Finding some negatives on Berberine (I wi... - Cure Parkinson's

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Finding some negatives on Berberine (I will keep digging)

Bolt_Upright profile image

I was digging in a very positive Berberine article: Berberine: A Promising Treatment for Neurodegenerative Diseases 2022

When I came across this: "Meanwhile, there are several studies offer some important insights into the neurotoxic effects of berberine. It is reported that in the Parkinson’s disease model rats induced by 6-OHDA, berberine aggravate the degeneration of dopaminergic neuron in the substantia nigra of rats (Shin et al., 2013). In addition, berberine can aggravate the cytotoxicity induced by 6-OHDA in PC12 cells and aggravate of dopaminergic neuron death (Kwon et al., 2010)."

So... these are the referenced articles:

Neurotoxic effects of berberine on long-term L-DOPA administration in 6-hydroxydopamine-lesioned rat model of Parkinson's disease 2013 pubmed.ncbi.nlm.nih.gov/235... "However, both concentrations of berberine in 6-OHDA-lesioned groups treated with L-DOPA aggravated the numbers of TH-immunopositive neurons in the substantia nigra and the levels of dopamine, norepinephrine, DOPAC and HVA in the striatum as compared to rats not treated with berberine. These results suggest that berberine leads to the degeneration of dopaminergic neuronal cells in the substantia nigra in the rat model of PD with chronic L-DOPA administration. Long-term L-DOPA therapy that may involve possibly neurotoxic isoquinoline agents including berberine should involve monitoring for adverse symptoms."

Effects of berberine on 6-hydroxydopamine-induced neurotoxicity in PC12 cells and a rat model of Parkinson's disease 2010 pubmed.ncbi.nlm.nih.gov/208... "In addition, treatment with berberine (5 and 30mg/kg, i.p.) for 21 days in 6-OHDA-lesioned rats markedly depleted tyrosine hydroxylase-immunopositive cells in the substantia nigra as compared to berberine-untreated rats. Further, the levels of dopamine and norepinephrine were also significantly decreased by berberine administration (5 and 30mg/kg) in the striatal regions of 6-OHDA-lesioned rats. These results suggested that berberine aggravated 6-OHDA-induced cytotoxicity in PC12 cells, and led to the degeneration of dopaminergic neuronal cells in the substantia nigra of 6-OHDA-lesioned rats. It is, therefore, suggested that the use of long-term l-DOPA therapy with isoquinoline derivatives including berberine may need to be examined for the presence of adverse symptoms."

I will keep digging.

47 Replies

Mitochondria and NMDA Receptor-Dependent Toxicity of Berberine Sensitizes Neurons to Glutamate and Rotenone Injury 2014 journals.plos.org/plosone/a...

"Our study confirms previous reports on the neurotoxicity of BBR [19], [57] and suggests a mechanistic basis to understand how BBR could enhance neurodegenerative processes. These findings raise concerns over the CNS safety profile of BBR, particularly when used in the long-term in the aging population, in patients at risk of silent strokes or ischemic episodes [71], or in people at risk of chronic systemic pesticide exposure [50], [72]. Importantly, our results also suggest that memantine, a clinically available NMDA receptor antagonist, may be used to protect neurons against BBR toxicity. Widely available nutraceuticals and dietary supplements have gained considerable interest due to their potential health effects and presumed safety. However, more attention should be paid to both regulatory and research needs in this field."

"Mitochondria and NMDA Receptor-Dependent Toxicity of Berberine Sensitizes Neurons to Glutamate and Rotenone Injury [particularly in people at risk of chronic systemic pesticide exposure]." This is not good.

They just acknowledged the method of toxicity in organophosphate pesticides. This is why NMDAR antagonists like Memantine are therapeutic across the spectrum of NDDs and neuropsychiatric disorders like autism, ADD/ADHD/OCD, depression, anxiety...

Could you please explain this to me like the idiot I am? :)

You're not an idiot! I appreciate your self depreciation [I only have a high school education] but don't sell yourself short. You can't earn a degree for common sense.

