Natural alternative to Pioglitazon (Actos) which works on same pathways?

[linusbert]

originally i was prescribed Pioglitazon (also known as Actos) for my then arrising diabetes, but i learned soon that it actually improves my "cfs"-like disease a lot. despite also changing all blood markers to the better. i become much more exercise tolerant.

now after my diabetes is getting really good after changing my bread and vitamin D, i removed insulin completely and i am still in 5,6% a1c range. now i want to get rid of Pioglitazon because it has nasty effects and its not even long term studied. I suspect it to be responsible for my decline in GFR.

i changed from 30mg to 15mg and want to get down to at least 7,5 if i cannot get off completely (7,5 for diabetes is as effective as 30mg...), and while my sugar even did improve after that even more, my cfs-like symptoms are getting worse again. its only been approx 1,5 weeks since doing that, i still hope my body does adapt to new situation and it stabilizes.

pioglitazone works strongly on PPARy and is somewhat anabolic. but despite metformin which immediately makes me get into PEM and crash after just one day of low dose, this pio stuff turns some switches in my body for the better, or at least so it feels.
more on PPARy: https://en.wikipedia.org/wiki/PPAR_agonist

i wonder what natural things can have the same effect?

EDIT: thats what chatgpt ai has to say about it:

Spoiler

PPARγ (peroxisome proliferator-activated receptor gamma) is a nuclear receptor that plays a crucial role in the regulation of various metabolic processes, including adipogenesis (formation of fat cells) and insulin sensitivity. Natural PPARγ activators are compounds found in nature that can stimulate the activity of PPARγ. Some of these natural activators include:

1. Thiazolidinediones (TZDs): While not found directly in nature, certain pharmaceutical drugs like pioglitazone and rosiglitazone are synthetic PPARγ activators and are used in the treatment of type 2 diabetes.
2. Fatty acids and their derivatives: Certain fatty acids, particularly polyunsaturated fatty acids (PUFAs) such as linoleic acid and eicosapentaenoic acid (EPA), can activate PPARγ. Additionally, certain prostaglandins derived from arachidonic acid can also act as PPARγ activators.
3. Oleic acid: Found in olive oil, oleic acid is a monounsaturated fatty acid that has been reported to activate PPARγ.
4. Flavonoids: Some flavonoids, which are plant-derived polyphenolic compounds, have been shown to activate PPARγ. Examples include quercetin, kaempferol, and apigenin, which are found in fruits, vegetables, and beverages like tea.
5. Resveratrol: Found in red wine, grapes, and berries, resveratrol is a polyphenol that has been reported to have PPARγ-activating properties.
6. Curcumin: A compound found in turmeric, curcumin has anti-inflammatory and antioxidant properties and has been reported to activate PPARγ.
7. Lycopene: Found in tomatoes and other red fruits, lycopene is a carotenoid that may have PPARγ-activating properties.
8. Berberine: Derived from various plants, including berberis species, berberine has been studied for its potential to activate PPARγ and improve insulin sensitivity.

It's important to note that the effects of these natural compounds on PPARγ activation may vary, and the mechanisms by which they interact with PPARγ are complex. Additionally, while some studies suggest beneficial effects, more research is needed to fully understand the implications of PPARγ activation by these natural compounds and their potential therapeutic applications.

https://www.sciencedirect.com/science/article/pii/S0006295214004249

 

[lyran]

Have you tried Berberine?

 

[linusbert]

Have you tried Berberine?

yes, same as with metformin, zero tolerance.

 

[Judee]

This is what Perplexity.ai said when I asked it if Alpha Lipoic works on PPARy:

"Alpha-lipoic acid (ALA) has been found to enhance endogenous peroxisome-proliferator-activated receptor-gamma (PPAR-γ) to ameliorate conditions such as experimental autoimmune encephalomyelitis (EAE) in mice
1
. It has also been shown to up-regulate the expression of PPAR-γ in skeletal muscle
3
. Additionally, studies suggest that lipoic acid may reflect induction and activation of PPAR-γ coactivator-1alpha, indicating its impact on mitochondrial function in aging rats
5
. These findings indicate that alpha-lipoic acid works on PPAR-γ and may have potential therapeutic benefits for conditions associated with PPAR-γ dysfunction."

I have no clue what PPAR-y is. I just wondered because you brought it up and I see a lot of reviews online where people mention using ALA helping with their blood sugar levels. (It's also a chelator so care has to be taken by people with amalgams and heavy metals exposure. For that it has to be taken in a certain way and probably why a few people in the reviews said they reacted poorly to it. ??)

 

[shadowraith]

I do know that PPAR receptors affect muscle type switching. I was looking into modulators such as bocidelpar

 

[pattismith]

yes, same as with metformin, zero tolerance.

Hello,

did you find something to replace pioglitazone?

I wonder if Mirabegron could help you. I found many recent studies about it's ability to reduce insuline resistance

"In skeletal muscle, mirabegron reduced triglycerides, increased the expression of PPARγ coactivator 1 α (PGC1A) (P < 0.05), and increased type I fibers (P < 0.01). Conditioned media from adipocytes treated with mirabegron stimulated muscle fiber PGC1A expression in vitro (P < 0.001).CONCLUSIONMirabegron treatment substantially improved multiple measures of glucose homeostasis in obese, insulin-resistant humans. Since β cells and skeletal muscle do not express β3-ARs, these data suggest that the beiging of SC WAT by mirabegron reduces adipose tissue dysfunction, which enhances muscle oxidative capacity and improves β cell function."

Here I posted more about it and quoted some studies about it:

https://forums.phoenixrising.me/thr...e-cfs-aging-rapidly.62075/page-2#post-2461503

 

[linusbert]

did you find something to replace pioglitazone?

no

that reads interesting, but it has its own set of side effects. i would replace one medication with another. but i have it on my watch list.

thanks

 

[szrk]

Also not natural, unfortunately, but Lobeglitazone is a safer thiazolidinedione with far greater PPAR gamma agonism relative to other effects. Avoids the bladder cancer rate increase too seemingly. Only available in India and South Korea at the moment though. I'm trying some from a seller on Indiamart largely for non-CFS fat redistribution reasons. Neither it nor my brief trial of pioglitazone seem to be helping my CFS unfortunately. Still might be a decent option for someone else CFS wise.

 

[linusbert]

thanks will check out

 

[Judee]

@linusbert where you've said in other posts about carbs making you feel better, I wonder if you've looked into glycogen storage diseases. Some of the symptoms for at least one of them (iirc I think it is 5) seems very similar to ME/CFS.

???

 

[linusbert]

@linusbert where you've said in other posts about carbs making you feel better, I wonder if you've looked into glycogen storage diseases. Some of the symptoms for at least one of them (iirc I think it is 5) seems very similar to ME/CFS.

???

yes, metabolic myopathies and many myopathies are similiar to cfs.
but i do not have a confirmed diagnosis, they at one point made that differential diagnosis "metabolic" myopathy.