Metformin rescues Parkinson's disease phenotypes caused by hyperactive mitochondria pubmed.ncbi.nlm.nih.gov/330...
Metformin Use Linked to Increased Dementia, Parkinson's Risk in Patients With Diabetes medscape.com/viewarticle/87...
If Metformin can reverse aging it makes s... - Cure Parkinson's
If Metformin can reverse aging it makes sense that it could reverse PD, but studies have shown increased risk. Puzzled
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Gcf51
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Ask yourself why they were taking metformin. It was for insulin resistance , diabetes. The insulin resistance increases the risk of neurodegeneration. A study of metformin used in pd in the absence of insulin resistance has not been done to my knowledge
park_bear• in reply to
Not so simple:
"After adjustment for factors such as age, sex, and diabetes severity, "the cumulative incidences of Parkinson's and dementia were significantly higher for our metformin cohort" at 12 years (P < .001), reported Dr Kuan.
Table 1. Outcomes in Metformin Users vs Nonusers
Outcome Event Rate (%) Adjusted Hazard Ratio (95% Confidence Interval)
PD ............... 6.85 vs 2.78 ............................... 2.27 (1.66 - 3.07)"
• in reply topark_bear
Are you familiar with the TAME trial?
science.org/content/article...
“Not so simple” you said
Never did a say or imply I was expressing the full picture on this but what I did state is factual.
That said, I’m more interested in Rapamycin
park_bear• in reply to
Users of metaformin and non users both had diabetes: "After adjustment for factors such as age, sex, and diabetes severity". The studies you cited do not contradict this finding.
• in reply topark_bear
To be clear, do not contradict what finding? That metformin causes dementia?
park_bear• in reply to
The point of the cited study is Metformin is adverse for Parkinson's.
• in reply topark_bear
According to the TAME trial? I had remembered it incorrectly than.
park_bear• in reply to
no, this:
medscape.com/viewarticle/87...
• in reply topark_bear
The same one as referenced before from 2017. I was introducing another massive study that is ongoing. One of the intentions of which is to see if metformin is brain protective which is why I’m sharing it.
I did the unthinkable. I found online a site which has doctors that issue prescriptions after a online questionnaire. I have been taking metformin for a week. I feel very positive that it is helping.
Good for you taking control of your treatment. Glad to hear your positive experience.
I was just prescribed metformin. Central diabetes with high serum insulin (due to toxic hypothalamic injury - my opinion).
Thinking about shooting some insulin up my nose and into my brain too. Maybe we need to form a subgroup - self hackers anonymous, lol.
SE
• in reply toGcf51
That’s great!!
The potential role of metformin in the treatment of Parkinson's disease 2020 journals.lww.com/jbioxresea...
"An epidemiological investigation into insulin resistance revealed a significant increase in body weight in PD patients after diagnosis.[50] In PD patients with dementia, 30% had impaired glucose tolerance, 5.6% were diagnosed with diabetes, and 26% had insulin resistance only.[51] In addition, a phenomenon similar to the process of peripheral insulin resistance occurs in the brain of PD patients, suggesting that the insulin resistance may be an important factor in PD pathogenesis.[52] It has been shown that increased ferritin and impaired glucose homeostasis might increase the risk of diabetes,[53] and these ions are known to generate large amounts of free radicals via the Fenton reaction, thus causing the degeneration of dopaminergic neurons. "
"Studies have shown that anti-diabetic drugs promote neuronal survival, affect brain metabolism and nerve inflammation and regeneration, and lead to improved memory and cognition.[94] Therefore, antidiabetic drugs are potential therapeutic agents for the treatment of neurological diseases.[114] Metformin is a first-line hypoglycemic agent for the treatment of insulin-resistant (type 2) diabetes mellitus.[115] The role of metformin in cell metabolism, neuronal protection, and improvement of cognitive impairment suggests that metformin may alleviate, or even cure, PD-related symptoms (Fig. 3)."
I found the scary part:
"However, the long-term use of metformin slightly increases the risk of Alzheimer's disease and vascular dementia.[121,122] The decrease in BDNF suggests a potential state of vulnerability for the brain, as well as a decrease in neuroplasticity, which is necessary for enhanced cognitive effects. Long-term use of metformin reduces BDNF transcription and inhibits nuclear factor E2-related factor 2 (Nrf2), which may increase the vulnerability of the central nervous system.[123] Some studies have also suggested that metformin increases the risk of PD or even aggravates neuronal damage.[123] For example, metformin inhibited the MPTP-induced brain inflammatory response through iNOS, IL-1β, and TNF-α, affecting the microglia polarization state under conditions of neurodegeneration. However, MPTP and metformin may act in an additive manner to inhibit complex I of the electron transport chain in Parkinsonian patients, thus reducing ATP levels. Despite inflammatory parameters being decreased, a dose of MPTP lower than that of metformin may increase neuronal damage and exacerbate the vulnerability of neurons, which are particularly sensitive to the inhibition of complex I in the electron transport chain.[124]
Therefore, the indications for the safe use of this drug therapy should be carefully controlled for patients requiring long-term and high-dose treatment with metformin."