I had a different experience than most people on this forum and therefore a reason to look for causation (I'm the Canary in the coal mine). Having this background has given me insight into pathogenesis of some chemicals. Those with advanced degrees lack real world experience. It's theoretical science for them - I am living proof and no one can trump this, they've tried.

So... "They just acknowledged the method of toxicity in organophosphate pesticides." means Berberine is toxic?

But "This is why NMDAR antagonists like Memantine are therapeutic across the spectrum of NDDs and neuropsychiatric disorders like autism, ADD/ADHD/OCD, depression, anxiety..." is saying Berberine is still good for you?

"They just acknowledged the method of toxicity in organophosphate pesticides." means Berberine is toxic?" YES, via this biological process: Mitochondria and NMDA Receptor-Dependent Toxicity of Berberine Sensitizes Neurons to Glutamate and Rotenone Injury [particularly in people at risk of chronic systemic pesticide exposure]."

"This is why NMDAR antagonists like Memantine are therapeutic across the spectrum of NDDs and neuropsychiatric disorders like autism, ADD/ADHD/OCD, depression, anxiety..." is saying Berberine is still good for you? NO. I wouldn't take it given my history of pesticide poisoning. Memantine is being under utilized and has a wide range of uses beyond Alzheimer's dementia.

I'm taking memantine along with rytary and metoprolol.

Thanks for the explanation. Berberine is still off my list.

good find

Thanks for reporting this. That certainly takes it off my menu of options.

MBAnderson profile image
MBAnderson in reply to park_bear

So, if we are dismissive of mice studies when they report a "break thru" why change our menu based on this mouse study?

park_bear profile image
park_bear in reply to MBAnderson

I am dismissive of animal studies that involve pretreatment because they are not valid models of Parkinson's. I am not dismissive of animal studies that involve treatment after toxic insult and a Parkinson's -like condition has been established.

In the current case we have studies attributing adverse effects on Parkinson's to this treatment. There are plenty of candidate substances that do suffer from such effects.

MBAnderson profile image
MBAnderson in reply to park_bear

Thanks.

This 2014 study bothered me too. And the point of their paper seemed to be "Hey! Everybody's taking Berberine. Maybe be careful with that!": Mitochondria and NMDA Receptor-Dependent Toxicity of Berberine Sensitizes Neurons to Glutamate and Rotenone Injury journals.plos.org/plosone/a...

- We report that low micromolar berberine causes rapid mitochondria-dependent toxicity in primary neurons characterized by mitochondrial swelling, increased oxidative stress, decreased mitochondrial membrane potential and depletion of ATP content.

- Subtoxic nanomolar concentrations of berberine were sufficient to sensitize neurons to glutamate excitotoxicity and rotenone injury.

- Our study highlights the need for further safety assessment of berberine, especially due to its tendency to accumulate in the CNS and the risk of potential neurotoxicity as a consequence of increasing bioavailability of berberine.

- Pharmacological data suggest that berberine has poor bioavailability and that only nanomolar plasma concentrations are reached in both humans and animals [20]. According to several reports, however, BBR accumulates in organs such as lungs, liver and the brain, resulting in effective concentrations in the low micromolar range.

- Our study raises concerns of acute BBR neurotoxicity due to its prominent effects on mitochondria and NMDA receptors, especially when applied at micromolar concentrations close to the levels suggested to be attainable by oral dosing.

- Recently, Pereira et al. characterized the effects of BBR on melanoma cell mitochondria as well as isolated mitochondrial fractions [22], [35]. They demonstrated that BBR can accumulate in mitochondria causing mitochondrial depolarization and fragmentation, mitochondrial PTP induction, increased oxidative stress, decreased cellular ATP content, and cell cycle arrest [35]. Our results from primary neurons support these findings. While these effects may be desirable for antitumor agents, they may also cause toxicity in neurons, which are sensitive to metabolic disturbances and thus particularly sensitive to mitochondrial dysfunction [40], [41], [63], [66]. Our current results suggest that mitochondria are centrally involved in the toxic effects of BBR in neurons.

One key point seems to be that, while BBR is not very bio-available, over time it accumulates in the brain.

