Update: Please see the replies below on the disastrous Deferiprone trial.
Berberine Is a Promising Alkaloid to Attenuate Iron Toxicity Efficiently in Iron-Overloaded Mice 2022 journals.sagepub.com/doi/fu...
"The results of this study show that the natural compound berberine demonstrates a superior ability to reduce excess iron and chelate it in tissues, including liver, kidney and lung. By reducing oxidative stress, it can also improve the activity of the antioxidant enzymes catalase and superoxide dismutase. This remarkable ability of berberine is comparable to and often superior to that of deferoxamine as a common chelator. Berberine was equally capable of reducing malondialdehyde and lipid peroxidation resulting from an iron overdose. Therefore, we recommend further in vivo studies on berberine as an iron chelator and an antioxidant compound in diseases associated with iron-overload."
"In recent clinical trials, iron chelation therapy has been shown to open the way to a treatment of Parkinson’s disease, PD, which potentially slows the disease progression. Many of these neurological disorders, including Alzheimer’s and Parkinson’s diseases, appear to be related to focal accumulation of iron in specific regions of the brain."
"Concluding Remarks: The underlying characteristics of Parkinson’s disease include neuroinflammation, the generation of ROS, and localised iron accumulation, particularly in the SN. The combined effects of inflammation on iron metabolism in glial cells and their toxic consequences on neurons suggest that therapeutic approaches that target the regulation of glial function may represent a promising approach to the treatment of iron-mediated neurodegenerative diseases, such as PD. Neuroinflammation would stimulate the classic iron-withholding response seen in the anaemia of chronic disease, which is reflected in the poor response to iron chelation therapy observed in our clinical trial [109] among PD patients with inflammation. This would also be in agreement with the observation that the long-term utilisation of non-steroid anti-inflammatory drugs protects from PD. Thus, a combined approach involving multi-target drugs, combining iron chelation, antioxidant, and anti-inflammatory properties may represent the way forward."
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This is great information. However, we need to look further upstream for what's causing the iron overload. The clue is in your article. Superoxide dismutase and Catalase deficiency. If you correct the deficiency you won't need to chelate iron. My 5¢
In the 2014 trial, Targeting Chelatable Iron as a Therapeutic Modality in Parkinson's Disease ncbi.nlm.nih.gov/pmc/articl... they show that improvements persisted for as long as they continued the chelation (18 months). Benefits waned after discontinuing treatment, indicating some iron accumulation parthenogenesis was still happening.
So... chelation might not address the cause, but might stop or slow progression for some amount of time. In the trial UPRDS got worse by 1 in the control and improved by 2 in the chelated group.
Of course this is all speculative. They did not use Berberine in the trial. I take Berberine anyway, so this is a bonus benefit.
You took berberine out of your stack last June. "The negatives came down to 2 rat studies and 1 in vitro study showing BBR is/could be neurotoxic at oral dosing levels [Personally, for me, the potential bad outweighs the potential good and I have removed Berberine from my stack (at least for now), "
Are you saying the potential benefit is outweighed by the potential harm?
Yes, I recently added Berberine back to my stack. I planned on writing about it soon.
Reminder to everybody: I have not been diagnosed with PD. I have RBD and a sore left shoulder and sore left leg. And sometimes face dandruff. I used to also have balance issues, get dizzy when I stood up, have occasional involuntary movements (now they are rare), and a stiff neck. Things may slowly be improving.
Back to Berberine: When I was on Berberine before it seemed to be helping. TMI but there was more mucus with my poop and I think that mucus is important. It was more than that, I just felt something.
Then I read some other good reports on Berberine:
Effects of Berberine on the Gastrointestinal Microbiota ncbi.nlm.nih.gov/labs/pmc/a... "Berberine can enrich the population of butyrate-producing bacteria in the GM"
Interactions between gut microbiota and berberine, a necessary procedure to understand the mechanisms of berberine sciencedirect.com/science/a...
Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota 2021 nature.com/articles/s41392-...
Therapeutic Efficacies of Berberine against Neurological Disorders: An Update of Pharmacological Effects and Mechanisms 2022 mdpi.com/2073-4409/11/5/796...
Effect of Berberine Hydrochloride on the Diversity of Intestinal Flora in Parkinson’s Disease Patients 2022 hindawi.com/journals/cmmi/2...
So yes, I do think there is a risk to Berberine. Also a risk if I do nothing. Most of my focus is on fixing the microbiome. BBR seems to be a good tool for accomplishing that.
