Cyanidin-3-O-glucoside (C3G), the next polyphenolic StAR ?

[martybyrde]

Wondering if this thing is nuking my blood sugar. Lowered the dose today but so far still impressive improvements in many areas.

 

[Mauritio]

Update: loving this ***t. libido, energy/focus, mood, digestion, calming. Easily the best supplement I have used.

@Mauritio
5-6 tsp’s a day is where it’s at, although I seem to need more water than usual

Happy to hear that!

I think we have a similar response. I also notice that I need more water... not sure why. Maybe I evaporate more because of increased uncoupling. But with increased water intake and some more fiber my BMs are back to normal in terms of frequency, which are still green btw...but I have been having trouble with bile for like 3 months so hopefully it helps with that.

I notice that I have more energy and that I feel more androgenic and confident.
Yesterday I could not fall asleep and after some elderberry juice I was able to fall asleep easily. So this somehow is able to energize you but also calm you down.
My mood is definitely better as well, like I am more stress resistant and worry less.

The only downside is that my hair loss seems to increase a bit, but not strongly.

 

[Mauritio]

This study is fascinating.

So C3G increases bile excretion into feces (maybe thats why some people report black/green stool), but it also increases CYP7A1, which converts cholsterol into bile acid. Thyroid increases this enzyme as well.
Estrogen has the opposite effect on bile causing "stuck bile" a.k.a cholestasis. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606790/)

So you get less cholesterol, more bile, but also more bile excretion, which prevents old bile with toxic hydrophobic bile acids and estrogen metabolites to be reabsorbed too much. But that also makes it more important to make sure that you dont get constipated and I think that is the idea behind taking carrot salad or wheat bran, because it binds bile and helps speed up transit time.

"Results showed that cyanidin-3-O-β-glucoside consumption inhibited the formation of aortic sinus plaque and reduced hypercholesterolemia, along with promoted fecal bile acid excretion and upregulated hepatic cholesterol 7a-hydroxylase expression (CYP7A1). In mouse primary hepatocytes, cyanidin-3-O-β-glucoside treatment increased bile acid synthesis and CYP7A1 expression in a liver X receptor alpha (LXRα)-)-dependent manner. Scintillation proximity and time-resolved fluorescence resonance energy transfer assays revealed that cyanidin-3-O-β-glucoside functions as an agonist of LXRα."

- Cyanidin-3-O-β-glucoside upregulates hepatic cholesterol 7α-hydroxylase expression and reduces hypercholesterolemia in mice - PubMed


Increased bile acids will then have an anti-endotoxin effect.


"If the bile (bile acid) content of the intestinal canal decreases the endotoxin can translocate to the body and elicits toxic symptoms. So most important parts of defense against endotoxins in natural conditions are the CCK and bile acids. The consequence of damage of liver (place of bile acid synthesis) or small intestine (place of CCK synthesis) is the absorption of endotoxins."
- Role of endotoxins and bile acids in the pathogenesis of septic circulatory shock - PubMed

"The absorption of tritium-labeled Escherichia coli O89 Westphal-type endotoxin from the peritoneal cavity of rats was diminished by bile by 23% and by sodium deoxycholate by 47%, respectively."
- Effect of bile acids on the intestinal absorption of endotoxin in rats - PubMed

 

[Ben.]

Happy to hear that!

I think we have a similar response. I also notice that I need more water... not sure why. Maybe I evaporate more because of increased uncoupling. But with increased water intake and some more fiber my BMs are back to normal in terms of frequency, which are still green btw...but I have been having trouble with bile for like 3 months so hopefully it helps with that.

I notice that I have more energy and that I feel more androgenic and confident.
Yesterday I could not fall asleep and after some elderberry juice I was able to fall asleep easily. So this somehow is able to energize you but also calm you down.
My mood is definitely better as well, like I am more stress resistant and worry less.

The only downside is that my hair loss seems to increase a bit, but not strongly.

The bile/stool thing seems to be mentioned by others aswell on reddit.