Right now determining whether it is good or bad seems like a coin flip. As PB mentioned, we have other options that don't have the bad side of the coin. I will keep digging. I would love it if BBR was the answer.

did big pharma fund this? I read that it doesnt mix with big pharma's chemical pills...the articles were long and confusing...I would trust a natural product over big pharmas concoctions...all of which have their own nasty side effects...and why all these studies on a pill that few even know about? wheres all the research studies on big pharma's pills? I smell a rat but thats just my opinion I could be wrong

Their paper says no conflicting interests. It was done by a university in Finland. Interestingly, I corresponded with one of the researchers and testing BBR for neurotoxicity was not the point of their experiment. It just presented itself. I don't know what the original point of the study was.

But it is always a good idea to question motives.

so who paid for it? and what was their purpose of the study...thanks appreciate your hard work

Sorry, I don't have that information.

Gigi216 profile image
Gigi216 in reply to Bolt_Upright

You won’t believe this but I just took a little berberine! Needless to say I’m nervous about that and will not be taking any more. I have covid AGAIN and was taking it for congestion. Thanks for finding this!

Bolt_Upright profile image
Bolt_Upright in reply to Gigi216

I would not worry about it. Berberine is not very bioavailable. I think it takes a while to build up to any meaningful level in the brain.

JCRO profile image
JCRO in reply to park_bear

Thank you for taking the time. Bolt too. J

Thank you so much Bolt. I have been taking it but will now stop thanks to your fantastic research. So grateful to you always

would you share the positive reports too?

Sure Marc. I was writing up the notes from last week's Berberine review. These note are not complete. I paused when I started finding stuff about Berberine being neurotoxic:

Berberine Update 2022-06-26

Berberine Precautions and Drug Interactions: rxlist.com/berberine/supple...

Precautions:

• Children: It's UNSAFE to give berberine to newborns. It can cause kernicterus, a rare type of brain damage that can occur in newborns who have severe jaundice. Jaundice is yellowing of the skin caused by too much bilirubin in the blood. Bilirubin is a chemical that is produced when the old red cells break down. It is normally removed by the liver. Berberine may keep the liver from removing bilirubin fast enough.

• Pregnancy and breast-feeding: It's UNSAFE to take berberine by mouth if you are pregnant. Researchers believe berberine can cross the placenta and might cause harm to the fetus. Kernicterus, a type of brain damage, has developed in newborn infants exposed to berberine.

It's also UNSAFE to take berberine if you are breast-feeding. Berberine can be transferred to the infant through breast milk, and it might cause harm.

• Diabetes: Berberine can lower blood sugar. Theoretically, berberine may cause blood sugar to become too low if taken by diabetics who are controlling their blood sugar with insulin or medications. Use with caution in people with diabetes.

• High bilirubin levels in the blood in infants: Bilirubin is a chemical that is produced when the old red blood cells break down. It is normally removed by the liver. Berberine may keep the liver from removing bilirubin fast enough. This can cause brain problems, especially in infants with high levels of bilirubin in the blood. Avoid using.

• Low blood pressure: Berberine might lower blood pressure. Use with caution in people with low blood pressure.

There are quite a few Berberine drug interactions (This list may not be complete):

• Cyclosporine (Neoral, Sandimmune) Interaction Rating: Major Do not take this combination.

The body breaks down cyclosporine (Neoral, Sandimmune) to get rid of it. Berberine might decrease how fast the body breaks down cyclosporine (Neoral, Sandimmune). Cyclosporine (Neoral, Sandimmune) might build up in the body and could possible cause side effects. Cyclosporine is used for people with organ transplants.

• Medications for diabetes (Antidiabetes drugs) Interaction Rating: Major Do not take this combination.

Berberine might lower blood sugar. Diabetes medications are also used to lower blood sugar. Taking berberine along with diabetes medications might cause your blood sugar to go too low. Monitor your blood sugar closely. The dose of your diabetes medication might need to be changed.

Some medications used for diabetes include glimepiride (Amaryl), glyburide (Diabeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), and others.