Berberine Is a Promising Alkaloid to Attenuate Iron Toxicity Efficiently in Iron-Overloaded Mice
There currently are a number of chemical chelators in clinics to reduce iron concentration, for example,deferoxamine and deferiprone, but these produce diverse side effects. Hence, the need for a safe and effective iron chelator is demanded.
**Deferiprone has been in multiple trials for ND diseases.
Deferiprone reduces amyloid-β and tau phosphorylation levels but not reactive oxygen species generation in hippocampus of rabbits fed a cholesterol-enriched diet
Well done Little_apple ! From the article you linked to: Berberine Is a Promising Alkaloid to Attenuate Iron Toxicity Efficiently in Iron-Overloaded Mice
"Nowadays, synthetic iron chelators such as deferoxamine (DFO; Figure 1(A)) and deferiprone are used to chelate iron.11 These drugs exert many side effects, including patient irritation, and systemic allergic reactions, like rash, urticaria, anaphylactic response and angioedema.12,13 This highlights the need for research on new chelators. Therefore, today, researchers have focused their attention on organic compounds. Studies have shown that flavonoids, coumarins, chromones, anthocyanins and chalcones possess the chelating power of heavy metals.14,15 Thus, they can chelate intermediates such as iron in diseases like Parkinson’s, Huntington’s, Alzheimer’s and thalassemia. Berberine (Figure 1(B)) is an alkaloid found in the roots, stems and bark of plants such as Berberis (Berberis vulgaris). Therapeutically, berberine has long been used as an antibacterial compound in traditional medicine, especially in China to treat gastrointestinal infections and diarrhea.16,17 It is additionally utilized orally to decrease blood sugar and treat diabetes, lower blood fats and pressure. Berberine typically exerts no adverse side effects, but in some cases gastrointestinal upset has been observed with symptoms like diarrhea, bloating, constipation and stomach pain.18,19 In 2006, Shirwaikar et al. examined the antioxidant and chelating activity of berberine on lipids and antioxidant enzymes in vitro and showed that it possesses a superior ability to chelate iron, as well as reduce the effect of oxidants.20 In addition, in 2017, Polu and colleagues, by examining the antioxidant effects of Tinospora cordifolia, which contains an extensive amount of berberine, showed that this plant exerts good antioxidant effects and demonstrates an excellent ability to chelate iron in vitro.21 Zhao and colleagues also demonstrated that berberine, with its strong antioxidant power, possesses neuroprotective properties.22 Therefore, according to these studies, which represent the chelating and antioxidant activity of berberine, in this study, we investigated the iron chelating and antioxidant potency of berberine in the liver, lung and kidney tissues of iron-overloaded mice in vivo as a suitable alternative to chemical chelators."
That is a good point to raise. The Deferiprone trial went horribly.
Results: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants.
Conclusions: In participants with early Parkinson’s disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks.
"The team speculated that the iron-chelating effects of deferiprone may have reduced the activity of iron-dependent tyrosine hydroxylase, an enzyme critical for dopamine production.
As such, a deferiprone-induced drop in dopamine may have triggered symptoms instead of slowing disease progression. The higher prolactin levels detected in deferiprone-treated patients were consistent with this interpretation, they added."
“Despite evidence of target engagement of iron reduction in the substantia nigra of participants with Parkinson’s disease who had never received levodopa … deferiprone was not associated with benefit as compared with placebo in measures of the progression of Parkinson’s disease, and there was evidence of clinical worsening,” the researchers wrote.
“Whether participants receiving dopaminergic therapy would have a different outcome remains unclear, but in trials of deferiprone involving a total of approximately 240 participants who were receiving dopaminergic therapy, no worsening in scores of Parkinson’s disease activity was observed with this agent, and some participants even had improvement in such scores,” they added.
Among the multitude of pro health effects of melatonin for PD and many other health issues, iron chelation and protection from iron related oxidative stress is in its repertoire :
' Numerous studies have shown that melatonin has a high iron chelation ability and direct free radical scavenging activity, and can inhibit the lipid peroxidation process caused by iron overload. '
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Treg Cells Attenuate Neuroinflammation and Protect Neurons in a Mouse Model of Parkinson’s Disease. [This looks like an important article!]
BioVie announces treatment of 1st patient in Phase 2 clinical trial of NE3107,ERK inhibitor that selectively inhibits neuroinflammation