In terms of hair i stumbled upon a theory about G3A ( cyanidin-3-o-arabinoside) which is apparantly found concentrated in chokeberries.

Looks like a real cure to the root of baldness (DHT-induced senescence) was proven earlier this year​

anthocyanines are interesting. Elderberry defeniately excerts a profound effect. Cant say i ever experienced that from blueberries.

 

[GTW]

Dried aronia/chokeberry readily available.
The North American east coast bush was adopted in Slavic countries. Now improved horticulture varieties have been returned.

 

[cjm]

significantly increased testosterone and luteinizing hormone (LH) levels

Word to the wise, elevated LH is perhaps a causative factor in Alzheimer's disease: "the protective effect of smoking and ibuprofen for Alzheimer’s disease is caused through LH suppression." Sci-Hub | The evolution of aging: a new approach to an old problem of biology. Medical Hypotheses, 51(3), 179–221 | 10.1016/S0306-9877(98)90079-2

Although, your next reference contradicts the increase, if reversed means what I think it does in context: "In addition, the levels of gonadotropins, including luteinizing hormone (LH) and follicle stimulating hormone (FSH), were reversed by C3G."

The gonadotropins, LH/FSH, are a primitive, probably very early in evolution, means of ramping up T production. Men don't want to rely on them, see the Alzheimer's link.

Here's the full study: Sci-Hub | Cyanidin-3-O-glucoside protects against cadmium-induced dysfunction of sex hormone secretion via the regulation of hypothalamus-pituitary-gonadal axis in male pubertal mice. Food and Chemical Toxicology | 10.1016/j.fct.2019.04.033

I have edited this post a bunch and had previously said C3G looked dope, but I don't think I would mess with it now. It is definitely working per se, increasing T as you and others are reporting androgenic effects, but it does not provide a fair bargain in my opinion -- the ride is not worth the cost of admission in other words.

Relative to controls, both FSH and LH were increased:

 

[Ras]

Word to the wise, elevated LH is perhaps a causative factor in Alzheimer's disease: "the protective effect of smoking and ibuprofen for Alzheimer’s disease is caused through LH suppression." Sci-Hub | The evolution of aging: a new approach to an old problem of biology. Medical Hypotheses, 51(3), 179–221 | 10.1016/S0306-9877(98)90079-2

Otherwise, this looks pretty dope

Melatonin also has this effect.

 

[cjm]

Melatonin also has this effect.

Yes. Jeff Bowles fan? His body of work is nuts. He's who learned me about the LH-AD connection.

 

[Mauritio]

Word to the wise, elevated LH is perhaps a causative factor in Alzheimer's disease: "the protective effect of smoking and ibuprofen for Alzheimer’s disease is caused through LH suppression." Sci-Hub | The evolution of aging: a new approach to an old problem of biology. Medical Hypotheses, 51(3), 179–221 | 10.1016/S0306-9877(98)90079-2

Although, your next reference contradicts the increase, if reversed means what I think it does in context: "In addition, the levels of gonadotropins, including luteinizing hormone (LH) and follicle stimulating hormone (FSH), were reversed by C3G."

The gonadotropins, LH/FSH, are a primitive, probably very early in evolution, means of ramping up T production. Men don't want to rely on them, see the Alzheimer's link.

Here's the full study: Sci-Hub | Cyanidin-3-O-glucoside protects against cadmium-induced dysfunction of sex hormone secretion via the regulation of hypothalamus-pituitary-gonadal axis in male pubertal mice. Food and Chemical Toxicology | 10.1016/j.fct.2019.04.033

I have edited this post a bunch and had previously said C3G looked dope, but I don't think I would mess with it now. It is definitely working per se, increasing T as you and others are reporting androgenic effects, but it does not provide a fair bargain in my opinion -- the ride is not worth the cost of admission in other words.