• Dextromethorphan (Robitussin DM, and others) Interaction Rating: Moderate Be cautious with this combination. Talk with your health provider.

The body breaks down dextromethorphan (Robitussin DM, others) to get rid of it. Berberine might decrease how quickly the body breaks down dextromethorphan (Robitussin DM, others). Taking berberine while taking dextromethorphan (Robitussin DM, others) might increase the effects and side effects of dextromethorphan (Robitussin DM, others).

• Losartan (Cozaar) Interaction Rating: Moderate Be cautious with this combination. Talk with your health provider.

The liver activates losartan (Cozaar) to make it work. Berberine might decrease how quickly the body breaks down losartan (Cozaar). Taking berberine while taking losartan (Cozaar) might decrease the effects of losartan.

• Medications changed by the liver (Cytochrome P450 2C9 [CYP2C9] substrates) Interaction Rating: Moderate Be cautious with this combination. Talk with your health provider.

Some medications are changed and broken down by the liver. Berberine might decrease how quickly the liver breaks down some medications. Taking berberine along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking berberine, talk to your healthcare provider if you are taking any medications that are changed by the liver.

Some medications changed by the liver include celecoxib (Celebrex), diclofenac (Voltaren), fluvastatin (Lescol), glipizide (Glucotrol), ibuprofen (Advil, Motrin), irbesartan (Avapro), losartan (Cozaar), phenytoin (Dilantin), piroxicam (Feldene), tamoxifen (Nolvadex), tolbutamide (Tolinase), torsemide (Demadex), and S-warfarin (Coumadin).

• Medications changed by the liver (Cytochrome P450 2D6 [CYP2D6] substrates) Interaction Rating: Moderate Be cautious with this combination. Talk with your health provider.

Some medications are changed and broken down by the liver. Berberine might decrease how quickly the liver breaks down some medications. Taking berberine along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking berberine, talk to your healthcare provider if you are taking any medications that are changed by the liver.

Some medications changed by the liver include amitriptyline (Elavil), codeine, desipramine (Norpramin), flecainide (Tambocor), haloperidol (Haldol), imipramine (Tofranil), metoprolol (Lopressor, Toprol XL), ondansetron (Zofran), paroxetine (Paxil), risperidone (Risperdal), tramadol (Ultram), venlafaxine (Effexor), and others.

• Medications changed by the liver (Cytochrome P450 3A4 [CYP3A4] substrates) Interaction Rating: Moderate Be cautious with this combination. Talk with your health provider.

Some medications are changed and broken down by the liver. Berberine might decrease how quickly the liver breaks down some medications. Taking berberine along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking berberine, talk to your healthcare provider if you are taking any medications that are changed by the liver.

Some medications changed by the liver include cyclosporin (Neoral, Sandimmune), lovastatin (Mevacor), clarithromycin (Biaxin), indinavir (Crixivan), sildenafil (Viagra), triazolam (Halcion), and many others.

• Medications for high blood pressure (Antihypertensive drugs) Interaction Rating: Moderate Be cautious with this combination. Talk with your health provider.

Berberine might decrease blood pressure in some people. Taking berberine along with medications used for lowering high blood pressure might cause your blood pressure to go too low. However, it's not known if this is a big concern. Do not take too much berberine if you are taking medications for high blood pressure.

Some medications for high blood pressure include include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), amlodipine (Norvasc), hydrochlorothiazide (HydroDIURIL), furosemide (Lasix), and many others.

• Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs) Interaction Rating: Moderate Be cautious with this combination. Talk with your health provider.

Berberine might slow blood clotting. Taking berberine along with medications that also slow clotting might increase the chances of bruising and bleeding.

Some medications that slow blood clotting include aspirin, cilostazol (Pletal), clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), and others.

• Midazolam (Versed) Interaction Rating: Moderate Be cautious with this combination. Talk with your health provider.

The body breaks down midazolam (Versed) to get rid of it. Berberine can decrease how quickly the body breaks down midazolam (Versed). Taking berberine along with midazolam (Versed) might increase the effects and side effects of midazolam (Versed).

