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

[Mauritio]

Through reading about polyphenols I discovered this interesting compound that possibly has some interesting effects. It seems to boost Progesterone,Pregnenolone and Testosterone and various steroidogenic enzymes, especially the rate limiting enzyme StAR (hence the title). It also increases the number of androgen receptors in one study.
It also increases the anti-aging gene klotho and has an anti-inflammatory effect via COX-2.

1. "...cyanidin-3-O-glucoside (C3G) and its main metabolite protocatechuic acid (PCA) significantly increased testosterone and luteinizing hormone (LH) levels in the serum of rats, and improved sperm quality."
- Induction of reproductive injury by bisphenol A and the protective effects of cyanidin-3-O-glucoside and protocatechuic acid in rats - PubMed

2. "...C3G and PCA significantly up-regulated the gene expressions of Star, Cyp11a1, Cyp17a1, Cyp19a1, Cyp7a1, Hsd3b1, Hsd3b2, Hsd17b3, Scrab1, and Ass1 in testicular. In Leydig cells"
- Induction of reproductive injury by bisphenol A and the protective effects of cyanidin-3-O-glucoside and protocatechuic acid in rats - PubMed

3. " Interestingly, C3G improved the expression of LH and FSH receptor in the testis in mice exposed to Cd. Furthermore, C3G activated the signaling pathway related to the synthesis of testosterone processing."
- 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 - PubMed


4. "The results demonstrated that all four kinds of anthocyanins can inhibit ROS generation, alleviate mitochondrial membrane potential damage, and contribute to increased testosterone. Among them, Cy-3,5-diglu with diglycoside performed best on antioxidative ability and improved cell dysfunction and upregulated the expression of the steroidogenic acute regulatory protein (StAR). "
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952726/

5. Again it increases StAR but also CYP11A1 which converts cholesterol into pregnenolone (Cholesterol side-chain cleavage enzyme - Wikipedia) and 3bHSD which increases Progesterone.
"After being cultured in a medium containing C3G and Pb, R2C cells exhibited an increase in progesterone concentration compared with the Pb treatment, as a result of up-regulation of the expression of the steroidogenic enzymes steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) and cytochrome P450 enzyme cholesterol side chain cleavage enzyme (CYP11A1).
- https://www.researchgate.net/public...drial_function_in_Pb-exposed_rat_leydig_cells


6. Helps against heat stress in testicles
"It was found that C3G and PCA restored the external diameter and thickness, and alleviated atrophy and vacuolation of seminiferous tubules. Simultaneously, C3G and PCA enhanced testicular heat stress tolerance through reducing superfluous eIF2α phosphorylation and stress granule formation."
- https://www.researchgate.net/public...leviate_heat_stress-induced_testicular_damage

7. It lowers weight gain on a high fat diet and increases klotho more than 3 fold.
"... associated with increased expression of genes that encode FGFR1 and β-klotho (>3-fold, P < 0.05)"
- Dietary Cyanidin-3-Glucoside Attenuates High-Fat-Diet-Induced Body-Weight Gain and Impairment of Glucose Tolerance in Mice via Effects on the Hepatic Hormone FGF21 - PubMed

8. It did not have a significant effect on hormones in this study, but more importantly it increased the number of androgen receptors, which is even better since you dont have the danger of aromatization that you would get from increased Testosterone.
- Cyanidin-3- O-glucoside at Low Doses Protected against 3-Chloro-1,2-propanediol Induced Testis Injury and Improved Spermatogenesis in Male Rats - PubMed

9. It lowers serotonin by about 30% in platelets and protects against thrombosis on a HFD.
- Anthocyanin Cyanidin-3-Glucoside Attenuates Platelet Granule Release in Mice Fed High-Fat Diets - PubMed


Now you might wonder where do I get this stuff from? Nature has you covered.
Blackberries are considered a major source of C3G with about a 150mg/100g, BUT out of all foods by far the most C3G has black elderberry with about 800mg/100g! (Showing all foods in which the polyphenol Cyanidin 3-O-glucoside is found - Phenol-Explorer).

So the easiest and cheapest way to get C3G is probably through elderberry juice, which is widely available.
Even better, the most androgenic anthocyanin from study 4 is also contained in elderberry, just less concentrated.
Other foods than those two barely contain C3G, the third best option are black grapes with about 19mg/100g.
So black- and elderberries are the way to go.

Has anybody tried elderberry juice?