Relative to controls, both FSH and LH were increased:

View attachment 61476

Not taking C3G because there is "perhaps" a correlation with LH and alzheimers is pretty confusing.
Your hypothesis would make sense if it was known that there is a causal relationship (not just a correlation) between LH and alzheimers and at the same time C3G would only work through increasing LH, which it obviously does not. The small increase in LH is such a small part of its over all effects, that it seems kind of random to me to focus on that.

Plus on top of that C3G has actually been shown to treat / help with alzheimers, so avoiding it because of alzheimers risk makes not a lot of sense to me.

"Taken together, these results demonstrated that Cy3G can rescue the cognitive impairments that are induced by Aβ via the modulation of GSK-3β/tau, suggesting a potential therapeutic role of Cy3G in AD."
- Protective effect of cyanidin 3-O-glucoside on beta-amyloid peptide-induced cognitive impairment in rats - PubMed

"However, there have been no reports on whether C3G can regulate the M1/M2 shift in an Alzheimer's disease model.
... we confirmed that C3G could regulate microglial polarization by activating PPARγ and eliminating accumulated β-amyloid by enhancing Aβ42 phagocytosis through the upregulation of TREM2."
- Cyanidin-3-O-Glucoside Regulates the M1/M2 Polarization of Microglia via PPARγ and Aβ42 Phagocytosis Through TREM2 in an Alzheimer's Disease Model - PubMed

"C3G administration mitigated tau phosphorylation and improved synaptic function and plasticity by upregulating the expression of synapse-associated proteins synaptophysin and postsynaptic density protein-95. Although the potential of C3G in the APPswe/PS1ΔE9 mouse models has not yet been reported, oral administration of the C3G is shown to protect the brain and improve cognitive behavior."
- Cyanidin-3-O-glucoside protects the brain and improves cognitive function in APPswe/PS1ΔE9 transgenic mice model - PubMed

"These findings not only enable a comprehensive understanding of the inhibitory effect of Cy-3G on Aβ40 fibrillogenesis, but also allow the identification of a valuable dietary ingredient that possesses great potential to be developed into functional foods to alleviate AD.
- Cyanidin-3-O-glucoside inhibits Aβ40 fibrillogenesis, disintegrates preformed fibrils, and reduces amyloid cytotoxicity - PubMed

 

[Mauritio]

This study shows a strong performance enhancing effect of C3G :
it lowered lactate and increased exercise time to exhaustion by about 65% :

"Cy3G-administered mice did not get exhausted as fast as the control group as shown by the increased time to exhaustion (230 s  vs. 377 s, P = 0.02)."

The biceps femoris weight of the mice taking C3G was 65% heavier as well, compared to the control, so there was some hypertrophy going on I suppose.

It also increased ATP and UCP3 strongly in the in vitro part of the study:

"Cy3G increased the intracellular adenosine triphosphate (ATP) production in comparison to the lactate-treated control (87% vs 104%, P < 0.01)."
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357948/




Another study showing strong UCP1 increase in vivo.

"The expression of Ucp1 in the C3G-treated mice was 3.82 times and 3.06 times higher than those in the two control groups (Figure 1B,C). These results are consistent with our previous research results [4,17], further demonstrating C3G-induced upregulation of Ucp1 mRNA expression, both in vitro and in vivo."
- Cyanidin-3-O-glucoside Regulates the Expression of Ucp1 in Brown Adipose Tissue by Activating Prdm16 Gene

 

[cjm]

Not taking C3G because there is "perhaps" a correlation with LH and alzheimers is pretty confusing.
Your hypothesis would make sense if it was known that there is a causal relationship (not just a correlation) between LH and alzheimers and at the same time C3G would only work through increasing LH, which it obviously does not. The small increase in LH is such a small part of its over all effects, that it seems kind of random to me to focus on that.

Plus on top of that C3G has actually been shown to treat / help with alzheimers, so avoiding it because of alzheimers risk makes not a lot of sense to me.