• Sedative medications (CNS depressants) Interaction Rating: Moderate Be cautious with this combination. Talk with your health provider.

Berberine might cause sleepiness and drowsiness. Medications that cause sleepiness are called sedatives. Taking berberine along with sedative medications might cause too much sleepiness.

Some sedative medications include benzodiazepines, pentobarbital (Nembutal), phenobarbital (Luminal), secobarbital (Seconal), thiopental (Pentothal), fentanyl (Duragesic, Sublimaze), morphine, propofol (Diprivan), and others.

Benefits of Berberine:

1. Lowers blood glucose levels (1).

2. Reduces insulin resistance (2).

3. Regulate blood glucose and blood lipid (2).

4. Reduce the level of inflammatory response in the body (2).

5. Berberine is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism (3).

6. Boosts brain function (4).

7. Can suppress the expression of inflammatory factors in PD patients and improve the disorder of intestinal flora (5).

8. Oral administration of berberine hydrochloride can trigger the biosynthesis of BH4 in the intestinal flora, increase the blood and brain dopa/dopamine concentration to enhance TH activity to produce L-dopa (5).

9. After treatment, the levels of IL-8, IL-6, and TNF-α were lower in the observation group than those in the control group (5).

10. Recent evidence suggests that berberine inhibits the production of neuroinflammation, oxidative, and endoplasmic reticulum stress (6).

11. Berberine normalizes the production of inflammatory factors, such as tumor necrosis factor-alpha (TNF-α), IL-6, IL-1β (6).

12. Berberine inhibits cell death induced by 6-OHDA, and increases the expression of HO-1, ultimately protecting dopaminergic neurons (6).

13.

Refferences

1. Berberine Drug Interactions: rxlist.com/berberine/supple...

2. Effects of berberine on glucose-lipid metabolism, inflammatory factors and insulin resistance in patients with metabolic syndrome ncbi.nlm.nih.gov/pmc/articl...

3. Efficacy of Berberine in Patients with Type 2 Diabetes ncbi.nlm.nih.gov/pmc/articl...

4. Plant Compound Berberine May Boost Brain Function parkinsonsnewstoday.com/new...

5. Effect of Berberine Hydrochloride on the Diversity of Intestinal Flora in Parkinson’s Disease Patients hindawi.com/journals/cmmi/2...

6. Berberine: A Promising Treatment for Neurodegenerative Diseases 2022 frontiersin.org/articles/10...

7. Therapeutic Efficacies of Berberine against Neurological Disorders: An Update of Pharmacological Effects and Mechanisms mdpi-res.com/d_attachment/c...

8. Berberine Is a Promising Alkaloid to Attenuate Iron Toxicity Efficiently in Iron-Overloaded Mice journals.sagepub.com/doi/fu...

9. Protective effects of berberine against MPTP-induced dopaminergic neuron injury through promoting autophagy in mice pubs.rsc.org/en/content/art...

10. Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota nature.com/articles/s41392-...

11. Interactions between gut microbiota and berberine, a necessary procedure to understand the mechanisms of berberine sciencedirect.com/science/a...

tanks

ships

For me the positives still out weigh the negative.

My spouse is on 250mg twice a day, three weeks now and I am going to ‘keep on keeping on’.

Going to occasionally switch out like I do on all of my supplements.

Learnt a long time ago, ‘there is no free lunch’

Thanks for the heads up 🌺

As with almost every study re PD, there are conflicting studies about berberine. I am not quite ready to quit it. (While this is an article and not a study, it cites studies.)

healthline.com/nutrition/be...

Thanks Marc, that is an interesting read.

I sent your stuff to Healthline. We'll see if & how they respond.

Awesome! That is great! I have to say that I think and thought, and it is all subjective, but I thought I felt a difference for the better when I started Berberine.

Maybe Berberine is not a risk. Or maybe I need to just take it once or twice a week? Maybe weekends? Maybe one weekend a month? Maybe this is why people say to take breaks?

I feel it maybe of benefit and am going to stick with it while doing more research.

(I added it about a month ago and had my annual physical at he VA yesterday and my blood pressure was 100 over 61.)

