_information_baked_by_primary_sources_only. I first raised the issue, inserted inline templates, and then, after 12 days passed, deleted the improper claims. Maxim Masiutin (talk) 14:54, 30 December 2023 (UTC)

Not all edits or reverts require a talk page discussion. Clear edit summaries, WP:ES, should be sufficient unless a topic has genuine controversy. In my edit summaries on the berberine article, I used descriptions of the sources like "weak", "conjecture", "primary", non-MEDRS, etc., which are usually sufficient to show the content and sources are disputable and too vague for the encyclopedia. "The burden to demonstrate verifiability lies with the editor who adds or restores material - burden was not met for your sources.

You provided a correct revert and edit summary today on the hydroxyzine article. Well done. Zefr (talk) 15:31, 30 December 2023 (UTC)

Thank you very much for the appraisal for hydroxyzine. If I see vandalism or addition of unsourced information about a living person or when an edit is the only addition of square bracket around a word to a make disambiguation page link, I revert immediately. I am also a pending changes reviewer, but I try to be a cooperative collegue editor, not a policeman who follows the rules strictly.

But if I notice inappropriate health claim which stayed for months, I prefer to discuss on a talk page. It would not harm to keep questionable statements for yet few days if it already stayed a few months, and people are less enraged if you talk first, compared to when you revert first. When I write on a talk page, people can think a few days, calm down or find arguments or find better sources. So I try to behave friendly and not in a hurry. Maxim Masiutin (talk) 19:15, 30 December 2023 (UTC)