"Taken together, these results demonstrated that Cy3G can rescue the cognitive impairments that are induced by Aβ via the modulation of GSK-3β/tau, suggesting a potential therapeutic role of Cy3G in AD."
- Protective effect of cyanidin 3-O-glucoside on beta-amyloid peptide-induced cognitive impairment in rats - PubMed

"However, there have been no reports on whether C3G can regulate the M1/M2 shift in an Alzheimer's disease model.
... we confirmed that C3G could regulate microglial polarization by activating PPARγ and eliminating accumulated β-amyloid by enhancing Aβ42 phagocytosis through the upregulation of TREM2."
- Cyanidin-3-O-Glucoside Regulates the M1/M2 Polarization of Microglia via PPARγ and Aβ42 Phagocytosis Through TREM2 in an Alzheimer's Disease Model - PubMed

"C3G administration mitigated tau phosphorylation and improved synaptic function and plasticity by upregulating the expression of synapse-associated proteins synaptophysin and postsynaptic density protein-95. Although the potential of C3G in the APPswe/PS1ΔE9 mouse models has not yet been reported, oral administration of the C3G is shown to protect the brain and improve cognitive behavior."
- Cyanidin-3-O-glucoside protects the brain and improves cognitive function in APPswe/PS1ΔE9 transgenic mice model - PubMed

"These findings not only enable a comprehensive understanding of the inhibitory effect of Cy-3G on Aβ40 fibrillogenesis, but also allow the identification of a valuable dietary ingredient that possesses great potential to be developed into functional foods to alleviate AD.
- Cyanidin-3-O-glucoside inhibits Aβ40 fibrillogenesis, disintegrates preformed fibrils, and reduces amyloid cytotoxicity - PubMed

I said perhaps a causation.

Gonadotropins are not a small part of C3G's effects, they are the reason for the increase in androgens.

The studies you present as refutation of my hypothesis do not address gonadotropins but beta amyloid (the "tangled" fibrils mistakenly thought to be the cause of Alzheimer's rather than just a symptom)

 

[Mauritio]

I said perhaps a causation.

Gonadotropins are not a small part of C3G's effects, they are the reason for the increase in androgens.

The studies you present as refutation of my hypothesis do not address gonadotropins but beta amyloid (the "tangled" fibrils mistakenly thought to be the cause of Alzheimer's rather than just a symptom)

Yep and thats a big perhaps.

lol did you even read this thread. They are not "the" reason for the increase in androgens. If there is one reason (and there isnt just one) it is C3G's effect on steroidogenic enzymes, which is literally in the title of this thread.

Wrong again. My point was not about LH but about C3G. And its pretty reducionistic to assume C3G only increases LH and does nothing else. I know you will say you did not say this, but this is basically what youre reducing C3G to.
What I am arguing is even if there was an effect of LH and C3G on alzheimers it is more down countered by C3G's anti-inflammatory and neuroprotective effects, which is coroborated by the fact that animals in alzheimers models experience a reduction in their symptoms.

 

[Dave Clark]

While you guys hash this out, I know I am going to continue consuming elderberries, dark fruit, red sorghum, black rice, etc., since there are other benefits, whether considered ancillary or not, that are important for immune function and other antioxidant reasons.

 

[martybyrde]

still going strong with the elderberry syrup. Libido, mood, energy still great. I have a confounding variable with regards to its gut effects so I can’t say if it’s really making me more regular.

 

[Mauritio]

Today was the first day in a week that i didnt drink elderberry juice and I felt pretty lethargic and low dopamine, might be a coincidence, but Ill get back to drinking it tomorrow...
Anybody else took it for a while and then stopped?
The energy promoting effects are quite obvious now that I quit , or maybe I just had a bad day, not sure.

 

[martybyrde]

Haven’t quit yet, but reduced the dose to just one tsp a day. Didn’t feel any worse

 

[Mauritio]

Cool.
I noticed that elerberry juice helped me sleep at least in 3 occasions, 1 time it didnt work. Which is interesting because it does have an energizing effect when i take it in the morning. So it seems to have adaptogenic qualities.
On the other hand peat said that falling asleep is an energy intensive process, so energizing migth actually help me to fall asleep.