Bolt,

I am not sure why you are going back and looking at older animal studies when newer human studies do not confirm the animal studies regarding berberine. In this recent human study, they used a dose that would be a human equivalent dose to the doses used in the animal PD model for 3 months and, btw, this is a low dose compared to the dosing used in other berberine studies. What it showed is that it corrected some gut biome irregularities and it significantly reduced the inflammatory mediators IL-6, IL-8 and TNF-alpha. It is already established that all three of these inflammatory mediators and gut dysbiosis have a negative impact on PD patients including neuronal damage.

After 3 months of 3 times per day application of berberine to these patients, I think if increased neuron damage was occurring there would have been an overall negative impact in these patients in terms of day to day activities and function, but such was not reported in the study.

pubmed.ncbi.nlm.nih.gov/356...

Look at the graph in the study showing the inflammatory marker levels. These are substantial reductions that would be good for any person with a disease that has elevated inflammatory levels and in the case of PD, would likely slow the disease process. Based on other non PD/ berberine studies, they got these results with a relatively low dose of berberine in the PD patients. One can only wonder what those inflammatory marker levels would have been had they used a dose similar to what is used in human diabetes/berberine and other studies.

One reason why I feel that the animal PD model study does not apply to humans is because it is already established that berberine in humans has very poor bioavailability and as such the majority of its beneficial effects are thought to be provided through gut biome manipulation while very little of the berberine goes into circulation. Berberine in humans has less than 1% bioavailability.

Art

Thanks Art. The reason I glomed onto this is because the paper I was reading was from May 2022 and positive, and with all of the positive information these doctors felt the need to include the information on neurotoxicity: Berberine: A Promising Treatment for Neurodegenerative Diseases frontiersin.org/articles/10...

"3.2 Parkinson’s Disease

Parkinson’s disease, a neurodegenerative disease characterized by muscle stiffness, tremor, speech and gait changes, and its risk factors include environmental factors, genetic factors, gender factors, age, etc. (Kalia and Lang, 2015; Hou et al., 2019). At present, the therapy of Parkinson’s disease mainly uses dopamine agonists and MAO-B inhibitors to suppress the decomposition of dopamine, but they only target symptoms and have serious side effects (Jiang et al., 2015a). In the transcriptomics of Microsporum canis, there are 6 signaling pathways that have significant changes in Gene Ontology functional enrichment analysis after berberine treatment, including steroid biosynthesis, steroid hormone biosynthesis, Parkinson’s disease, 2,4-Dichlorobenzoic acid (2,4-DCBA) degradation and biosynthesis of tropane, piperidine and isoquinoline alkaloids (Xiao et al., 2015).

Previous studies have found that berberine inhibits cell death induced by 6-OHDA, and increases the expression of HO-1, ultimately protecting dopaminergic neurons (Bae et al., 2013). In SH-SY5Y cells, berberine suppressed 6-OHDA-induced ROS production, caspase-3 activation, and cell death (Bae et al., 2013). These indicate that berberine can be used as an effective therapeutic agent for dopaminergic neuron degeneration. In MPTP/P-induced mouse model of Parkinson’s disease, berberine reduced neuron loss in the substantia nigra pars compacta, dopaminergic fiber loss in the striatum, and apoptosis in the hippocampus. Animal behavior experiments have shown that the disorder of movement balance and coordination has been improved (Kim et al., 2014). However, when berberine is long-term administered to 6-OHDA-induced rat model of Parkinson’s disease, monitoring for adverse symptoms is required. Preclinical studies have found that berberine increases the number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra, at the same time, berberine also increases striatum dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid levels (Shin et al., 2013). Berberine is a potential therapeutic drug for alleviating motor dysfunction and memory impairment in patients with Parkinson’s disease (Kim et al., 2014). Meanwhile, there are several studies offer some important insights into the neurotoxic effects of berberine. It is reported that in the Parkinson’s disease model rats induced by 6-OHDA, berberine aggravate the degeneration of dopaminergic neuron in the substantia nigra of rats (Shin et al., 2013). In addition, berberine can aggravate the cytotoxicity induced by 6-OHDA in PC12 cells and aggravate of dopaminergic neuron death (Kwon et al., 2010).