 

[Charger]

$10 for a 16oz bottle of elderberry juice, better be like roids in a bottle.

 

[Mauritio]

$10 for a 16oz bottle of elderberry juice, better be like roids in a bottle.

Youre living in the wrong country mate I get 330ml for 2.5€ . Still not cheap but I guess you dont drink that stuff in OJ-amounts.
- dm-drogerie markt - dauerhaft günstig online kaufen

 

[GTW]

C3g supplements often are black rice extracts.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598678/

 

[Mauritio]

C3g supplements often are black rice extracts.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598678/

The variation is insane and still far below black elderberry.

"Finally, black rice has the highest recorded TAC of all the coloured rice samples studied, with an average between 79.5 to 5101 mg anthocyanins/kg dry kernel weight [28,50,52,53,54,55]. "

 

[Mauritio]

It decreases NAFLD and NLRP3 inflammosome (implicated in hair loss) by removing damaged mitochondria (mitophagy) via PINK1.
PINK1 is able to resuce dopamine neurons in PD so C3G should be helpful for that as well.

- Cyanidin-3-O-glucoside improves non-alcoholic fatty liver disease by promoting PINK1-mediated mitophagy in mice - PubMed

- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702004/

 

[GTW]

The variation is insane and still far below black elderberry.

"Finally, black rice has the highest recorded TAC of all the coloured rice samples studied, with an average between 79.5 to 5101 mg anthocyanins/kg dry kernel weight [28,50,52,53,54,55]. "

Read the details. The values listed for specific rice varieties. Not unpredictable variation.
However, you can buy Organic dried elderberries or powder for reasonable prices.
Does smell a bit skunky.

 

[Mauritio]

Read the details. The values listed for specific rice varieties. Not unpredictable variation.
However, you can buy Organic dried elderberries or powder for reasonable prices.
Does smell a bit skunky.

Why not just elderberry juice?

 

[Mauritio]

So, I looked at a few studies and the HED ranged from 750-6000mg per day, with most studies using 3000mg.
750 mg equates to 100g of elderberries or elderberry juice, assuming the juice has a similar C3G conten, so it is pretty doable.
I would take these dosage recommendations with a grain of salt anyway, because the C3G content varies widely depending on the source. This is more to show that these dosages are achievable via food intake .

Alternatively, there is also elderberry extract as a supplement.

 

[GTW]

Dried elderberry dose would be much lower qty and probably lower cost.
Plus, often juice doesn't include the skin which typically has large concentration of pigment/cyanide. Maybe powder cyanidin concentrate is made from skin/pomace left over from juicing?

 

[Osukhan]

Cyanidin 3-Glucoside Capsules | 125mg | Black Rice Extract | Oryza sativa | Metabolic, Vision, & Cognitive Support

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i always get ads from this brand
didnt realize it had some androgen benefits

 

[Mauritio]

In this study they show that feeding mice and HED of just 300mg of C3G increases UCP1 by more than 3 fold and UCP2 by 2.5 fold. Mice exhibited therefore less weight gain on a high fat diet via increased energy expenditure (almost 20% increase at night)

- A dietary anthocyanin cyanidin-3-O-glucoside binds to PPARs to regulate glucose metabolism and insulin sensitivity in mice - Communications Biology

 

[Mauritio]

Dried elderberry dose would be much lower qty and probably lower cost.
Plus, often juice doesn't include the skin which typically has large concentration of pigment/cyanide. Maybe powder cyanidin concentrate is made from skin/pomace left over from juicing?

Thats a good point on the dried elderberries, there also realtively cheap.

Yeah thats true, juice might have alittle less anthocyanins. No idea, thb. Probabyl depends on manufactuerer /extract ,etc.

BTW elderberry has a long history in cecltic and germanic medicine. It is also called "herrgottsapotheke" which means pharmacy of the lord/god.

 

[Mauritio]

Cyanidin 3-Glucoside Capsules | 125mg | Black Rice Extract | Oryza sativa | Metabolic, Vision, & Cognitive Support

Nootropics Depot sells the best nootropic powders and capsules online. We offer pure nootropics and dietary supplements at the best prices. Shop nootropic stacks today. Take 10% off your order when you join our newsletter and enjoy free shipping on domestic orders over $50 or international...

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i always get ads from this brand
didnt realize it had some androgen benefits

ND is reputable brand. It seems pretty pricy though, given that you can get the content of one capsule from about 20g of elderberries and even less if what @GTW says is true and you use dried elderberries.