On the other hand, Berberine boosts BDNF: Pharmacological effects of berberine on mood disorders 2019 ncbi.nlm.nih.gov/pmc/articl...
". . .or even cure, PD-related symptoms (Fig. 3)."
Very bold statement, Bolt. I love it as this kind of statements are nonexistent.
Look into naringenin.
• in reply toHouse2
Neuroprotective effects if Apigenin and luteolin
Apigenin is another good one Found in diet. Best source is dried parsley. Can buy as supplements.
pubmed.ncbi.nlm.nih.gov/250...
Please share thoughts on Apigenin and Narigenin?
Narigenin:
NGN significantly downregulated SYN and upregulated dopamine transporter (DAT) and tyrosine hydroxylase (TH) protein expressions. It also downregulated tumor necrosis factor-α (TNFα) and interleukin 1β (IL1β) mRNA expressions and improved superoxide dismutase levels. It also reduced glutathione levels when compared to vehicle-treated PD animals. The upregulation of TH corroborates to an increase in dopamine, DOPAC, and homovanillic acid turnover and motor functions with NGN treatment. To summarize, NGN, a dietary flavone, has the potential to counteract MPTP-induced dopaminergic degeneration by regulating SYN pathology, neuroinflammation, and oxidative stress
Reduced glutathione, that’s not good
Note the mice received the NGN before the “Parkinson’s”
Any in human data?
I think metformin depletes vitamin B-12
Periodic screening for serum vitamin B12 levels should be done to identify metformin-induced B12 deficiency in T2DM, especially those with PN.
Kamrul-Hasan AB, Alam MS, Chanda PK, Selim S. Serum Vitamin B12 Levels in Patients with Type 2 Diabetes Mellitus on Metformin Compared to those Never on Metformin: A Cross-sectional Study from Bangladesh. Mymensingh Med J. 2021 Oct;30(4):913-920. PMID: 34605456.
Naringenin a flavonoid found in high concentrations as its glycone naringin in citrus fruits, has been reported to have antioxidant, antiatherogenic, anti- dyslipidemic and anti-diabetic effects. It has been shown that naringenin exerts its anti-diabetic effects by inhibition of gluconeogenesis through upregulations of AMPK hence metformin-like effects.
Nyane NA, Tlaila TB, Malefane TG, Ndwandwe DE, Owira PMO. Metformin-like antidiabetic, cardio-protective and non-glycemic effects of naringenin: Molecular and pharmacological insights. Eur J Pharmacol. 2017 May 15;803:103-111
I can only speak from the experience of use of Metformin by my mother. She was diagnosed with type 2 diabetes in her late 60 s. She was given Metformin which seemed to help her with the diabetes. My father being a mechanical engineer monitored her sugar levels with absolute precision! Fast forward to mid 70 s and my mum was diagnosed with PD. It seemed to progress relatively slowly at first and then she suffered a stroke and mild dementia. She died at age 84.
My husband has PD obviously no genetic connection to my mum.
Repeating a link and adding some questions. Metformin Use Linked to Increased Dementia, Parkinson's Risk in Patients With Diabetes medscape.com/viewarticle/87...
As I understand the study followed diabetics who took metformin and didn’t. Leaving the question, how about non-diabetics? Does insulin resistance increase the risk of neurodegeneration? Has a study of metformin use in Parkinson’s in the absence of insulin resistance has been done? On other the hand, why would insulin resistance flip the risk or make the risk nonexistent.
Hidden Bolt_Upright
• in reply toGcf51
I have the same questions and no answer. But, I linked a massive ongoing study bc the metformin story is ongoing and we really don’t know at this point. Rapamycin looks good so far and Urolthin A, and AKG
Apologies. We have reached the limit of my abilities on this topic.
You are right, Bolt. I second your motion. I am unable to follow all these "trials" with no tangible results. I used to be more aggressive in my searching, but no more. All I do is adding what the trials use, meds or supplements, to my hubby's stack, but no disease modifying results! Improvements? Yes.
You are a great person Despe. How is your husband doing?
Thanks, Bolt! 😗He is out right now shopping.
His posture is more scooped and he is still depressed and apathetic.
These are all the things I take to help with depression (I am still severely depressed but had some good hours yesterday):
Prozac (hope to get off that someday)
L-Methylfolate
Lithium Orotate
Saffron
Berberine
Nigella Sativa
Magnolia Bark Extract
All but the Prozac might help stave off PD also.
Good luck and may God bless you both.
You, too! We are trying to avoid anticholinergics. . . He is on most of the supplements you listed.
KSM-66 (Ashwagadha) helped tremendously with my depression and is suppose to be good for Parkinson's too. I do not have the same benefit from regular Ashwagadha Extract. I do take an antidepressant (mirtazapine 15mg) which my motion specialist said would help me sleep.
Thanks for the tip on Ashwaghanda. I have the extract, so good to know that did not help your depression. I am trying the lithium orotate and l-methylfolate right now.
Lithium orotate 5mg did improve my mood. I was taking every day with food. I started having loose stools and cut back to 3 a week. Mood is still good at 3 a week.
I haven't had brain fog since I started taking KSM-66 (Ashwagadha). Well... with Metformin I had Brain Fog. I will cut back and see if that helps, otherwise i will have to stop.
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