Interestingly, Wang et al. pointed out that the application of berberine in Parkinson’s disease may up-regulate the synthesis of L-dopa in the intestinal microbiota through vitamin-like effects, thereby exerting a therapeutic effect (Wang Y. et al., 2021a). Besides, berberine can prevent NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome from being activated during the inflammation process of Parkinson’s disease and restore autophagy activity to protect dopamine neurons (Huang et al., 2020).

In addition to the above studies, in the zebrafish Parkinson’s disease model, berberine derivatives can be used to treat Parkinson’s disease. This is because berberine derivatives can cross the blood-brain barrier and target mitochondria in the meantime (Wang L. et al., 2021b)."

That bolded (bolded by me) section gave me pause.

Bolt,

I think the inflammatory mediators are doing as much or more damage in the brain and body than the PD animal models showed from berberine.

If the animal model applied to humans in this case, then I think that the people with diabetes who have been taking berberine at high dose for years as part of their treatment would already being showing signs of PD as people with diabetes are at 31% greater risk for PD. Diabetics using berberine are using a very significantly higher dose of berberine than the human converted dose from the animal PD model studies. We are not seeing studies or reports confirming that diabetics using high dose berberine are increasing the rate of PD conversions.

I think it would be a bad idea to assume that rats and humans have the same gut microbiome, they don't.

Art

Thank you very much Bolt. I have been taking Berberine for a little while. I never was 200% sure it really helped and have now taken it off my list (I am probably taking too many things anyway!),

Please do.

Hi, I’m 50 diagnosed with PD two years ago taking many supplements. Amongst others Metmorphine, which is supposedly the chemical equivalent of Berberine if I’m not mistaken. Do you have any reports on the effects of Metmorphine on PWP?

Bolt_Upright profile image
Bolt_Upright in reply to MAJ88

I did a quick Google of neurotoxicity metformin and only found good news, but would really need to dig into it. While Berberine and Metformin have similar effects on glucose, I don't think they are similar. I would defer to your health professionals.

MAJ88 profile image
MAJ88 in reply to Bolt_Upright

Thank you very much! Further feedback very appreciated. I’ll stick to it, therefore, in the message.

I am flip flopping like others... On Berberine... and now after reading... OFF! Thanks Bolt

THANKS SOOOOOO MUCH Bolt! I just started taking Berberine LAST MONTH because of the good reports i read on this site... NOW... I just got a REFUND from Amazon on my purchase! ... ---------------

KEEP UP THE GREAT POSTING, BOLT!

I reached out to somebody involved in this 2014 study: Mitochondria and NMDA Receptor-Dependent Toxicity of Berberine Sensitizes Neurons to Glutamate and Rotenone Injury journals.plos.org/plosone/a...

I don't share personal correspondence, but I can paraphrase:

1- The purpose of the study was not to look for Berberine neurotoxicity. They were surprised to find it.

2 - They were confident of their results.

3 - There is an open question of whether BBR can build up to the micromolar level in the brain needed to cause toxicity, but this happening would not be surprising, especially in older people with slower metabolisms and leaky blood brain barriers.

4 - They would not recommend Berberine to their family members.

They said something else interesting to my question of their belief on Berberine neurotoxicity: They said that data is the key to understanding. Belief can be harmful to the scientific process.

Berberine is off of my stack.

Blow what to do ? Been taking Berberine for both diabetes and PD ....?

Keep in mind that I have a high school degree. Trust yourself and your health professionals.

I 'minored' in biochem but this was nearly 40 years ago. Wiki says, "Berberine is an alkaloid derived from tyrosine. L-DOPA and 4-hydroxypyruvic acid both come from L-tyrosine...' So Berberine makes dopamine? What little I know about medicines is that dosage is critical; Too much or too little have the same effect. Meaning no effect. The article talks about nano-levels of medication. What's smaller than nano? What's larger?

Interesting that these studies examine long term Levodopa together with berberine treatment. What about NO Levodopa, then what?

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