But one of the reviews sticks out:

"Eliminated bloat and discomfort
I never take the time to write reviews but this is a rather life-changing experience for me that I had to share in hopes that others benefit from seeing it. I got this for its body recomp effects and it does a great job there. Where it shines is how it has removed all gastrointestinal discomfort, bloat, belching, etc. I’ve dealt with ongoing issues for about 6 years where I was always bloated, constantly burping, heartburn, hiccups, etc. I’ve gone to several doctors and was given the traditional treatment of Prilosec or similar. I started with 1 pill of 3CG twice a day with a meal which was a lot to take at first as it was energizing but also seemed to lower my blood glucose levels a lot since I already have good levels there. I got used to it over 2-3 weeks, skipping a day here and there. At some point, I started taking 2 per meal and maxing at 4 pills/day which is 2 servings. All my gastrointestinal issues completely disappeared within 2-3 days and have not come back. I did not buy this with the intent to address stomach issues as I was unaware that it’s capable of helping in this area. I’ve bought thousands of dollars worth of supplements from ND and they’ve all been great and served their purpose. This one is honestly life changing for me personally. Not having to deal with bloat, stomach issues.. being able to breathe fully due to lack of bloat is something I have not experienced in 6 years till now. I can’t recommend this enough for anyone that has these types of pesky issues. I hope it works for others the same way it has for me."

 

[Mauritio]

C3G and other cyanines seem to inhibit MAO A and B ( as do many polyphenols btw!).
Im just not sure if that has any effect in reasonable dosages.

"When compared to known selective inhibitors, MAO A inhibition by anthocyanidins was 4000-fold weaker than that achievedby clorgyline and MAO B inhibition was 200-fold weaker compared to R-(−)-deprenyl. Proanthocyanidins B1 and B2 displayedonly minimal enzyme inhibitory effects. In view of anthocyanins’and proanthocyanidins’ instability in the intestinal environment[47–49], the role of phenolic acidmetabolites was also addressed forMAO A. To judge by the present in vitro data, however, their activityis negligible (IC50 values >3.9 mM) which further emphasizes theneed to examine the bioavailability of parent compounds"

- Berry anthocyanins and their aglycons inhibit monoamine oxidases A and B - PubMed

 

[GTW]

Aronia aka black chokeberry tastes good.
I buy 1 lb dry for about $20.
Recent catalog from Pacific Botanicals lists dried elderberry berries, $31/lb.

 

[Osukhan]

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ive used this product pretty regularly over the last year, im a big Joel Greene fan

 

[GTW]

The testimony to C3G for bloating GI dysfunction convinced me to add 30 cc dried elderberries to the black rice already cooking with a chicken thigh. Good flavor, elderberries retained pleasant crunch.

 

[Dave Clark]

Regarding elderberry, if anyone has the place, they are super easy to grow. I put in elderberry bushes 25 years ago, same plants, no replanting. No spraying necessary, just prune down to the ground in the spring {this prevents them from turning into trees}, and they will grow back to about 6 ft and produce. I got about three lbs of dried elderberries, which is a good harvest from about 4 bushes. To make an elderberry syrup, use 2 cups dried elderberry to 4 cups of water boil then simmer for 2 hours, then turn off burner and let sit for a few more hours until cool. Then strain and mix with about a cup of raw honey. Syrup comes out thick and dark, with all the cyanidins you want, for just the price of the honey and cost of the initial plants [if you know someone who has them, they root and grow easy from cuttings}.

 

[GTW]

Regarding elderberry, if anyone has the place, they are super easy to grow. I put in elderberry bushes 25 years ago, same plants, no replanting. No spraying necessary, just prune down to the ground in the spring {this prevents them from turning into trees}, and they will grow back to about 6 ft and produce. I got about three lbs of dried elderberries, which is a good harvest from about 4 bushes. To make an elderberry syrup, use 2 cups dried elderberry to 4 cups of water boil then simmer for 2 hours, then turn off burner and let sit for a few more hours until cool. Then strain and mix with about a cup of raw honey. Syrup comes out thick and dark, with all the cyanidins you want, for just the price of the honey and cost of the initial plants [if you know someone who has them, they root and grow easy from cuttings}.

I have black currants, equally hardy and prolific, another source of C3G. This spring I will find elderberries to grow.